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New lipid-lowering drug class slashes LDL in HoFH patients
Evinacumab, the first agent from a new class of lipid-lowering drugs, showed a “remarkable” and unprecedented level of LDL-cholesterol lowering in a pivotal trial with 65 patients with homozygous familial hypercholesterolemia.
Monthly intravenous infusions of evinacumab cut LDL cholesterol levels by an average of 135 mg/dL from baseline, a 47% mean reduction, after 24 weeks of treatment in 43 homozygous familial hypercholesterolemia (HoFH) patients, Frederick Raal, MBChB, said on March 30 in a video presentation of his research at the joint scientific sessions of the American College of Cardiology and the World Heart Federation, which was presented online this year. ACC organizers chose to present parts of the meeting virtually after COVID-19 concerns caused them to cancel the meeting.
Evinacumab is a human monoclonal antibody inhibitor of angiopoietin-like 3, a liver protein that boosts levels of LDL cholesterol and triglycerides (TG).
Another notable effect of the novel agent was that it was equally effective in the roughly one-third of patients with a minimal residual level of LDL receptor activity, patients know as having “null/null” mutations. “For the first time, we see HoFH patients getting to [lipid] targets that we never thought would be possible,” said Dr. Raal, professor and head of endocrinology and metabolism at the University of Witwatersrand in Johannesburg, South Africa. “This works in patients without residual LDL receptor function.” The drug was also generally very well tolerated, he said, causing no treatment-related serious adverse events during the brief treatment period of 24 weeks.
“One of the major, remarkable findings in this study was the effect on null/null patients,” which contrasts with the effects of other, more established drugs for treating dyslipidemia like statins and PCSK9 inhibitors, which work by increasing the number of LDL receptors on cells. The demonstrated efficacy and safety of evinacumab in null/null patients “is a definite advance,” commented Anne C. Goldberg, MD, a lipidologist and professor of medicine at Washington University in St. Louis.
The placebo-controlled trial randomized patients at 30 sites in 11 countries who were at least 12 years old and had documented mutations in both of their LDL receptor genes and a serum level of LDL cholesterol that was at least 500 mg/dL on no treatment. Patients averaged about 40 years of age; about 30% had null/null mutations, more than 90% were on statin treatment, and about three-quarters were receiving regular treatment with a PCSK9 inhibitor. At baseline, LDL cholesterol levels averaged about 250 mg/dL.
The study’s primary endpoint was the between-group percentage change in LDL cholesterol level after 24 weeks, which fell by 47% from baseline with evinacumab treatment and increased by an average of 2% among 22 patients who received placebo injections; so evinacumab cut this measure by 49%, compared with placebo after 24 weeks, a statistically significant difference. A cut of baseline LDL cholesterol by at least 50% occurred in 56% of the evinacumab-treated patients and in 5% of controls.
In addition to its LDL reduction, another notable effect of evinacumab was that it trimmed baseline triglyceride levels by half, consistent with prior reports of the drug’s effect on this measure, although average triglyceride levels in the enrolled patients fell within the normal range prior to treatment.
Evinacumab “will probably be very effective in treating patients with hypertriglyceridemia; those studies are ongoing,” noted Dr. Raal. But, he added, “this drug will probably be reserved for severe” dyslipidemia cases, not for “the garden variety of moderate hypertriglyceridemia or hypercholesterolemia.”
Evinacumab “may be a fairly broad-spectrum lipid-lowering drug, but it should be reserved for severe cases,” agreed Dirk Blom, MBChB, head of lipidology at the University of Capetown, South Africa. “This will likely remain a fairly expensive drug, and we wouldn’t want to use it across the board, but for difficult to treat patients with either severe hypercholesterolemia or hypertriglyceridemia, I think this will have very significant advantages,” he commented.
“Drugs that reduce triglycerides by large amounts may prove to have cardiovascular disease benefits, but that remains to be proven in large, long-term outcome trials,” commented Deepak Bhatt, MD, professor of medicine at Harvard Medical School and executive director of interventional cardiology programs at Brigham and Women’s Hospital, both in Boston. “But for right now, for most patients with more common forms of elevated LDL cholesterol, the treatment options include statins, ezetimibe [Zetia], and PCSK9 inhibitors, and for more common levels of elevated triglycerides, it’s icosapent ethyl [Vascepa],” Dr. Bhatt said.
The study was sponsored by Regeneron, the company developing evinacumab and which is partially owned by Sanofi. Dr. Raal has received personal fees and/or research funding from Regeneron, Sanofi Aventis, Amgen, and The Medicines Company. Dr. Goldberg has received research funding and/or consulting fees from Regeneron and Sanofi, Akcea, Amarin, Amgen, Esperion, Ionis, Merck, Novartis, and Pfizer. Dr. Blom has been a consultant to and/or received research funding from Regeneron, Sanofi, Aegerium, Akcea, Amgen, Amryt, AstraZeneca, Eli Lilly, Esperion, Gemphire, MSD, and Novo Nordisk. Dr. Bhatt has received research funding from many companies including Regeneron and Sanofi.
SOURCE: Raal F. ACC 20. Abstract 411-12.
Evinacumab, the first agent from a new class of lipid-lowering drugs, showed a “remarkable” and unprecedented level of LDL-cholesterol lowering in a pivotal trial with 65 patients with homozygous familial hypercholesterolemia.
Monthly intravenous infusions of evinacumab cut LDL cholesterol levels by an average of 135 mg/dL from baseline, a 47% mean reduction, after 24 weeks of treatment in 43 homozygous familial hypercholesterolemia (HoFH) patients, Frederick Raal, MBChB, said on March 30 in a video presentation of his research at the joint scientific sessions of the American College of Cardiology and the World Heart Federation, which was presented online this year. ACC organizers chose to present parts of the meeting virtually after COVID-19 concerns caused them to cancel the meeting.
Evinacumab is a human monoclonal antibody inhibitor of angiopoietin-like 3, a liver protein that boosts levels of LDL cholesterol and triglycerides (TG).
Another notable effect of the novel agent was that it was equally effective in the roughly one-third of patients with a minimal residual level of LDL receptor activity, patients know as having “null/null” mutations. “For the first time, we see HoFH patients getting to [lipid] targets that we never thought would be possible,” said Dr. Raal, professor and head of endocrinology and metabolism at the University of Witwatersrand in Johannesburg, South Africa. “This works in patients without residual LDL receptor function.” The drug was also generally very well tolerated, he said, causing no treatment-related serious adverse events during the brief treatment period of 24 weeks.
“One of the major, remarkable findings in this study was the effect on null/null patients,” which contrasts with the effects of other, more established drugs for treating dyslipidemia like statins and PCSK9 inhibitors, which work by increasing the number of LDL receptors on cells. The demonstrated efficacy and safety of evinacumab in null/null patients “is a definite advance,” commented Anne C. Goldberg, MD, a lipidologist and professor of medicine at Washington University in St. Louis.
The placebo-controlled trial randomized patients at 30 sites in 11 countries who were at least 12 years old and had documented mutations in both of their LDL receptor genes and a serum level of LDL cholesterol that was at least 500 mg/dL on no treatment. Patients averaged about 40 years of age; about 30% had null/null mutations, more than 90% were on statin treatment, and about three-quarters were receiving regular treatment with a PCSK9 inhibitor. At baseline, LDL cholesterol levels averaged about 250 mg/dL.
The study’s primary endpoint was the between-group percentage change in LDL cholesterol level after 24 weeks, which fell by 47% from baseline with evinacumab treatment and increased by an average of 2% among 22 patients who received placebo injections; so evinacumab cut this measure by 49%, compared with placebo after 24 weeks, a statistically significant difference. A cut of baseline LDL cholesterol by at least 50% occurred in 56% of the evinacumab-treated patients and in 5% of controls.
In addition to its LDL reduction, another notable effect of evinacumab was that it trimmed baseline triglyceride levels by half, consistent with prior reports of the drug’s effect on this measure, although average triglyceride levels in the enrolled patients fell within the normal range prior to treatment.
Evinacumab “will probably be very effective in treating patients with hypertriglyceridemia; those studies are ongoing,” noted Dr. Raal. But, he added, “this drug will probably be reserved for severe” dyslipidemia cases, not for “the garden variety of moderate hypertriglyceridemia or hypercholesterolemia.”
Evinacumab “may be a fairly broad-spectrum lipid-lowering drug, but it should be reserved for severe cases,” agreed Dirk Blom, MBChB, head of lipidology at the University of Capetown, South Africa. “This will likely remain a fairly expensive drug, and we wouldn’t want to use it across the board, but for difficult to treat patients with either severe hypercholesterolemia or hypertriglyceridemia, I think this will have very significant advantages,” he commented.
“Drugs that reduce triglycerides by large amounts may prove to have cardiovascular disease benefits, but that remains to be proven in large, long-term outcome trials,” commented Deepak Bhatt, MD, professor of medicine at Harvard Medical School and executive director of interventional cardiology programs at Brigham and Women’s Hospital, both in Boston. “But for right now, for most patients with more common forms of elevated LDL cholesterol, the treatment options include statins, ezetimibe [Zetia], and PCSK9 inhibitors, and for more common levels of elevated triglycerides, it’s icosapent ethyl [Vascepa],” Dr. Bhatt said.
The study was sponsored by Regeneron, the company developing evinacumab and which is partially owned by Sanofi. Dr. Raal has received personal fees and/or research funding from Regeneron, Sanofi Aventis, Amgen, and The Medicines Company. Dr. Goldberg has received research funding and/or consulting fees from Regeneron and Sanofi, Akcea, Amarin, Amgen, Esperion, Ionis, Merck, Novartis, and Pfizer. Dr. Blom has been a consultant to and/or received research funding from Regeneron, Sanofi, Aegerium, Akcea, Amgen, Amryt, AstraZeneca, Eli Lilly, Esperion, Gemphire, MSD, and Novo Nordisk. Dr. Bhatt has received research funding from many companies including Regeneron and Sanofi.
SOURCE: Raal F. ACC 20. Abstract 411-12.
Evinacumab, the first agent from a new class of lipid-lowering drugs, showed a “remarkable” and unprecedented level of LDL-cholesterol lowering in a pivotal trial with 65 patients with homozygous familial hypercholesterolemia.
Monthly intravenous infusions of evinacumab cut LDL cholesterol levels by an average of 135 mg/dL from baseline, a 47% mean reduction, after 24 weeks of treatment in 43 homozygous familial hypercholesterolemia (HoFH) patients, Frederick Raal, MBChB, said on March 30 in a video presentation of his research at the joint scientific sessions of the American College of Cardiology and the World Heart Federation, which was presented online this year. ACC organizers chose to present parts of the meeting virtually after COVID-19 concerns caused them to cancel the meeting.
Evinacumab is a human monoclonal antibody inhibitor of angiopoietin-like 3, a liver protein that boosts levels of LDL cholesterol and triglycerides (TG).
Another notable effect of the novel agent was that it was equally effective in the roughly one-third of patients with a minimal residual level of LDL receptor activity, patients know as having “null/null” mutations. “For the first time, we see HoFH patients getting to [lipid] targets that we never thought would be possible,” said Dr. Raal, professor and head of endocrinology and metabolism at the University of Witwatersrand in Johannesburg, South Africa. “This works in patients without residual LDL receptor function.” The drug was also generally very well tolerated, he said, causing no treatment-related serious adverse events during the brief treatment period of 24 weeks.
“One of the major, remarkable findings in this study was the effect on null/null patients,” which contrasts with the effects of other, more established drugs for treating dyslipidemia like statins and PCSK9 inhibitors, which work by increasing the number of LDL receptors on cells. The demonstrated efficacy and safety of evinacumab in null/null patients “is a definite advance,” commented Anne C. Goldberg, MD, a lipidologist and professor of medicine at Washington University in St. Louis.
The placebo-controlled trial randomized patients at 30 sites in 11 countries who were at least 12 years old and had documented mutations in both of their LDL receptor genes and a serum level of LDL cholesterol that was at least 500 mg/dL on no treatment. Patients averaged about 40 years of age; about 30% had null/null mutations, more than 90% were on statin treatment, and about three-quarters were receiving regular treatment with a PCSK9 inhibitor. At baseline, LDL cholesterol levels averaged about 250 mg/dL.
The study’s primary endpoint was the between-group percentage change in LDL cholesterol level after 24 weeks, which fell by 47% from baseline with evinacumab treatment and increased by an average of 2% among 22 patients who received placebo injections; so evinacumab cut this measure by 49%, compared with placebo after 24 weeks, a statistically significant difference. A cut of baseline LDL cholesterol by at least 50% occurred in 56% of the evinacumab-treated patients and in 5% of controls.
In addition to its LDL reduction, another notable effect of evinacumab was that it trimmed baseline triglyceride levels by half, consistent with prior reports of the drug’s effect on this measure, although average triglyceride levels in the enrolled patients fell within the normal range prior to treatment.
Evinacumab “will probably be very effective in treating patients with hypertriglyceridemia; those studies are ongoing,” noted Dr. Raal. But, he added, “this drug will probably be reserved for severe” dyslipidemia cases, not for “the garden variety of moderate hypertriglyceridemia or hypercholesterolemia.”
Evinacumab “may be a fairly broad-spectrum lipid-lowering drug, but it should be reserved for severe cases,” agreed Dirk Blom, MBChB, head of lipidology at the University of Capetown, South Africa. “This will likely remain a fairly expensive drug, and we wouldn’t want to use it across the board, but for difficult to treat patients with either severe hypercholesterolemia or hypertriglyceridemia, I think this will have very significant advantages,” he commented.
“Drugs that reduce triglycerides by large amounts may prove to have cardiovascular disease benefits, but that remains to be proven in large, long-term outcome trials,” commented Deepak Bhatt, MD, professor of medicine at Harvard Medical School and executive director of interventional cardiology programs at Brigham and Women’s Hospital, both in Boston. “But for right now, for most patients with more common forms of elevated LDL cholesterol, the treatment options include statins, ezetimibe [Zetia], and PCSK9 inhibitors, and for more common levels of elevated triglycerides, it’s icosapent ethyl [Vascepa],” Dr. Bhatt said.
The study was sponsored by Regeneron, the company developing evinacumab and which is partially owned by Sanofi. Dr. Raal has received personal fees and/or research funding from Regeneron, Sanofi Aventis, Amgen, and The Medicines Company. Dr. Goldberg has received research funding and/or consulting fees from Regeneron and Sanofi, Akcea, Amarin, Amgen, Esperion, Ionis, Merck, Novartis, and Pfizer. Dr. Blom has been a consultant to and/or received research funding from Regeneron, Sanofi, Aegerium, Akcea, Amgen, Amryt, AstraZeneca, Eli Lilly, Esperion, Gemphire, MSD, and Novo Nordisk. Dr. Bhatt has received research funding from many companies including Regeneron and Sanofi.
SOURCE: Raal F. ACC 20. Abstract 411-12.
REPORTING FROM ACC 2020
Alirocumab effective in homozygous FH
Alirocumab achieved a mean 63-mg/dL reduction in LDL cholesterol in the ODYSSEY HoFH study, the largest-ever randomized, placebo-controlled clinical trial of lipid-lowering in adults with homozygous familial hypercholesterolemia (HoFH), Dirk Blom, MD, said in a video presentation of his research during the joint scientific sessions of the American College of Cardiology and the World Heart Federation, which was presented online this year. ACC organizers chose to present parts of the meeting virtually after COVID-19 concerns caused them to cancel the meeting.
“We’re not getting most patients to goal, but we’re certainly getting them closer to goal. A lot of patients will still need further therapies that don’t rely on up-regulation of the LDL receptor, such as lipoprotein apheresis,” observed Dr. Blom, head of the division of lipidology at the University of Cape Town (South Africa).
Of the patients on alirocumab, 57%had at least a 30% reduction in LDL at 12 weeks, and 27% had a 50% reduction or more.
Alirocumab had salutary effects on other atherogenic lipids: roughly a 20% reduction from baseline in lipoprotein (a), a 23% decrease in apolipoprotein B, and a 25% reduction in non-HDL cholesterol.
Dr. Blom noted that, as is also the case for statins in HoFH, the LDL response to alirocumab in patients with this genetically complex disorder is more variable and generally weaker than in other hypercholesterolemic populations.
“We saw some patients getting up to 60%-70% LDL reduction in alirocumab, but a lot of patients getting much less,” he said.
Alirocumab was well tolerated in adults with HoFH, with the same favorable safety profile that’s been established in other patient populations.
Discussant Raul Santos, MD, commented that the ODYSSEY HoFH results are quite similar to those reported in patients with HoFH in an earlier study of evolocumab (Repatha), another PCSK9 inhibitor. The magnitude of LDL-lowering achieved with these biologic agents is such that, were treatment to start early in life, patients with HoFH might expect to experience an extra 10-15 years of life free of cardiovascular events.
“Certainly PCSK9 inhibitors should be the next step after statins and ezetimibe. They’re much less expensive and more available than apheresis,” said Dr. Santos, director of the lipid clinic at the Heart Institute of the University of São Paulo.
Since many patients with this rare disorder experience their first cardiovascular event in adolescence or young adulthood, Dr. Santos said, it’s very important to expand PCSK9 inhibitor therapy to the pediatric HoFH population. Two studies are ongoing in childlren.
The ODYSSEY HoFH trial was funded by Regeneron and Sanofi. Dr. Blom reported serving as a paid consultant to Sanofi, Akcea, Amgen, and Gemphire.
Alirocumab achieved a mean 63-mg/dL reduction in LDL cholesterol in the ODYSSEY HoFH study, the largest-ever randomized, placebo-controlled clinical trial of lipid-lowering in adults with homozygous familial hypercholesterolemia (HoFH), Dirk Blom, MD, said in a video presentation of his research during the joint scientific sessions of the American College of Cardiology and the World Heart Federation, which was presented online this year. ACC organizers chose to present parts of the meeting virtually after COVID-19 concerns caused them to cancel the meeting.
“We’re not getting most patients to goal, but we’re certainly getting them closer to goal. A lot of patients will still need further therapies that don’t rely on up-regulation of the LDL receptor, such as lipoprotein apheresis,” observed Dr. Blom, head of the division of lipidology at the University of Cape Town (South Africa).
Of the patients on alirocumab, 57%had at least a 30% reduction in LDL at 12 weeks, and 27% had a 50% reduction or more.
Alirocumab had salutary effects on other atherogenic lipids: roughly a 20% reduction from baseline in lipoprotein (a), a 23% decrease in apolipoprotein B, and a 25% reduction in non-HDL cholesterol.
Dr. Blom noted that, as is also the case for statins in HoFH, the LDL response to alirocumab in patients with this genetically complex disorder is more variable and generally weaker than in other hypercholesterolemic populations.
“We saw some patients getting up to 60%-70% LDL reduction in alirocumab, but a lot of patients getting much less,” he said.
Alirocumab was well tolerated in adults with HoFH, with the same favorable safety profile that’s been established in other patient populations.
Discussant Raul Santos, MD, commented that the ODYSSEY HoFH results are quite similar to those reported in patients with HoFH in an earlier study of evolocumab (Repatha), another PCSK9 inhibitor. The magnitude of LDL-lowering achieved with these biologic agents is such that, were treatment to start early in life, patients with HoFH might expect to experience an extra 10-15 years of life free of cardiovascular events.
“Certainly PCSK9 inhibitors should be the next step after statins and ezetimibe. They’re much less expensive and more available than apheresis,” said Dr. Santos, director of the lipid clinic at the Heart Institute of the University of São Paulo.
Since many patients with this rare disorder experience their first cardiovascular event in adolescence or young adulthood, Dr. Santos said, it’s very important to expand PCSK9 inhibitor therapy to the pediatric HoFH population. Two studies are ongoing in childlren.
The ODYSSEY HoFH trial was funded by Regeneron and Sanofi. Dr. Blom reported serving as a paid consultant to Sanofi, Akcea, Amgen, and Gemphire.
Alirocumab achieved a mean 63-mg/dL reduction in LDL cholesterol in the ODYSSEY HoFH study, the largest-ever randomized, placebo-controlled clinical trial of lipid-lowering in adults with homozygous familial hypercholesterolemia (HoFH), Dirk Blom, MD, said in a video presentation of his research during the joint scientific sessions of the American College of Cardiology and the World Heart Federation, which was presented online this year. ACC organizers chose to present parts of the meeting virtually after COVID-19 concerns caused them to cancel the meeting.
“We’re not getting most patients to goal, but we’re certainly getting them closer to goal. A lot of patients will still need further therapies that don’t rely on up-regulation of the LDL receptor, such as lipoprotein apheresis,” observed Dr. Blom, head of the division of lipidology at the University of Cape Town (South Africa).
Of the patients on alirocumab, 57%had at least a 30% reduction in LDL at 12 weeks, and 27% had a 50% reduction or more.
Alirocumab had salutary effects on other atherogenic lipids: roughly a 20% reduction from baseline in lipoprotein (a), a 23% decrease in apolipoprotein B, and a 25% reduction in non-HDL cholesterol.
Dr. Blom noted that, as is also the case for statins in HoFH, the LDL response to alirocumab in patients with this genetically complex disorder is more variable and generally weaker than in other hypercholesterolemic populations.
“We saw some patients getting up to 60%-70% LDL reduction in alirocumab, but a lot of patients getting much less,” he said.
Alirocumab was well tolerated in adults with HoFH, with the same favorable safety profile that’s been established in other patient populations.
Discussant Raul Santos, MD, commented that the ODYSSEY HoFH results are quite similar to those reported in patients with HoFH in an earlier study of evolocumab (Repatha), another PCSK9 inhibitor. The magnitude of LDL-lowering achieved with these biologic agents is such that, were treatment to start early in life, patients with HoFH might expect to experience an extra 10-15 years of life free of cardiovascular events.
“Certainly PCSK9 inhibitors should be the next step after statins and ezetimibe. They’re much less expensive and more available than apheresis,” said Dr. Santos, director of the lipid clinic at the Heart Institute of the University of São Paulo.
Since many patients with this rare disorder experience their first cardiovascular event in adolescence or young adulthood, Dr. Santos said, it’s very important to expand PCSK9 inhibitor therapy to the pediatric HoFH population. Two studies are ongoing in childlren.
The ODYSSEY HoFH trial was funded by Regeneron and Sanofi. Dr. Blom reported serving as a paid consultant to Sanofi, Akcea, Amgen, and Gemphire.
REPORTING FROM ACC 2020
Larger absolute rivaroxaban benefit in diabetes: COMPASS
In the COMPASS trial of patients with stable coronary or peripheral artery disease (PAD), the combination of aspirin plus rivaroxaban, 2.5 mg twice daily, provided a larger absolute benefit on cardiovascular endpoints — including a threefold greater reduction in all-cause mortality — in patients with diabetes compared with the overall population.
The results of the diabetes subset of the COMPASS trial were presented by Deepak Bhatt, MD, Brigham and Women’s Hospital Heart & Vascular Center, Boston, Massachusetts, on March 28 at the “virtual” American College of Cardiology 2020 Scientific Session (ACC.20)/World Congress of Cardiology (WCC). They were also simultaneously published online in Circulation.
“Use of dual pathway inhibition with low-dose rivaroxaban plus aspirin is particularly attractive in high-risk patients such as those with diabetes,” Bhatt concluded.
The COMPASS trial was first reported in 2017 and showed a new low dose of rivaroxaban (2.5-mg twice-daily; Xarelto, Bayer/Janssen Pharmaceuticals) plus aspirin, 100 mg once daily, was associated with a reduction in ischemic events and mortality and a superior net clinical benefit, balancing ischemic benefit with severe bleeding, compared with aspirin alone for secondary prevention in patients with stable atherosclerotic vascular disease.
But clinicians have been slow to prescribe rivaroxaban in this new and very large population.
“It’s been more than 2 years now since main COMPASS results, and there isn’t a sense that this therapy has really caught on,” chair of the current ACC session at which the diabetes subgroup results were presented, Hadley Wilson, MD, Sanger Heart and Vascular Institute, Charlotte, North Carolina, commented:
He asked Bhatt whether the diabetes subgroup may be “the tipping point that will make people aware of rivaroxaban and then that may trickle down to other patients.”
Bhatt said that he hoped that would be the case. “We as a steering committee of this trial could say the results were positive so rivaroxaban should now be used in everyone with stable coronary or peripheral arterial disease, but that is impractical and as you out point out it hasn’t happened,” he replied.
“In PAD/vascular medicine we have embraced this new therapy. In the broader cardiology world there are a lot of patients with stable coronary arterial disease at high ischemic risk who could take rivaroxaban, but its use is bound to be limited by it being a branded drug and the fact that there is a bleeding risk,” Bhatt explained.
“I think we need to identify patients with the highest ischemic risk and focus drugs such as these with a financial cost and a bleeding risk on those who most likely will derive the greatest absolute reduction in risk,” he said. “The PAD subgroup is one group where this is the case, and now we have shown the diabetes subgroup is another. And there is no incremental bleeding risk in this group over the whole population, so they get a much greater benefit without a greater risk. I hope this helps get rivaroxaban at the new lower dose used much more often.”
A total of 18,278 patients were randomly assigned to the combination of rivaroxaban and aspirin or aspirin alone in the COMPASS trial. Of these, 6922 had diabetes mellitus at baseline and 11,356 did not have diabetes.
Results from the current analysis show a consistent and similar relative risk reduction for benefit of rivaroxaban plus aspirin vs placebo plus aspirin in patients both with and without diabetes for the primary efficacy endpoint, a composite of cardiovascular death, myocardial infarction (MI), or stroke, with a hazard ratio of 0.74 for patients with diabetes and 0.77 for those without diabetes, the researchers report.
Because of the higher baseline risk in the diabetes subgroup, these patients had numerically larger absolute risk reductions with rivaroxaban than those without diabetes for the primary efficacy endpoint at 3 years (2.3% vs 1.4%) and for all-cause mortality (1.9% vs 0.6%).
These results translate into a number needed to treat (NNT) with rivaroxaban for 3 years to prevent one CV death, MI, or stroke of 44 for the diabetes group vs 73 for the nondiabetes group; the NNT to prevent one all-cause death was 54 for the diabetes group vs 167 for the nondiabetes group, the authors write.
Because the bleeding hazards were similar among patients with and without diabetes, the absolute net clinical benefit (MI, stroke, cardiovascular death, or bleeding leading to death or symptomatic bleeding into a critical organ) for rivaroxaban was “particularly favorable” in the diabetes group (2.7% fewer events in the diabetes group vs 1.0% fewer events in the nondiabetes group), they add.
Panelist at the ACC Featured Clinical Research session at which these results were presented, Jennifer Robinson, MD, University of Iowa College of Public Health, Iowa City, asked Bhatt how clinicians were supposed to decide which of the many new agents now becoming available for patients with stable coronary artery disease to prescribe first.
“We often forget about rivaroxaban when we’re thinking about what to add next for our secondary prevention patients,” she said. “You also led the REDUCE-IT trial showing benefit of icosapent ethyl, icosapent ethyl icosapent ethyl icosapent ethyl and there is also ezetimibe, PCSK9 inhibitors and SGLT2 inhibitors. For your patients with coronary disease who are already on a high dose statin which one of these would you add next?”
“That is what physicians need to ponder all the time,” Bhatt replied. “And when a patient has several risk factors that are not well controlled, I guess it’s all important. I go through a checklist with my patients and try and figure what they’re not on that could further reduce their risk.”
“In the COMPASS trial there was an overall positive result with rivaroxaban in the whole population. And now we have shown that patients with diabetes had an even greater absolute risk reduction. That pattern has also been seen with other classes of agents including the statins, PCSK9 inhibitors, and icosapent ethyl,” Bhatt noted.
“In patients with diabetes, I will usually target whatever is standing out most at that time. If their glycemic control is completely out of whack, then that is what I would focus on first, and these days often with a SGLT2 inhibitor or GLP-1 agonist. If the LDL was out of control, I would add ezetimibe or a PCSK9 inhibitor. If the triglycerides were high, I would add icosapent ethyl. If multiple things were out of control, I would usually focus on the number most out of kilter first and try not to forget about everything else.”
But Bhatt noted that the challenge with rivaroxaban is that there is no test of thrombosis risk that would prompt the physician to take action. “Basically, the doctor just has to remember to do it. In that regard I would consider whether patients are at low bleeding risk and are they still at high ischemic risk despite controlling other risk factors and, if so, then I would add this low dose of rivaroxaban.”
Another panel member, Sekar Kathiresan, MD, asked Bhatt whether he recommended using available scores to assess the bleeding/thrombosis risk/benefits of adding an antithrombotic.
Bhatt replied: “That’s a terrific question. I guess the right answer is that we should be doing that, but in reality I have to concede that I don’t use these scores. They have shown appropriate C statistics in populations, but they are not fantastic in individual patients.”
“I have to confess that I use the eyeball test. There is nothing as good at predicting future bleeding as past bleeding. So if a patient has had bleeding problems on aspirin alone I wouldn’t add rivaroxaban. But if a patient hasn’t bled before, especially if they had some experience of dual antiplatelet therapy, then they would be good candidates for a low vascular dose of rivaroxaban,” he said.
“It is not as easy as with other drugs as there is always a bleeding trade-off with an antithrombotic. There is no such thing as a free lunch. So patients need careful assessment when considering prescribing rivaroxaban and regular reassessment over time to check if they have had any bleeding,” he added.
The COMPASS study was funded by Bayer. Bhatt reports honoraria from Bayer via the Population Health Research Institute for his role on the COMPASS trial and other research funding from Bayer to the Brigham & Women’s Hospital.
American College of Cardiology 2020 Scientific Session (ACC.20)/World Congress of Cardiology (WCC). Abstract 20-LB-20544-ACC. Presented March 28, 2020.
Circulation. Published online March 28, 2020. Full text.
This article first appeared on Medscape.com.
In the COMPASS trial of patients with stable coronary or peripheral artery disease (PAD), the combination of aspirin plus rivaroxaban, 2.5 mg twice daily, provided a larger absolute benefit on cardiovascular endpoints — including a threefold greater reduction in all-cause mortality — in patients with diabetes compared with the overall population.
The results of the diabetes subset of the COMPASS trial were presented by Deepak Bhatt, MD, Brigham and Women’s Hospital Heart & Vascular Center, Boston, Massachusetts, on March 28 at the “virtual” American College of Cardiology 2020 Scientific Session (ACC.20)/World Congress of Cardiology (WCC). They were also simultaneously published online in Circulation.
“Use of dual pathway inhibition with low-dose rivaroxaban plus aspirin is particularly attractive in high-risk patients such as those with diabetes,” Bhatt concluded.
The COMPASS trial was first reported in 2017 and showed a new low dose of rivaroxaban (2.5-mg twice-daily; Xarelto, Bayer/Janssen Pharmaceuticals) plus aspirin, 100 mg once daily, was associated with a reduction in ischemic events and mortality and a superior net clinical benefit, balancing ischemic benefit with severe bleeding, compared with aspirin alone for secondary prevention in patients with stable atherosclerotic vascular disease.
But clinicians have been slow to prescribe rivaroxaban in this new and very large population.
“It’s been more than 2 years now since main COMPASS results, and there isn’t a sense that this therapy has really caught on,” chair of the current ACC session at which the diabetes subgroup results were presented, Hadley Wilson, MD, Sanger Heart and Vascular Institute, Charlotte, North Carolina, commented:
He asked Bhatt whether the diabetes subgroup may be “the tipping point that will make people aware of rivaroxaban and then that may trickle down to other patients.”
Bhatt said that he hoped that would be the case. “We as a steering committee of this trial could say the results were positive so rivaroxaban should now be used in everyone with stable coronary or peripheral arterial disease, but that is impractical and as you out point out it hasn’t happened,” he replied.
“In PAD/vascular medicine we have embraced this new therapy. In the broader cardiology world there are a lot of patients with stable coronary arterial disease at high ischemic risk who could take rivaroxaban, but its use is bound to be limited by it being a branded drug and the fact that there is a bleeding risk,” Bhatt explained.
“I think we need to identify patients with the highest ischemic risk and focus drugs such as these with a financial cost and a bleeding risk on those who most likely will derive the greatest absolute reduction in risk,” he said. “The PAD subgroup is one group where this is the case, and now we have shown the diabetes subgroup is another. And there is no incremental bleeding risk in this group over the whole population, so they get a much greater benefit without a greater risk. I hope this helps get rivaroxaban at the new lower dose used much more often.”
A total of 18,278 patients were randomly assigned to the combination of rivaroxaban and aspirin or aspirin alone in the COMPASS trial. Of these, 6922 had diabetes mellitus at baseline and 11,356 did not have diabetes.
Results from the current analysis show a consistent and similar relative risk reduction for benefit of rivaroxaban plus aspirin vs placebo plus aspirin in patients both with and without diabetes for the primary efficacy endpoint, a composite of cardiovascular death, myocardial infarction (MI), or stroke, with a hazard ratio of 0.74 for patients with diabetes and 0.77 for those without diabetes, the researchers report.
Because of the higher baseline risk in the diabetes subgroup, these patients had numerically larger absolute risk reductions with rivaroxaban than those without diabetes for the primary efficacy endpoint at 3 years (2.3% vs 1.4%) and for all-cause mortality (1.9% vs 0.6%).
These results translate into a number needed to treat (NNT) with rivaroxaban for 3 years to prevent one CV death, MI, or stroke of 44 for the diabetes group vs 73 for the nondiabetes group; the NNT to prevent one all-cause death was 54 for the diabetes group vs 167 for the nondiabetes group, the authors write.
Because the bleeding hazards were similar among patients with and without diabetes, the absolute net clinical benefit (MI, stroke, cardiovascular death, or bleeding leading to death or symptomatic bleeding into a critical organ) for rivaroxaban was “particularly favorable” in the diabetes group (2.7% fewer events in the diabetes group vs 1.0% fewer events in the nondiabetes group), they add.
Panelist at the ACC Featured Clinical Research session at which these results were presented, Jennifer Robinson, MD, University of Iowa College of Public Health, Iowa City, asked Bhatt how clinicians were supposed to decide which of the many new agents now becoming available for patients with stable coronary artery disease to prescribe first.
“We often forget about rivaroxaban when we’re thinking about what to add next for our secondary prevention patients,” she said. “You also led the REDUCE-IT trial showing benefit of icosapent ethyl, icosapent ethyl icosapent ethyl icosapent ethyl and there is also ezetimibe, PCSK9 inhibitors and SGLT2 inhibitors. For your patients with coronary disease who are already on a high dose statin which one of these would you add next?”
“That is what physicians need to ponder all the time,” Bhatt replied. “And when a patient has several risk factors that are not well controlled, I guess it’s all important. I go through a checklist with my patients and try and figure what they’re not on that could further reduce their risk.”
“In the COMPASS trial there was an overall positive result with rivaroxaban in the whole population. And now we have shown that patients with diabetes had an even greater absolute risk reduction. That pattern has also been seen with other classes of agents including the statins, PCSK9 inhibitors, and icosapent ethyl,” Bhatt noted.
“In patients with diabetes, I will usually target whatever is standing out most at that time. If their glycemic control is completely out of whack, then that is what I would focus on first, and these days often with a SGLT2 inhibitor or GLP-1 agonist. If the LDL was out of control, I would add ezetimibe or a PCSK9 inhibitor. If the triglycerides were high, I would add icosapent ethyl. If multiple things were out of control, I would usually focus on the number most out of kilter first and try not to forget about everything else.”
But Bhatt noted that the challenge with rivaroxaban is that there is no test of thrombosis risk that would prompt the physician to take action. “Basically, the doctor just has to remember to do it. In that regard I would consider whether patients are at low bleeding risk and are they still at high ischemic risk despite controlling other risk factors and, if so, then I would add this low dose of rivaroxaban.”
Another panel member, Sekar Kathiresan, MD, asked Bhatt whether he recommended using available scores to assess the bleeding/thrombosis risk/benefits of adding an antithrombotic.
Bhatt replied: “That’s a terrific question. I guess the right answer is that we should be doing that, but in reality I have to concede that I don’t use these scores. They have shown appropriate C statistics in populations, but they are not fantastic in individual patients.”
“I have to confess that I use the eyeball test. There is nothing as good at predicting future bleeding as past bleeding. So if a patient has had bleeding problems on aspirin alone I wouldn’t add rivaroxaban. But if a patient hasn’t bled before, especially if they had some experience of dual antiplatelet therapy, then they would be good candidates for a low vascular dose of rivaroxaban,” he said.
“It is not as easy as with other drugs as there is always a bleeding trade-off with an antithrombotic. There is no such thing as a free lunch. So patients need careful assessment when considering prescribing rivaroxaban and regular reassessment over time to check if they have had any bleeding,” he added.
The COMPASS study was funded by Bayer. Bhatt reports honoraria from Bayer via the Population Health Research Institute for his role on the COMPASS trial and other research funding from Bayer to the Brigham & Women’s Hospital.
American College of Cardiology 2020 Scientific Session (ACC.20)/World Congress of Cardiology (WCC). Abstract 20-LB-20544-ACC. Presented March 28, 2020.
Circulation. Published online March 28, 2020. Full text.
This article first appeared on Medscape.com.
In the COMPASS trial of patients with stable coronary or peripheral artery disease (PAD), the combination of aspirin plus rivaroxaban, 2.5 mg twice daily, provided a larger absolute benefit on cardiovascular endpoints — including a threefold greater reduction in all-cause mortality — in patients with diabetes compared with the overall population.
The results of the diabetes subset of the COMPASS trial were presented by Deepak Bhatt, MD, Brigham and Women’s Hospital Heart & Vascular Center, Boston, Massachusetts, on March 28 at the “virtual” American College of Cardiology 2020 Scientific Session (ACC.20)/World Congress of Cardiology (WCC). They were also simultaneously published online in Circulation.
“Use of dual pathway inhibition with low-dose rivaroxaban plus aspirin is particularly attractive in high-risk patients such as those with diabetes,” Bhatt concluded.
The COMPASS trial was first reported in 2017 and showed a new low dose of rivaroxaban (2.5-mg twice-daily; Xarelto, Bayer/Janssen Pharmaceuticals) plus aspirin, 100 mg once daily, was associated with a reduction in ischemic events and mortality and a superior net clinical benefit, balancing ischemic benefit with severe bleeding, compared with aspirin alone for secondary prevention in patients with stable atherosclerotic vascular disease.
But clinicians have been slow to prescribe rivaroxaban in this new and very large population.
“It’s been more than 2 years now since main COMPASS results, and there isn’t a sense that this therapy has really caught on,” chair of the current ACC session at which the diabetes subgroup results were presented, Hadley Wilson, MD, Sanger Heart and Vascular Institute, Charlotte, North Carolina, commented:
He asked Bhatt whether the diabetes subgroup may be “the tipping point that will make people aware of rivaroxaban and then that may trickle down to other patients.”
Bhatt said that he hoped that would be the case. “We as a steering committee of this trial could say the results were positive so rivaroxaban should now be used in everyone with stable coronary or peripheral arterial disease, but that is impractical and as you out point out it hasn’t happened,” he replied.
“In PAD/vascular medicine we have embraced this new therapy. In the broader cardiology world there are a lot of patients with stable coronary arterial disease at high ischemic risk who could take rivaroxaban, but its use is bound to be limited by it being a branded drug and the fact that there is a bleeding risk,” Bhatt explained.
“I think we need to identify patients with the highest ischemic risk and focus drugs such as these with a financial cost and a bleeding risk on those who most likely will derive the greatest absolute reduction in risk,” he said. “The PAD subgroup is one group where this is the case, and now we have shown the diabetes subgroup is another. And there is no incremental bleeding risk in this group over the whole population, so they get a much greater benefit without a greater risk. I hope this helps get rivaroxaban at the new lower dose used much more often.”
A total of 18,278 patients were randomly assigned to the combination of rivaroxaban and aspirin or aspirin alone in the COMPASS trial. Of these, 6922 had diabetes mellitus at baseline and 11,356 did not have diabetes.
Results from the current analysis show a consistent and similar relative risk reduction for benefit of rivaroxaban plus aspirin vs placebo plus aspirin in patients both with and without diabetes for the primary efficacy endpoint, a composite of cardiovascular death, myocardial infarction (MI), or stroke, with a hazard ratio of 0.74 for patients with diabetes and 0.77 for those without diabetes, the researchers report.
Because of the higher baseline risk in the diabetes subgroup, these patients had numerically larger absolute risk reductions with rivaroxaban than those without diabetes for the primary efficacy endpoint at 3 years (2.3% vs 1.4%) and for all-cause mortality (1.9% vs 0.6%).
These results translate into a number needed to treat (NNT) with rivaroxaban for 3 years to prevent one CV death, MI, or stroke of 44 for the diabetes group vs 73 for the nondiabetes group; the NNT to prevent one all-cause death was 54 for the diabetes group vs 167 for the nondiabetes group, the authors write.
Because the bleeding hazards were similar among patients with and without diabetes, the absolute net clinical benefit (MI, stroke, cardiovascular death, or bleeding leading to death or symptomatic bleeding into a critical organ) for rivaroxaban was “particularly favorable” in the diabetes group (2.7% fewer events in the diabetes group vs 1.0% fewer events in the nondiabetes group), they add.
Panelist at the ACC Featured Clinical Research session at which these results were presented, Jennifer Robinson, MD, University of Iowa College of Public Health, Iowa City, asked Bhatt how clinicians were supposed to decide which of the many new agents now becoming available for patients with stable coronary artery disease to prescribe first.
“We often forget about rivaroxaban when we’re thinking about what to add next for our secondary prevention patients,” she said. “You also led the REDUCE-IT trial showing benefit of icosapent ethyl, icosapent ethyl icosapent ethyl icosapent ethyl and there is also ezetimibe, PCSK9 inhibitors and SGLT2 inhibitors. For your patients with coronary disease who are already on a high dose statin which one of these would you add next?”
“That is what physicians need to ponder all the time,” Bhatt replied. “And when a patient has several risk factors that are not well controlled, I guess it’s all important. I go through a checklist with my patients and try and figure what they’re not on that could further reduce their risk.”
“In the COMPASS trial there was an overall positive result with rivaroxaban in the whole population. And now we have shown that patients with diabetes had an even greater absolute risk reduction. That pattern has also been seen with other classes of agents including the statins, PCSK9 inhibitors, and icosapent ethyl,” Bhatt noted.
“In patients with diabetes, I will usually target whatever is standing out most at that time. If their glycemic control is completely out of whack, then that is what I would focus on first, and these days often with a SGLT2 inhibitor or GLP-1 agonist. If the LDL was out of control, I would add ezetimibe or a PCSK9 inhibitor. If the triglycerides were high, I would add icosapent ethyl. If multiple things were out of control, I would usually focus on the number most out of kilter first and try not to forget about everything else.”
But Bhatt noted that the challenge with rivaroxaban is that there is no test of thrombosis risk that would prompt the physician to take action. “Basically, the doctor just has to remember to do it. In that regard I would consider whether patients are at low bleeding risk and are they still at high ischemic risk despite controlling other risk factors and, if so, then I would add this low dose of rivaroxaban.”
Another panel member, Sekar Kathiresan, MD, asked Bhatt whether he recommended using available scores to assess the bleeding/thrombosis risk/benefits of adding an antithrombotic.
Bhatt replied: “That’s a terrific question. I guess the right answer is that we should be doing that, but in reality I have to concede that I don’t use these scores. They have shown appropriate C statistics in populations, but they are not fantastic in individual patients.”
“I have to confess that I use the eyeball test. There is nothing as good at predicting future bleeding as past bleeding. So if a patient has had bleeding problems on aspirin alone I wouldn’t add rivaroxaban. But if a patient hasn’t bled before, especially if they had some experience of dual antiplatelet therapy, then they would be good candidates for a low vascular dose of rivaroxaban,” he said.
“It is not as easy as with other drugs as there is always a bleeding trade-off with an antithrombotic. There is no such thing as a free lunch. So patients need careful assessment when considering prescribing rivaroxaban and regular reassessment over time to check if they have had any bleeding,” he added.
The COMPASS study was funded by Bayer. Bhatt reports honoraria from Bayer via the Population Health Research Institute for his role on the COMPASS trial and other research funding from Bayer to the Brigham & Women’s Hospital.
American College of Cardiology 2020 Scientific Session (ACC.20)/World Congress of Cardiology (WCC). Abstract 20-LB-20544-ACC. Presented March 28, 2020.
Circulation. Published online March 28, 2020. Full text.
This article first appeared on Medscape.com.
TAILOR-PCI: Clopidogrel genotyping trial narrowly misses endpoint
The largest trial to date investigating the clinical utility of using genetic testing to detect clopidogrel loss-of-function genotype to guide antiplatelet therapy in patients undergoing percutaneous coronary intervention (PCI) missed its primary endpoint of a 50% reduction in cardiovascular events at 1 year.
However, the TAILOR-PCI trial did show a 34% reduction in such events at 1 year, as well as a statistically significant 40% reduction in the total number of events per patient receiving genetically guided treatment compared with patients who received standard treatment.
In addition, a post hoc analysis found a significant 79% reduction in the rate of adverse events in the first 3 months of treatment among patients who received genetically guided therapy compared with those who did not.
The study was presented March 28 during the “virtual” American College of Cardiology 2020 Scientific Session (ACC.20)/World Congress of Cardiology.
“Although these results fell short of the effect size that we predicted, they nevertheless provide a signal that offers support for the benefit of genetically guided therapy, with approximately one-third fewer adverse events in the patients who received genetically guided treatment compared with those who did not,” concluded Naveen L. Pereira, MD, professor of medicine at the Mayo Clinic in Rochester, Minnesota, and co-principal investigator of the study.
Pereira said the post hoc analysis of the first 3 months of treatment was particularly interesting. “This period immediately after PCI is when patients are at the highest risk for adverse events. We now know that antiplatelet drug therapy is critical during the first 3 months after PCI. Our findings suggest that the lion’s share of the benefit of genetically guided therapy may occur during this high-risk period,” he noted.
However, he added, “Because this wasn’t a preplanned analysis, we can’t draw firm conclusions from it, but it merits further study.”
Asked during an ACC virtual press conference how these results may influence clinical practice, Pereira said he hopes it changes practice toward genotyping.
“We set a very high standard in trying to achieve a 50% reduction in events, but we did see a 34% reduction. I think the probability of the results being true is very high,” he said. “I hope people pay attention to that. I’m not sure what the guidelines will do, but I believe if clopidogrel genetic information is made available to the physician, not changing therapy in a patient who has the loss-of-function gene will now be very difficult.”
Discussant of the trial, Roxana Mehran, MD, Mount Sinai Hospital, New York City, said she thought the results were good enough clinically to justify using genotyping to guide therapy.
“The trial showed an absolute 1.8% reduction and a relative 34% reduction in cardiovascular events, which did not quite meet the P value for significance, and they are supported by a significant reduction in multiple events, and a large difference at 3 months, although these are not primary analyses. So, for me this trial has shown that tailoring antiplatelet therapy by genetic testing is beneficial,” she said.
Another outside commentator, Patrick O’Gara, MD, Brigham and Women’s Hospital, Boston, Massachusetts, described TAILOR-PCI as a “terrific study.”
“Together with the study presented last year showing genotype-guided clopidogrel treatment was noninferior to ticagrelor/prasugrel in STEMI [non-ST-segment elevation myocardial infarction] patients, it chips away at the biologic appropriateness of targeting therapies based on genetic risk,” he said.
“I would hate people to focus on the fact the primary endpoint was missed by one hundredth of a percentage point but hope they would rather consider the bigger picture of making this genotype test more available and accessible to inform clinical decision making,” O’Gara added. “It just makes too much sense to ignore this potential.”
The TAILOR-PCI trial enrolled 5302 patients from 40 centers in the United States, Canada, Mexico, and South Korea who had undergone PCI with stenting. They were randomly assigned to genetic testing for the clopidogrel loss-of-function variant or a group that received standard treatment (clopidogrel) without genetic testing.
In the genetic testing group, 35% of patients were found to have the clopidogrel loss-of-function variant and were therefore prescribed ticagrelor, whereas those without the loss-of-function variant received clopidogrel.
After 1 year, the primary endpoint, a composite of cardiovascular death, MI, stroke, definite or probable stent thrombosis, and severe recurrent ischemia, occurred in 35 patients (4%) of the group that received genetically guided treatment, compared with 54 (5.9%) in the conventionally treated group (adjusted hazard ratio [HR], 0.66; 95% confidence interval [CI], 0.43 - 1.02; P = .56).
A prespecified analysis of total events (rather than just analysis of first event per patient) showed a 40% reduction in the genotyped group (HR, 0.60; 95% CI, 0.41 - 0.89; P = .011).
“Multiple adverse events represent a higher burden on the patient, so it is encouraging to see a significant reduction in cumulative events with genetically guided therapy,” Pereira said.
There was no difference in the safety endpoint of TIMI major bleeding or minor bleeding between the two groups: 1.9% in the genetically guided group vs 1.6% in the conventional treatment group.
The results did not differ between various subgroups in the trial, including race or ethnicity. Although Asian patients have a higher occurrence of the clopidogrel loss-of-function gene, the event risk reductions were similar in Asian and white patients in the study.
Pereira said the study may have been underpowered because of recent improvements in care. When the TAILOR-PCI trial was designed in 2012, around 10% to 12% of patients who received a stent could be expected to have a major adverse event, but during the trial, greater use of drug-coated stents and other treatments significantly reduced the expected rate of adverse events and made it more difficult for the trial to reach its goal of a 50% reduction in adverse events with the number of patients enrolled, he explained.
As part of the discussion, Mehran pointed out that more than 80% of the patients in the trial had acute coronary syndrome (ACS) and yet were being sent home on clopidogrel, which she said she found “daunting.”
“This begs the question of whether they were lower-risk patients and not really the hot unstable ACS patients with large thrombus burden where we see higher event rates,” Mehran commented. She also noted the results must be considered in the new era of platelet monotherapy, where aspirin is being withdrawn, and asked whether clopidogrel monotherapy would be considered safe without aspirin on board.
The researchers are planning a cost-effectiveness analysis of genetically guided therapy based on these data, and they are also continuing to follow patients over the longer term.
The TAILOR-PCI study was funded by the Mayo Clinic in collaboration with the National Heart, Lung, and Blood Institute. Spartan Bioscience Inc supplied the genetic tests used. Pereira reports no relevant disclosures.
American College of Cardiology 2020 Scientific Session (ACC.20)/World Congress of Cardiology. Abstract 20-LB-20309-ACC. Presented March 28, 2020.
This article first appeared on Medscape.com.
The largest trial to date investigating the clinical utility of using genetic testing to detect clopidogrel loss-of-function genotype to guide antiplatelet therapy in patients undergoing percutaneous coronary intervention (PCI) missed its primary endpoint of a 50% reduction in cardiovascular events at 1 year.
However, the TAILOR-PCI trial did show a 34% reduction in such events at 1 year, as well as a statistically significant 40% reduction in the total number of events per patient receiving genetically guided treatment compared with patients who received standard treatment.
In addition, a post hoc analysis found a significant 79% reduction in the rate of adverse events in the first 3 months of treatment among patients who received genetically guided therapy compared with those who did not.
The study was presented March 28 during the “virtual” American College of Cardiology 2020 Scientific Session (ACC.20)/World Congress of Cardiology.
“Although these results fell short of the effect size that we predicted, they nevertheless provide a signal that offers support for the benefit of genetically guided therapy, with approximately one-third fewer adverse events in the patients who received genetically guided treatment compared with those who did not,” concluded Naveen L. Pereira, MD, professor of medicine at the Mayo Clinic in Rochester, Minnesota, and co-principal investigator of the study.
Pereira said the post hoc analysis of the first 3 months of treatment was particularly interesting. “This period immediately after PCI is when patients are at the highest risk for adverse events. We now know that antiplatelet drug therapy is critical during the first 3 months after PCI. Our findings suggest that the lion’s share of the benefit of genetically guided therapy may occur during this high-risk period,” he noted.
However, he added, “Because this wasn’t a preplanned analysis, we can’t draw firm conclusions from it, but it merits further study.”
Asked during an ACC virtual press conference how these results may influence clinical practice, Pereira said he hopes it changes practice toward genotyping.
“We set a very high standard in trying to achieve a 50% reduction in events, but we did see a 34% reduction. I think the probability of the results being true is very high,” he said. “I hope people pay attention to that. I’m not sure what the guidelines will do, but I believe if clopidogrel genetic information is made available to the physician, not changing therapy in a patient who has the loss-of-function gene will now be very difficult.”
Discussant of the trial, Roxana Mehran, MD, Mount Sinai Hospital, New York City, said she thought the results were good enough clinically to justify using genotyping to guide therapy.
“The trial showed an absolute 1.8% reduction and a relative 34% reduction in cardiovascular events, which did not quite meet the P value for significance, and they are supported by a significant reduction in multiple events, and a large difference at 3 months, although these are not primary analyses. So, for me this trial has shown that tailoring antiplatelet therapy by genetic testing is beneficial,” she said.
Another outside commentator, Patrick O’Gara, MD, Brigham and Women’s Hospital, Boston, Massachusetts, described TAILOR-PCI as a “terrific study.”
“Together with the study presented last year showing genotype-guided clopidogrel treatment was noninferior to ticagrelor/prasugrel in STEMI [non-ST-segment elevation myocardial infarction] patients, it chips away at the biologic appropriateness of targeting therapies based on genetic risk,” he said.
“I would hate people to focus on the fact the primary endpoint was missed by one hundredth of a percentage point but hope they would rather consider the bigger picture of making this genotype test more available and accessible to inform clinical decision making,” O’Gara added. “It just makes too much sense to ignore this potential.”
The TAILOR-PCI trial enrolled 5302 patients from 40 centers in the United States, Canada, Mexico, and South Korea who had undergone PCI with stenting. They were randomly assigned to genetic testing for the clopidogrel loss-of-function variant or a group that received standard treatment (clopidogrel) without genetic testing.
In the genetic testing group, 35% of patients were found to have the clopidogrel loss-of-function variant and were therefore prescribed ticagrelor, whereas those without the loss-of-function variant received clopidogrel.
After 1 year, the primary endpoint, a composite of cardiovascular death, MI, stroke, definite or probable stent thrombosis, and severe recurrent ischemia, occurred in 35 patients (4%) of the group that received genetically guided treatment, compared with 54 (5.9%) in the conventionally treated group (adjusted hazard ratio [HR], 0.66; 95% confidence interval [CI], 0.43 - 1.02; P = .56).
A prespecified analysis of total events (rather than just analysis of first event per patient) showed a 40% reduction in the genotyped group (HR, 0.60; 95% CI, 0.41 - 0.89; P = .011).
“Multiple adverse events represent a higher burden on the patient, so it is encouraging to see a significant reduction in cumulative events with genetically guided therapy,” Pereira said.
There was no difference in the safety endpoint of TIMI major bleeding or minor bleeding between the two groups: 1.9% in the genetically guided group vs 1.6% in the conventional treatment group.
The results did not differ between various subgroups in the trial, including race or ethnicity. Although Asian patients have a higher occurrence of the clopidogrel loss-of-function gene, the event risk reductions were similar in Asian and white patients in the study.
Pereira said the study may have been underpowered because of recent improvements in care. When the TAILOR-PCI trial was designed in 2012, around 10% to 12% of patients who received a stent could be expected to have a major adverse event, but during the trial, greater use of drug-coated stents and other treatments significantly reduced the expected rate of adverse events and made it more difficult for the trial to reach its goal of a 50% reduction in adverse events with the number of patients enrolled, he explained.
As part of the discussion, Mehran pointed out that more than 80% of the patients in the trial had acute coronary syndrome (ACS) and yet were being sent home on clopidogrel, which she said she found “daunting.”
“This begs the question of whether they were lower-risk patients and not really the hot unstable ACS patients with large thrombus burden where we see higher event rates,” Mehran commented. She also noted the results must be considered in the new era of platelet monotherapy, where aspirin is being withdrawn, and asked whether clopidogrel monotherapy would be considered safe without aspirin on board.
The researchers are planning a cost-effectiveness analysis of genetically guided therapy based on these data, and they are also continuing to follow patients over the longer term.
The TAILOR-PCI study was funded by the Mayo Clinic in collaboration with the National Heart, Lung, and Blood Institute. Spartan Bioscience Inc supplied the genetic tests used. Pereira reports no relevant disclosures.
American College of Cardiology 2020 Scientific Session (ACC.20)/World Congress of Cardiology. Abstract 20-LB-20309-ACC. Presented March 28, 2020.
This article first appeared on Medscape.com.
The largest trial to date investigating the clinical utility of using genetic testing to detect clopidogrel loss-of-function genotype to guide antiplatelet therapy in patients undergoing percutaneous coronary intervention (PCI) missed its primary endpoint of a 50% reduction in cardiovascular events at 1 year.
However, the TAILOR-PCI trial did show a 34% reduction in such events at 1 year, as well as a statistically significant 40% reduction in the total number of events per patient receiving genetically guided treatment compared with patients who received standard treatment.
In addition, a post hoc analysis found a significant 79% reduction in the rate of adverse events in the first 3 months of treatment among patients who received genetically guided therapy compared with those who did not.
The study was presented March 28 during the “virtual” American College of Cardiology 2020 Scientific Session (ACC.20)/World Congress of Cardiology.
“Although these results fell short of the effect size that we predicted, they nevertheless provide a signal that offers support for the benefit of genetically guided therapy, with approximately one-third fewer adverse events in the patients who received genetically guided treatment compared with those who did not,” concluded Naveen L. Pereira, MD, professor of medicine at the Mayo Clinic in Rochester, Minnesota, and co-principal investigator of the study.
Pereira said the post hoc analysis of the first 3 months of treatment was particularly interesting. “This period immediately after PCI is when patients are at the highest risk for adverse events. We now know that antiplatelet drug therapy is critical during the first 3 months after PCI. Our findings suggest that the lion’s share of the benefit of genetically guided therapy may occur during this high-risk period,” he noted.
However, he added, “Because this wasn’t a preplanned analysis, we can’t draw firm conclusions from it, but it merits further study.”
Asked during an ACC virtual press conference how these results may influence clinical practice, Pereira said he hopes it changes practice toward genotyping.
“We set a very high standard in trying to achieve a 50% reduction in events, but we did see a 34% reduction. I think the probability of the results being true is very high,” he said. “I hope people pay attention to that. I’m not sure what the guidelines will do, but I believe if clopidogrel genetic information is made available to the physician, not changing therapy in a patient who has the loss-of-function gene will now be very difficult.”
Discussant of the trial, Roxana Mehran, MD, Mount Sinai Hospital, New York City, said she thought the results were good enough clinically to justify using genotyping to guide therapy.
“The trial showed an absolute 1.8% reduction and a relative 34% reduction in cardiovascular events, which did not quite meet the P value for significance, and they are supported by a significant reduction in multiple events, and a large difference at 3 months, although these are not primary analyses. So, for me this trial has shown that tailoring antiplatelet therapy by genetic testing is beneficial,” she said.
Another outside commentator, Patrick O’Gara, MD, Brigham and Women’s Hospital, Boston, Massachusetts, described TAILOR-PCI as a “terrific study.”
“Together with the study presented last year showing genotype-guided clopidogrel treatment was noninferior to ticagrelor/prasugrel in STEMI [non-ST-segment elevation myocardial infarction] patients, it chips away at the biologic appropriateness of targeting therapies based on genetic risk,” he said.
“I would hate people to focus on the fact the primary endpoint was missed by one hundredth of a percentage point but hope they would rather consider the bigger picture of making this genotype test more available and accessible to inform clinical decision making,” O’Gara added. “It just makes too much sense to ignore this potential.”
The TAILOR-PCI trial enrolled 5302 patients from 40 centers in the United States, Canada, Mexico, and South Korea who had undergone PCI with stenting. They were randomly assigned to genetic testing for the clopidogrel loss-of-function variant or a group that received standard treatment (clopidogrel) without genetic testing.
In the genetic testing group, 35% of patients were found to have the clopidogrel loss-of-function variant and were therefore prescribed ticagrelor, whereas those without the loss-of-function variant received clopidogrel.
After 1 year, the primary endpoint, a composite of cardiovascular death, MI, stroke, definite or probable stent thrombosis, and severe recurrent ischemia, occurred in 35 patients (4%) of the group that received genetically guided treatment, compared with 54 (5.9%) in the conventionally treated group (adjusted hazard ratio [HR], 0.66; 95% confidence interval [CI], 0.43 - 1.02; P = .56).
A prespecified analysis of total events (rather than just analysis of first event per patient) showed a 40% reduction in the genotyped group (HR, 0.60; 95% CI, 0.41 - 0.89; P = .011).
“Multiple adverse events represent a higher burden on the patient, so it is encouraging to see a significant reduction in cumulative events with genetically guided therapy,” Pereira said.
There was no difference in the safety endpoint of TIMI major bleeding or minor bleeding between the two groups: 1.9% in the genetically guided group vs 1.6% in the conventional treatment group.
The results did not differ between various subgroups in the trial, including race or ethnicity. Although Asian patients have a higher occurrence of the clopidogrel loss-of-function gene, the event risk reductions were similar in Asian and white patients in the study.
Pereira said the study may have been underpowered because of recent improvements in care. When the TAILOR-PCI trial was designed in 2012, around 10% to 12% of patients who received a stent could be expected to have a major adverse event, but during the trial, greater use of drug-coated stents and other treatments significantly reduced the expected rate of adverse events and made it more difficult for the trial to reach its goal of a 50% reduction in adverse events with the number of patients enrolled, he explained.
As part of the discussion, Mehran pointed out that more than 80% of the patients in the trial had acute coronary syndrome (ACS) and yet were being sent home on clopidogrel, which she said she found “daunting.”
“This begs the question of whether they were lower-risk patients and not really the hot unstable ACS patients with large thrombus burden where we see higher event rates,” Mehran commented. She also noted the results must be considered in the new era of platelet monotherapy, where aspirin is being withdrawn, and asked whether clopidogrel monotherapy would be considered safe without aspirin on board.
The researchers are planning a cost-effectiveness analysis of genetically guided therapy based on these data, and they are also continuing to follow patients over the longer term.
The TAILOR-PCI study was funded by the Mayo Clinic in collaboration with the National Heart, Lung, and Blood Institute. Spartan Bioscience Inc supplied the genetic tests used. Pereira reports no relevant disclosures.
American College of Cardiology 2020 Scientific Session (ACC.20)/World Congress of Cardiology. Abstract 20-LB-20309-ACC. Presented March 28, 2020.
This article first appeared on Medscape.com.
Primordial cardiovascular prevention draws closer
A powerful genetic predisposition to cardiovascular disease was overcome by low lifetime exposure to LDL cholesterol and systolic blood pressure in a naturalistic study conducted in nearly half a million people, Brian A. Ference, MD, reported at the joint scientific sessions of the American College of Cardiology and the World Heart Federation. The meeting was conducted online after its cancellation because of the COVID-19 pandemic.
This novel finding potentially opens the door to primordial cardiovascular prevention, the earliest possible form of primary prevention, in which cardiovascular risk factors are curtailed before they can become established.
“It’s important to note that the trajectories of lifetime risk for cardiovascular disease predicted by a PGS [polygenic risk score] are not fixed. At the same level of a PGS for coronary artery disease, participants with lower lifetime exposure to LDL and systolic blood pressure had a lower trajectory of risk for cardiovascular disease. This finding implies that the trajectory of cardiovascular risk predicted by a PGS can be reduced by lowering LDL and blood pressure,” observed Dr. Ference, professor of translational therapeutics and executive director of the Center for Naturally Randomised Trials at the University of Cambridge (England).
Together with an international team of coinvestigators, he analyzed lifetime cardiovascular risk as predicted by a PGS derived by genomic testing in relation to lifetime LDL and systolic blood pressure levels in 445,566 participants in the UK Biobank. Subjects had a mean age of 57.2 years at enrollment and 65.2 years at last follow-up. The primary study outcome, a first major coronary event (MCE) as defined by a fatal or nonfatal MI or coronary revascularization, occurred in 23,032 subjects.
The investigators found a stepwise increase in MCE risk across increasing quintiles of genetic risk as reflected in the PGS, such that participants in the top PGS quintile were at 2.8-fold greater risk of an MCE than those in the first quintile. The risk was essentially the same in men and women.
A key finding was that, at any level of lifetime MCE risk as defined by PGS, the actual event rate varied 10-fold depending upon lifetime exposure to LDL cholesterol and systolic blood pressure (SBP). For example, men in the top PGS quintile with high lifetime SBP and LDL cholesterol had a 93% lifetime MCE risk, but that MCE risk plummeted to 8% in those in the top quintile but with low lifetime SBP and LDL cholesterol.
Small differences in those two cardiovascular risk factors over the course of many decades had a big impact. For example, it took only a 10-mg/dL lower lifetime exposure to LDL cholesterol and a 2–mm Hg lower SBP to blunt the trajectory of lifetime risk for MCE in individuals in the middle quintile of PGS to the more favorable trajectory of those in the lowest PGS quintile. Conversely, with a 10-mg/dL increase in LDL cholesterol and 2–mm Hg greater SBP over the course of a lifetime, the trajectory of risk for people in the middle quintile of PGS became essentially superimposable upon the trajectory associated with the highest PGS quintile, the cardiologist explained.
“Participants with low lifetime exposure to LDL and blood pressure had a low lifetime risk of cardiovascular disease at all levels of PGS for coronary disease. This implies that LDL and blood pressure, which are modifiable, may be more powerful determinants of lifetime risk than polygenic predisposition,” Dr. Ference declared.
Discussant Vera Bittner, MD, professor of medicine at the University of Alabama, Birmingham, said that for her this study carried a heartening take-home message: “The polygenic risk score can stratify the population into different risk groups and, at the same time, lifetime exposure to LDL and blood pressure significantly modifies the risk, suggesting that genetics is not destiny, and we may be able to intervene.”
“To be able to know what your cardiovascular risk is from an early age and to plan therapies to prevent cardiovascular disease would be incredible,” agreed session chair B. Hadley Wilson, MD, of the Sanger Heart and Vascular Institute in Charlotte, N.C.
Sekar Kathiresan, MD, said the study introduces the PGS as a new risk factor for coronary artery disease. Focusing efforts to achieve lifelong low exposure to LDL cholesterol and blood pressure in those individuals in the top 10%-20% in PGS should provide a great absolute reduction in MCE risk.
“It potentially can give you a 30- or 40-year head start in understanding who’s at risk because the factor can be measured as early as birth,” observed Dr. Kathiresan, a cardiologist who is director of the Center for Genomic Medicine at Massachusetts General Hospital, Boston.
“It’s also very inexpensive: You get the information once, bank it, and use it throughout life,” noted Paul M. Ridker, MD, director of the Center for Cardiovascular Disease Prevention and professor of medicine at Harvard Medical School, Boston.
“A genome-wide scan will give us information not just on cardiovascular risk, but on cancer risk, on risk of kidney disease, and on the risk of a host of other issues. It’s a very different way of thinking about risk presentation across a whole variety of endpoints,” Dr. Ridker added.
Dr. Ference reported receiving fees and/or research grants from Merck, Amgen, Regeneron, Sanofi, Novartis, Pfizer, Eli Lilly, NovoNordisk, The Medicines Company, Mylan, Daiichi Sankyo, Silence Therapeutics, Ionis Pharmaceuticals, dalCOR, CiVi Pharma, KrKa Pharmaceuticals, Medtronic, and Celera.
A powerful genetic predisposition to cardiovascular disease was overcome by low lifetime exposure to LDL cholesterol and systolic blood pressure in a naturalistic study conducted in nearly half a million people, Brian A. Ference, MD, reported at the joint scientific sessions of the American College of Cardiology and the World Heart Federation. The meeting was conducted online after its cancellation because of the COVID-19 pandemic.
This novel finding potentially opens the door to primordial cardiovascular prevention, the earliest possible form of primary prevention, in which cardiovascular risk factors are curtailed before they can become established.
“It’s important to note that the trajectories of lifetime risk for cardiovascular disease predicted by a PGS [polygenic risk score] are not fixed. At the same level of a PGS for coronary artery disease, participants with lower lifetime exposure to LDL and systolic blood pressure had a lower trajectory of risk for cardiovascular disease. This finding implies that the trajectory of cardiovascular risk predicted by a PGS can be reduced by lowering LDL and blood pressure,” observed Dr. Ference, professor of translational therapeutics and executive director of the Center for Naturally Randomised Trials at the University of Cambridge (England).
Together with an international team of coinvestigators, he analyzed lifetime cardiovascular risk as predicted by a PGS derived by genomic testing in relation to lifetime LDL and systolic blood pressure levels in 445,566 participants in the UK Biobank. Subjects had a mean age of 57.2 years at enrollment and 65.2 years at last follow-up. The primary study outcome, a first major coronary event (MCE) as defined by a fatal or nonfatal MI or coronary revascularization, occurred in 23,032 subjects.
The investigators found a stepwise increase in MCE risk across increasing quintiles of genetic risk as reflected in the PGS, such that participants in the top PGS quintile were at 2.8-fold greater risk of an MCE than those in the first quintile. The risk was essentially the same in men and women.
A key finding was that, at any level of lifetime MCE risk as defined by PGS, the actual event rate varied 10-fold depending upon lifetime exposure to LDL cholesterol and systolic blood pressure (SBP). For example, men in the top PGS quintile with high lifetime SBP and LDL cholesterol had a 93% lifetime MCE risk, but that MCE risk plummeted to 8% in those in the top quintile but with low lifetime SBP and LDL cholesterol.
Small differences in those two cardiovascular risk factors over the course of many decades had a big impact. For example, it took only a 10-mg/dL lower lifetime exposure to LDL cholesterol and a 2–mm Hg lower SBP to blunt the trajectory of lifetime risk for MCE in individuals in the middle quintile of PGS to the more favorable trajectory of those in the lowest PGS quintile. Conversely, with a 10-mg/dL increase in LDL cholesterol and 2–mm Hg greater SBP over the course of a lifetime, the trajectory of risk for people in the middle quintile of PGS became essentially superimposable upon the trajectory associated with the highest PGS quintile, the cardiologist explained.
“Participants with low lifetime exposure to LDL and blood pressure had a low lifetime risk of cardiovascular disease at all levels of PGS for coronary disease. This implies that LDL and blood pressure, which are modifiable, may be more powerful determinants of lifetime risk than polygenic predisposition,” Dr. Ference declared.
Discussant Vera Bittner, MD, professor of medicine at the University of Alabama, Birmingham, said that for her this study carried a heartening take-home message: “The polygenic risk score can stratify the population into different risk groups and, at the same time, lifetime exposure to LDL and blood pressure significantly modifies the risk, suggesting that genetics is not destiny, and we may be able to intervene.”
“To be able to know what your cardiovascular risk is from an early age and to plan therapies to prevent cardiovascular disease would be incredible,” agreed session chair B. Hadley Wilson, MD, of the Sanger Heart and Vascular Institute in Charlotte, N.C.
Sekar Kathiresan, MD, said the study introduces the PGS as a new risk factor for coronary artery disease. Focusing efforts to achieve lifelong low exposure to LDL cholesterol and blood pressure in those individuals in the top 10%-20% in PGS should provide a great absolute reduction in MCE risk.
“It potentially can give you a 30- or 40-year head start in understanding who’s at risk because the factor can be measured as early as birth,” observed Dr. Kathiresan, a cardiologist who is director of the Center for Genomic Medicine at Massachusetts General Hospital, Boston.
“It’s also very inexpensive: You get the information once, bank it, and use it throughout life,” noted Paul M. Ridker, MD, director of the Center for Cardiovascular Disease Prevention and professor of medicine at Harvard Medical School, Boston.
“A genome-wide scan will give us information not just on cardiovascular risk, but on cancer risk, on risk of kidney disease, and on the risk of a host of other issues. It’s a very different way of thinking about risk presentation across a whole variety of endpoints,” Dr. Ridker added.
Dr. Ference reported receiving fees and/or research grants from Merck, Amgen, Regeneron, Sanofi, Novartis, Pfizer, Eli Lilly, NovoNordisk, The Medicines Company, Mylan, Daiichi Sankyo, Silence Therapeutics, Ionis Pharmaceuticals, dalCOR, CiVi Pharma, KrKa Pharmaceuticals, Medtronic, and Celera.
A powerful genetic predisposition to cardiovascular disease was overcome by low lifetime exposure to LDL cholesterol and systolic blood pressure in a naturalistic study conducted in nearly half a million people, Brian A. Ference, MD, reported at the joint scientific sessions of the American College of Cardiology and the World Heart Federation. The meeting was conducted online after its cancellation because of the COVID-19 pandemic.
This novel finding potentially opens the door to primordial cardiovascular prevention, the earliest possible form of primary prevention, in which cardiovascular risk factors are curtailed before they can become established.
“It’s important to note that the trajectories of lifetime risk for cardiovascular disease predicted by a PGS [polygenic risk score] are not fixed. At the same level of a PGS for coronary artery disease, participants with lower lifetime exposure to LDL and systolic blood pressure had a lower trajectory of risk for cardiovascular disease. This finding implies that the trajectory of cardiovascular risk predicted by a PGS can be reduced by lowering LDL and blood pressure,” observed Dr. Ference, professor of translational therapeutics and executive director of the Center for Naturally Randomised Trials at the University of Cambridge (England).
Together with an international team of coinvestigators, he analyzed lifetime cardiovascular risk as predicted by a PGS derived by genomic testing in relation to lifetime LDL and systolic blood pressure levels in 445,566 participants in the UK Biobank. Subjects had a mean age of 57.2 years at enrollment and 65.2 years at last follow-up. The primary study outcome, a first major coronary event (MCE) as defined by a fatal or nonfatal MI or coronary revascularization, occurred in 23,032 subjects.
The investigators found a stepwise increase in MCE risk across increasing quintiles of genetic risk as reflected in the PGS, such that participants in the top PGS quintile were at 2.8-fold greater risk of an MCE than those in the first quintile. The risk was essentially the same in men and women.
A key finding was that, at any level of lifetime MCE risk as defined by PGS, the actual event rate varied 10-fold depending upon lifetime exposure to LDL cholesterol and systolic blood pressure (SBP). For example, men in the top PGS quintile with high lifetime SBP and LDL cholesterol had a 93% lifetime MCE risk, but that MCE risk plummeted to 8% in those in the top quintile but with low lifetime SBP and LDL cholesterol.
Small differences in those two cardiovascular risk factors over the course of many decades had a big impact. For example, it took only a 10-mg/dL lower lifetime exposure to LDL cholesterol and a 2–mm Hg lower SBP to blunt the trajectory of lifetime risk for MCE in individuals in the middle quintile of PGS to the more favorable trajectory of those in the lowest PGS quintile. Conversely, with a 10-mg/dL increase in LDL cholesterol and 2–mm Hg greater SBP over the course of a lifetime, the trajectory of risk for people in the middle quintile of PGS became essentially superimposable upon the trajectory associated with the highest PGS quintile, the cardiologist explained.
“Participants with low lifetime exposure to LDL and blood pressure had a low lifetime risk of cardiovascular disease at all levels of PGS for coronary disease. This implies that LDL and blood pressure, which are modifiable, may be more powerful determinants of lifetime risk than polygenic predisposition,” Dr. Ference declared.
Discussant Vera Bittner, MD, professor of medicine at the University of Alabama, Birmingham, said that for her this study carried a heartening take-home message: “The polygenic risk score can stratify the population into different risk groups and, at the same time, lifetime exposure to LDL and blood pressure significantly modifies the risk, suggesting that genetics is not destiny, and we may be able to intervene.”
“To be able to know what your cardiovascular risk is from an early age and to plan therapies to prevent cardiovascular disease would be incredible,” agreed session chair B. Hadley Wilson, MD, of the Sanger Heart and Vascular Institute in Charlotte, N.C.
Sekar Kathiresan, MD, said the study introduces the PGS as a new risk factor for coronary artery disease. Focusing efforts to achieve lifelong low exposure to LDL cholesterol and blood pressure in those individuals in the top 10%-20% in PGS should provide a great absolute reduction in MCE risk.
“It potentially can give you a 30- or 40-year head start in understanding who’s at risk because the factor can be measured as early as birth,” observed Dr. Kathiresan, a cardiologist who is director of the Center for Genomic Medicine at Massachusetts General Hospital, Boston.
“It’s also very inexpensive: You get the information once, bank it, and use it throughout life,” noted Paul M. Ridker, MD, director of the Center for Cardiovascular Disease Prevention and professor of medicine at Harvard Medical School, Boston.
“A genome-wide scan will give us information not just on cardiovascular risk, but on cancer risk, on risk of kidney disease, and on the risk of a host of other issues. It’s a very different way of thinking about risk presentation across a whole variety of endpoints,” Dr. Ridker added.
Dr. Ference reported receiving fees and/or research grants from Merck, Amgen, Regeneron, Sanofi, Novartis, Pfizer, Eli Lilly, NovoNordisk, The Medicines Company, Mylan, Daiichi Sankyo, Silence Therapeutics, Ionis Pharmaceuticals, dalCOR, CiVi Pharma, KrKa Pharmaceuticals, Medtronic, and Celera.
REPORTING FROM ACC 20
Rivaroxaban plus aspirin safely benefits PAD patients after limb revascularization
A combined antithrombotic regimen of rivaroxaban plus aspirin was safe and effective for reducing ischemic events in patients with symptomatic peripheral artery disease who had just undergone peripheral artery revascularization in VOYAGER PAD, a multicenter randomized trial with nearly 6,600 patients.
The study and its results were a groundbreaking advance for this patient population, who until now have had no evidence-based treatment available, Mark P. Bonaca, MD, said on March 28 at the joint scientific sessions of the American College of Cardiology and the World Heart Federation. The meeting was conducted online after its cancellation because of the COVID-19 pandemic.
The study design excluded a small percentage of patients (about 2%) because of their very high bleeding-risk history. Among the treated patients, in those who received a combination of 2.5 mg rivaroxaban twice daily plus 100 mg of aspirin daily, bleeding events were more common, compared with control patients who received aspirin alone. But the patients who received both drugs showed no excess of fatal bleeds or intracranial hemorrhages, and the rate of ischemic events prevented by rivaroxaban plus aspirin exceeded the excess rate of bleeds by three- to sixfold, depending on how bleeding episodes were defined, noted Dr. Bonaca, executive director of CPC Clinical Research and CPC Community Health, an academic research organization affiliated with the University of Colorado at Denver in Aurora.
“This was a much anticipated and important trial. Those of us who treat patients with lower-limb peripheral artery disease have not had much evidence on how to treat these patients, particularly those who have just undergone revascularization. This trial gives us the evidence,” commented Mark A. Creager, MD, professor of medicine and director of the Heart and Vascular Center at Dartmouth-Hitchcock Medical Center in Lebanon, N.H. “The bleeding risk [from adding rivaroxaban treatment] was substantially less than the benefit from preventing major adverse limb events and major adverse cardiovascular events,” producing a “favorable balance” of benefit, compared with risk, Dr. Creager said in an interview. “In the right patients, the benefit greatly outweighed the risk.”
“This was an incredible trial that will advance care,” commented Joshua A. Beckman, MD, professor of medicine and director of Vascular Medicine at Vanderbilt University in Nashville, Tenn. “The treatment was beneficial for patients across a range of symptom severity, from claudication to critical limb ischemia,” and the results expand the range of patients proven to benefit from the rivaroxaban plus aspirin combination from the types of patients with peripheral artery disease (PAD) enrolled in the COMPASS trial. That pivotal trial showed similar benefit from the dual-antithrombotic regimen, but in patients who had both coronary artery disease as well as atherosclerotic disease in at least one additional vascular bed, such as lower-limb arteries (N Engl J Med. 2017 Oct 5;377[14]:1319-30). In addition to “bringing acute limb ischemia to the cardiovascular community,” the results also identified a very useful time point in the clinical presentation of these patients for starting a combined rivaroxaban plus aspirin regimen: when patients are hospitalized for their revascularization procedure, said Dr. Beckman, a designated discussant for the report.
Among the 6,564 patients randomized in the study, about two-thirds underwent endovascular revascularization within 10 days before starting their study treatment, and the remaining third had undergone surgical revascularization. The study focused on patients “with symptomatic PAD but without known coronary artery disease,” noted Dr. Bonaca.
VOYAGER PAD trial
The VOYAGER PAD (Vascular Outcomes Study of Acetylsalicylic Acid Along With Rivaroxaban in Endovascular Or Surgical Limb Revascularization for Peripheral Artery Disease) trial enrolled patients during 2015-2018 at 534 sites in 34 countries. The study’s primary endpoint was a composite of acute limb ischemia, major amputation for vascular causes, myocardial infarction, ischemic stroke, or death from cardiovascular causes, and was reduced during a median follow-up of 28 months from 19.9% with aspirin alone to 17.3% on the combined regimen, a 2.6% absolute difference and a 15% relative risk reduction that was statistically significant, an endpoint primarily driven by a reduction in acute limb ischemia. The primary safety endpoint was the rate of TIMI (Thrombolysis in Myocardial Infarction) major bleeds, which was 0.8% higher in the patients who received the anticoagulant, a 43% relative increase that just missed statistical significance. But that result demonstrated the small but important increased risk for bleeding events that the dual regimen produced in these patients, Dr. Bonaca said. Simultaneously with his report the findings also appeared in an article published online (N Engl J Med. 2020 Mar 28. doi: 10.1056/NEJMoa2000052).
Dr. Bonaca cautioned that one limitation of his report on the primary outcome of VOYAGER PAD is that the results of an important subgroup analysis won’t be known until a second report during the ACC online sessions on March 29, which will examine the impact that treatment with the antiplatelet drug clopidogrel had on both the efficacy and safety outcomes. Half of the enrolled patients received clopidogrel at the discretion of their treating physicians; addition or exclusion of concurrent clopidogrel treatment was outside of the study’s design. “Is efficacy the same with or without clopidogrel, and what is the bleeding cost,” especially in patients who receive three antithrombotic drugs? “It will be very important to understand,” Dr. Bonaca said.
“Until now, we had no idea of what was the best antithrombotic strategy for patients after a successful peripheral vascular intervention.” VOYAGER PAD was “an unprecedented vascular study that addressed an unmet patient need,” commented Roxana Mehran, MD, a designated discussant for the study and professor of medicine and director of Interventional Cardiovascular Research at Mount Sinai Medical Center in New York.
VOYAGER PAD was sponsored by Bayer and Janssen, the companies that market rivaroxaban (Xarelto). The institution that Dr. Bonaca directs has received research funding from Bayer and Janssen, and also from Amgen, Aralez, AstraZeneca, Merck, Novo Nordisk, Pfizer, and Sanofi. Dr. Creager had no disclosures. Dr. Beckman has served as a data safety monitor for Bayer and for Novartis, and has been a consultant to Amgen, AstraZeneca, JanOne and Sanofi. Dr. Mehran has received research funding from Bayer and has been a consultant to Janssen, and she has also received research funding or been a consultant to several other companies.
SOURCE: Bonaca MP et al. ACC 20, Abstract 402-10.
A combined antithrombotic regimen of rivaroxaban plus aspirin was safe and effective for reducing ischemic events in patients with symptomatic peripheral artery disease who had just undergone peripheral artery revascularization in VOYAGER PAD, a multicenter randomized trial with nearly 6,600 patients.
The study and its results were a groundbreaking advance for this patient population, who until now have had no evidence-based treatment available, Mark P. Bonaca, MD, said on March 28 at the joint scientific sessions of the American College of Cardiology and the World Heart Federation. The meeting was conducted online after its cancellation because of the COVID-19 pandemic.
The study design excluded a small percentage of patients (about 2%) because of their very high bleeding-risk history. Among the treated patients, in those who received a combination of 2.5 mg rivaroxaban twice daily plus 100 mg of aspirin daily, bleeding events were more common, compared with control patients who received aspirin alone. But the patients who received both drugs showed no excess of fatal bleeds or intracranial hemorrhages, and the rate of ischemic events prevented by rivaroxaban plus aspirin exceeded the excess rate of bleeds by three- to sixfold, depending on how bleeding episodes were defined, noted Dr. Bonaca, executive director of CPC Clinical Research and CPC Community Health, an academic research organization affiliated with the University of Colorado at Denver in Aurora.
“This was a much anticipated and important trial. Those of us who treat patients with lower-limb peripheral artery disease have not had much evidence on how to treat these patients, particularly those who have just undergone revascularization. This trial gives us the evidence,” commented Mark A. Creager, MD, professor of medicine and director of the Heart and Vascular Center at Dartmouth-Hitchcock Medical Center in Lebanon, N.H. “The bleeding risk [from adding rivaroxaban treatment] was substantially less than the benefit from preventing major adverse limb events and major adverse cardiovascular events,” producing a “favorable balance” of benefit, compared with risk, Dr. Creager said in an interview. “In the right patients, the benefit greatly outweighed the risk.”
“This was an incredible trial that will advance care,” commented Joshua A. Beckman, MD, professor of medicine and director of Vascular Medicine at Vanderbilt University in Nashville, Tenn. “The treatment was beneficial for patients across a range of symptom severity, from claudication to critical limb ischemia,” and the results expand the range of patients proven to benefit from the rivaroxaban plus aspirin combination from the types of patients with peripheral artery disease (PAD) enrolled in the COMPASS trial. That pivotal trial showed similar benefit from the dual-antithrombotic regimen, but in patients who had both coronary artery disease as well as atherosclerotic disease in at least one additional vascular bed, such as lower-limb arteries (N Engl J Med. 2017 Oct 5;377[14]:1319-30). In addition to “bringing acute limb ischemia to the cardiovascular community,” the results also identified a very useful time point in the clinical presentation of these patients for starting a combined rivaroxaban plus aspirin regimen: when patients are hospitalized for their revascularization procedure, said Dr. Beckman, a designated discussant for the report.
Among the 6,564 patients randomized in the study, about two-thirds underwent endovascular revascularization within 10 days before starting their study treatment, and the remaining third had undergone surgical revascularization. The study focused on patients “with symptomatic PAD but without known coronary artery disease,” noted Dr. Bonaca.
VOYAGER PAD trial
The VOYAGER PAD (Vascular Outcomes Study of Acetylsalicylic Acid Along With Rivaroxaban in Endovascular Or Surgical Limb Revascularization for Peripheral Artery Disease) trial enrolled patients during 2015-2018 at 534 sites in 34 countries. The study’s primary endpoint was a composite of acute limb ischemia, major amputation for vascular causes, myocardial infarction, ischemic stroke, or death from cardiovascular causes, and was reduced during a median follow-up of 28 months from 19.9% with aspirin alone to 17.3% on the combined regimen, a 2.6% absolute difference and a 15% relative risk reduction that was statistically significant, an endpoint primarily driven by a reduction in acute limb ischemia. The primary safety endpoint was the rate of TIMI (Thrombolysis in Myocardial Infarction) major bleeds, which was 0.8% higher in the patients who received the anticoagulant, a 43% relative increase that just missed statistical significance. But that result demonstrated the small but important increased risk for bleeding events that the dual regimen produced in these patients, Dr. Bonaca said. Simultaneously with his report the findings also appeared in an article published online (N Engl J Med. 2020 Mar 28. doi: 10.1056/NEJMoa2000052).
Dr. Bonaca cautioned that one limitation of his report on the primary outcome of VOYAGER PAD is that the results of an important subgroup analysis won’t be known until a second report during the ACC online sessions on March 29, which will examine the impact that treatment with the antiplatelet drug clopidogrel had on both the efficacy and safety outcomes. Half of the enrolled patients received clopidogrel at the discretion of their treating physicians; addition or exclusion of concurrent clopidogrel treatment was outside of the study’s design. “Is efficacy the same with or without clopidogrel, and what is the bleeding cost,” especially in patients who receive three antithrombotic drugs? “It will be very important to understand,” Dr. Bonaca said.
“Until now, we had no idea of what was the best antithrombotic strategy for patients after a successful peripheral vascular intervention.” VOYAGER PAD was “an unprecedented vascular study that addressed an unmet patient need,” commented Roxana Mehran, MD, a designated discussant for the study and professor of medicine and director of Interventional Cardiovascular Research at Mount Sinai Medical Center in New York.
VOYAGER PAD was sponsored by Bayer and Janssen, the companies that market rivaroxaban (Xarelto). The institution that Dr. Bonaca directs has received research funding from Bayer and Janssen, and also from Amgen, Aralez, AstraZeneca, Merck, Novo Nordisk, Pfizer, and Sanofi. Dr. Creager had no disclosures. Dr. Beckman has served as a data safety monitor for Bayer and for Novartis, and has been a consultant to Amgen, AstraZeneca, JanOne and Sanofi. Dr. Mehran has received research funding from Bayer and has been a consultant to Janssen, and she has also received research funding or been a consultant to several other companies.
SOURCE: Bonaca MP et al. ACC 20, Abstract 402-10.
A combined antithrombotic regimen of rivaroxaban plus aspirin was safe and effective for reducing ischemic events in patients with symptomatic peripheral artery disease who had just undergone peripheral artery revascularization in VOYAGER PAD, a multicenter randomized trial with nearly 6,600 patients.
The study and its results were a groundbreaking advance for this patient population, who until now have had no evidence-based treatment available, Mark P. Bonaca, MD, said on March 28 at the joint scientific sessions of the American College of Cardiology and the World Heart Federation. The meeting was conducted online after its cancellation because of the COVID-19 pandemic.
The study design excluded a small percentage of patients (about 2%) because of their very high bleeding-risk history. Among the treated patients, in those who received a combination of 2.5 mg rivaroxaban twice daily plus 100 mg of aspirin daily, bleeding events were more common, compared with control patients who received aspirin alone. But the patients who received both drugs showed no excess of fatal bleeds or intracranial hemorrhages, and the rate of ischemic events prevented by rivaroxaban plus aspirin exceeded the excess rate of bleeds by three- to sixfold, depending on how bleeding episodes were defined, noted Dr. Bonaca, executive director of CPC Clinical Research and CPC Community Health, an academic research organization affiliated with the University of Colorado at Denver in Aurora.
“This was a much anticipated and important trial. Those of us who treat patients with lower-limb peripheral artery disease have not had much evidence on how to treat these patients, particularly those who have just undergone revascularization. This trial gives us the evidence,” commented Mark A. Creager, MD, professor of medicine and director of the Heart and Vascular Center at Dartmouth-Hitchcock Medical Center in Lebanon, N.H. “The bleeding risk [from adding rivaroxaban treatment] was substantially less than the benefit from preventing major adverse limb events and major adverse cardiovascular events,” producing a “favorable balance” of benefit, compared with risk, Dr. Creager said in an interview. “In the right patients, the benefit greatly outweighed the risk.”
“This was an incredible trial that will advance care,” commented Joshua A. Beckman, MD, professor of medicine and director of Vascular Medicine at Vanderbilt University in Nashville, Tenn. “The treatment was beneficial for patients across a range of symptom severity, from claudication to critical limb ischemia,” and the results expand the range of patients proven to benefit from the rivaroxaban plus aspirin combination from the types of patients with peripheral artery disease (PAD) enrolled in the COMPASS trial. That pivotal trial showed similar benefit from the dual-antithrombotic regimen, but in patients who had both coronary artery disease as well as atherosclerotic disease in at least one additional vascular bed, such as lower-limb arteries (N Engl J Med. 2017 Oct 5;377[14]:1319-30). In addition to “bringing acute limb ischemia to the cardiovascular community,” the results also identified a very useful time point in the clinical presentation of these patients for starting a combined rivaroxaban plus aspirin regimen: when patients are hospitalized for their revascularization procedure, said Dr. Beckman, a designated discussant for the report.
Among the 6,564 patients randomized in the study, about two-thirds underwent endovascular revascularization within 10 days before starting their study treatment, and the remaining third had undergone surgical revascularization. The study focused on patients “with symptomatic PAD but without known coronary artery disease,” noted Dr. Bonaca.
VOYAGER PAD trial
The VOYAGER PAD (Vascular Outcomes Study of Acetylsalicylic Acid Along With Rivaroxaban in Endovascular Or Surgical Limb Revascularization for Peripheral Artery Disease) trial enrolled patients during 2015-2018 at 534 sites in 34 countries. The study’s primary endpoint was a composite of acute limb ischemia, major amputation for vascular causes, myocardial infarction, ischemic stroke, or death from cardiovascular causes, and was reduced during a median follow-up of 28 months from 19.9% with aspirin alone to 17.3% on the combined regimen, a 2.6% absolute difference and a 15% relative risk reduction that was statistically significant, an endpoint primarily driven by a reduction in acute limb ischemia. The primary safety endpoint was the rate of TIMI (Thrombolysis in Myocardial Infarction) major bleeds, which was 0.8% higher in the patients who received the anticoagulant, a 43% relative increase that just missed statistical significance. But that result demonstrated the small but important increased risk for bleeding events that the dual regimen produced in these patients, Dr. Bonaca said. Simultaneously with his report the findings also appeared in an article published online (N Engl J Med. 2020 Mar 28. doi: 10.1056/NEJMoa2000052).
Dr. Bonaca cautioned that one limitation of his report on the primary outcome of VOYAGER PAD is that the results of an important subgroup analysis won’t be known until a second report during the ACC online sessions on March 29, which will examine the impact that treatment with the antiplatelet drug clopidogrel had on both the efficacy and safety outcomes. Half of the enrolled patients received clopidogrel at the discretion of their treating physicians; addition or exclusion of concurrent clopidogrel treatment was outside of the study’s design. “Is efficacy the same with or without clopidogrel, and what is the bleeding cost,” especially in patients who receive three antithrombotic drugs? “It will be very important to understand,” Dr. Bonaca said.
“Until now, we had no idea of what was the best antithrombotic strategy for patients after a successful peripheral vascular intervention.” VOYAGER PAD was “an unprecedented vascular study that addressed an unmet patient need,” commented Roxana Mehran, MD, a designated discussant for the study and professor of medicine and director of Interventional Cardiovascular Research at Mount Sinai Medical Center in New York.
VOYAGER PAD was sponsored by Bayer and Janssen, the companies that market rivaroxaban (Xarelto). The institution that Dr. Bonaca directs has received research funding from Bayer and Janssen, and also from Amgen, Aralez, AstraZeneca, Merck, Novo Nordisk, Pfizer, and Sanofi. Dr. Creager had no disclosures. Dr. Beckman has served as a data safety monitor for Bayer and for Novartis, and has been a consultant to Amgen, AstraZeneca, JanOne and Sanofi. Dr. Mehran has received research funding from Bayer and has been a consultant to Janssen, and she has also received research funding or been a consultant to several other companies.
SOURCE: Bonaca MP et al. ACC 20, Abstract 402-10.
REPORTING FROM ACC 20
Key clinical point: Combined treatment with rivaroxaban plus aspirin safely reduced a composite measure of adverse ischemic events in PAD patients following lower-limb revascularization.
Major finding: The primary event outcome occurred in 17.3% of patients on rivaroxaban plus aspirin, and in 19.9% on aspirin alone.
Study details: VOYAGER PAD, a multicenter, international randomized trial with 6,564 patients.
Disclosures: VOYAGER PAD was sponsored by Bayer and Janssen, the companies that market rivaroxaban (Xarelto). The institution that Dr. Bonaca directs has received research funding from Bayer and Janssen, and also from Amgen, Aralez, AstraZeneca, Merck, Novo Nordisk, Pfizer, and Sanofi. Dr. Creager had no disclosures. Dr. Beckman has served as a data safety monitor for Bayer and for Novartis, and has been a consultant to Amgen, AstraZeneca, JanOne and Sanofi. Dr. Mehran has received research funding from Bayer and has been a consultant to Janssen, and she has also received research funding or been a consultant to several other companies.
Source: Bonaca MP. ACC 20, Abstract 402-10.
Benefit of ultrathin over thin stent still growing at 3 years
NATIONAL HARBOR, MD. – In a head-to-head comparison, the ultrathin-strut Orsiro drug-eluting stent (DES) is demonstrating a growing advantage over the thin-strut Xience DES stent in stable patients undergoing coronary revascularization, according to a presentation at the 2020 CRT meeting.
“These results direct our attention to strut thickness and polymer composition as key attributes for stent design,” reported David E. Kandzari, MD, director of interventional cardiology at the Piedmont Heart Institute in Atlanta.
In the multinational BIOFLOW V trial, 1,334 patients were randomized in a two-to-one ratio to the Orsiro stent, which is composed of a bioabsorbable, sirolimus-eluting polymer, or to the Xience stent, which is composed of an everolimus-eluting durable polymer. Relative to the Xience device, which has thin struts of 81 microns in width, the struts of the Orsiro device, at 60 microns in width, are characterized as ultrathin.
In earlier published follow-up studies, the ultrathin device demonstrated a lower rate of target lesion (TL) failure at 1 year (5.9% vs. 9.2%; P = .032) and at 2 years (7.1% vs. 11.1%; P = .015), but the 3-year data are notable because they indicate that the relative advantage is continuing to grow, according to Dr. Kandzari.
At 3 years, with follow-up available for 94.8% and 94.2% of the Orsiro and Xience groups, respectively, the absolute relative difference in the primary endpoint of TL failure reached 5.4% (8.2% vs. 13.6%; P = .002) in favor of the Orsiro device.
For the components of the composite TL failure endpoint, which includes cardiovascular death, TL-related myocardial infarction, and TL revascularization, there were large relative advantages for every outcome except cardiovascular death, which did not differ between the Orsiro and Xience groups (1.1% vs. 1.2%, respectively; P = .1). Conversely, the TL-related MI (5.5% vs. 10.1%; P = .004) and ischemia-driven TL revascularization (3.4% vs. 6.9%; P = .008) rates were nearly cut in half in the Orsiro arm.
“The benefit appears to be bimodal in that there is a significant advantage in the periprocedural period [for the Orsiro device] and then a late advantage,” Dr. Kandzari reported.
Most TL-related MI in both groups, for example, occurred within the first 30 days of follow-up. Although there was a relative advantage for the Orsiro device in this early period (4.1% vs. 6.7%; P = .04), Dr. Kandzari indicated that the advantage between 30 days and 3 years was even more impressive (0.95% vs. 2.8%; P = .012).
Dr. Kandzari, showing a graph in which the line representing Orsiro device hugged the x axis as the line for the Xience device climbed, emphasized that the rate of target vessel MI at the end of follow-up was nearly three times greater for those randomized to the Xience device.
The patterns of ischemia-driven TL revascularization also diverged. In this case, the rates over the first 360 days were very similar for the two devices initially. At 1 year, the lower rate in the Orsiro device was not significantly different (2.0% vs. 2.3%; P = .72), but the lines began to separate at about 18 months. By the end of 3 years, the rate of ischemia-related TL revascularization was nearly 70% lower in the Orsiro arm (1.5% vs. 4.7%; P < .001).
The Orsiro device was also linked with a lower rate of definite or probable stent thrombosis when the two devices were compared from 30 days post implantation to 3 years of follow-up (0.1% vs. 1.2%; P = .018).
Noting that there are several features of the Orsiro device that might explain these results, including the width of the struts, the biodegradable polymer, and the type of anti-inflammatory coating, Dr. Kandzari said that it is difficult to determine which attributes account for the overall or the specific advantages observed for the Orsiro device in the BIOFLOW V trial.
However, he hypothesized that “there might be different time lines for different benefits” related to individual device characteristics. For example, the ultrathin struts might be important for the early relative advantages while the biodegradation of the strut might explain the reduced need for revascularization.
Overall, “there is an emerging evidence base consistent across clinical trials demonstrating a potential efficacy and safety difference in favor of ultrathin struts,” according to Dr. Kandzari.
The data are “remarkable,” according to James B. Hermiller, MD, an interventional cardiologist at the Heart Center of Indiana in Indianapolis. A panel member for the CRT late-breaking trial session where these data were presented, Dr. Hermiller was impressed by the very low rate of revascularization in the extended follow-up.
“We have all wanted to see a flattening of these event curves after a year,” Dr. Hermiller said. He indicated that the BIOFLOW V data represent a departure from the need for revascularization and other late events so commonly seen over lengthening follow-up with earlier generation devices.
SOURCE: Kandzari DE. CRT 2020, Late Breaking Trials session S300.
NATIONAL HARBOR, MD. – In a head-to-head comparison, the ultrathin-strut Orsiro drug-eluting stent (DES) is demonstrating a growing advantage over the thin-strut Xience DES stent in stable patients undergoing coronary revascularization, according to a presentation at the 2020 CRT meeting.
“These results direct our attention to strut thickness and polymer composition as key attributes for stent design,” reported David E. Kandzari, MD, director of interventional cardiology at the Piedmont Heart Institute in Atlanta.
In the multinational BIOFLOW V trial, 1,334 patients were randomized in a two-to-one ratio to the Orsiro stent, which is composed of a bioabsorbable, sirolimus-eluting polymer, or to the Xience stent, which is composed of an everolimus-eluting durable polymer. Relative to the Xience device, which has thin struts of 81 microns in width, the struts of the Orsiro device, at 60 microns in width, are characterized as ultrathin.
In earlier published follow-up studies, the ultrathin device demonstrated a lower rate of target lesion (TL) failure at 1 year (5.9% vs. 9.2%; P = .032) and at 2 years (7.1% vs. 11.1%; P = .015), but the 3-year data are notable because they indicate that the relative advantage is continuing to grow, according to Dr. Kandzari.
At 3 years, with follow-up available for 94.8% and 94.2% of the Orsiro and Xience groups, respectively, the absolute relative difference in the primary endpoint of TL failure reached 5.4% (8.2% vs. 13.6%; P = .002) in favor of the Orsiro device.
For the components of the composite TL failure endpoint, which includes cardiovascular death, TL-related myocardial infarction, and TL revascularization, there were large relative advantages for every outcome except cardiovascular death, which did not differ between the Orsiro and Xience groups (1.1% vs. 1.2%, respectively; P = .1). Conversely, the TL-related MI (5.5% vs. 10.1%; P = .004) and ischemia-driven TL revascularization (3.4% vs. 6.9%; P = .008) rates were nearly cut in half in the Orsiro arm.
“The benefit appears to be bimodal in that there is a significant advantage in the periprocedural period [for the Orsiro device] and then a late advantage,” Dr. Kandzari reported.
Most TL-related MI in both groups, for example, occurred within the first 30 days of follow-up. Although there was a relative advantage for the Orsiro device in this early period (4.1% vs. 6.7%; P = .04), Dr. Kandzari indicated that the advantage between 30 days and 3 years was even more impressive (0.95% vs. 2.8%; P = .012).
Dr. Kandzari, showing a graph in which the line representing Orsiro device hugged the x axis as the line for the Xience device climbed, emphasized that the rate of target vessel MI at the end of follow-up was nearly three times greater for those randomized to the Xience device.
The patterns of ischemia-driven TL revascularization also diverged. In this case, the rates over the first 360 days were very similar for the two devices initially. At 1 year, the lower rate in the Orsiro device was not significantly different (2.0% vs. 2.3%; P = .72), but the lines began to separate at about 18 months. By the end of 3 years, the rate of ischemia-related TL revascularization was nearly 70% lower in the Orsiro arm (1.5% vs. 4.7%; P < .001).
The Orsiro device was also linked with a lower rate of definite or probable stent thrombosis when the two devices were compared from 30 days post implantation to 3 years of follow-up (0.1% vs. 1.2%; P = .018).
Noting that there are several features of the Orsiro device that might explain these results, including the width of the struts, the biodegradable polymer, and the type of anti-inflammatory coating, Dr. Kandzari said that it is difficult to determine which attributes account for the overall or the specific advantages observed for the Orsiro device in the BIOFLOW V trial.
However, he hypothesized that “there might be different time lines for different benefits” related to individual device characteristics. For example, the ultrathin struts might be important for the early relative advantages while the biodegradation of the strut might explain the reduced need for revascularization.
Overall, “there is an emerging evidence base consistent across clinical trials demonstrating a potential efficacy and safety difference in favor of ultrathin struts,” according to Dr. Kandzari.
The data are “remarkable,” according to James B. Hermiller, MD, an interventional cardiologist at the Heart Center of Indiana in Indianapolis. A panel member for the CRT late-breaking trial session where these data were presented, Dr. Hermiller was impressed by the very low rate of revascularization in the extended follow-up.
“We have all wanted to see a flattening of these event curves after a year,” Dr. Hermiller said. He indicated that the BIOFLOW V data represent a departure from the need for revascularization and other late events so commonly seen over lengthening follow-up with earlier generation devices.
SOURCE: Kandzari DE. CRT 2020, Late Breaking Trials session S300.
NATIONAL HARBOR, MD. – In a head-to-head comparison, the ultrathin-strut Orsiro drug-eluting stent (DES) is demonstrating a growing advantage over the thin-strut Xience DES stent in stable patients undergoing coronary revascularization, according to a presentation at the 2020 CRT meeting.
“These results direct our attention to strut thickness and polymer composition as key attributes for stent design,” reported David E. Kandzari, MD, director of interventional cardiology at the Piedmont Heart Institute in Atlanta.
In the multinational BIOFLOW V trial, 1,334 patients were randomized in a two-to-one ratio to the Orsiro stent, which is composed of a bioabsorbable, sirolimus-eluting polymer, or to the Xience stent, which is composed of an everolimus-eluting durable polymer. Relative to the Xience device, which has thin struts of 81 microns in width, the struts of the Orsiro device, at 60 microns in width, are characterized as ultrathin.
In earlier published follow-up studies, the ultrathin device demonstrated a lower rate of target lesion (TL) failure at 1 year (5.9% vs. 9.2%; P = .032) and at 2 years (7.1% vs. 11.1%; P = .015), but the 3-year data are notable because they indicate that the relative advantage is continuing to grow, according to Dr. Kandzari.
At 3 years, with follow-up available for 94.8% and 94.2% of the Orsiro and Xience groups, respectively, the absolute relative difference in the primary endpoint of TL failure reached 5.4% (8.2% vs. 13.6%; P = .002) in favor of the Orsiro device.
For the components of the composite TL failure endpoint, which includes cardiovascular death, TL-related myocardial infarction, and TL revascularization, there were large relative advantages for every outcome except cardiovascular death, which did not differ between the Orsiro and Xience groups (1.1% vs. 1.2%, respectively; P = .1). Conversely, the TL-related MI (5.5% vs. 10.1%; P = .004) and ischemia-driven TL revascularization (3.4% vs. 6.9%; P = .008) rates were nearly cut in half in the Orsiro arm.
“The benefit appears to be bimodal in that there is a significant advantage in the periprocedural period [for the Orsiro device] and then a late advantage,” Dr. Kandzari reported.
Most TL-related MI in both groups, for example, occurred within the first 30 days of follow-up. Although there was a relative advantage for the Orsiro device in this early period (4.1% vs. 6.7%; P = .04), Dr. Kandzari indicated that the advantage between 30 days and 3 years was even more impressive (0.95% vs. 2.8%; P = .012).
Dr. Kandzari, showing a graph in which the line representing Orsiro device hugged the x axis as the line for the Xience device climbed, emphasized that the rate of target vessel MI at the end of follow-up was nearly three times greater for those randomized to the Xience device.
The patterns of ischemia-driven TL revascularization also diverged. In this case, the rates over the first 360 days were very similar for the two devices initially. At 1 year, the lower rate in the Orsiro device was not significantly different (2.0% vs. 2.3%; P = .72), but the lines began to separate at about 18 months. By the end of 3 years, the rate of ischemia-related TL revascularization was nearly 70% lower in the Orsiro arm (1.5% vs. 4.7%; P < .001).
The Orsiro device was also linked with a lower rate of definite or probable stent thrombosis when the two devices were compared from 30 days post implantation to 3 years of follow-up (0.1% vs. 1.2%; P = .018).
Noting that there are several features of the Orsiro device that might explain these results, including the width of the struts, the biodegradable polymer, and the type of anti-inflammatory coating, Dr. Kandzari said that it is difficult to determine which attributes account for the overall or the specific advantages observed for the Orsiro device in the BIOFLOW V trial.
However, he hypothesized that “there might be different time lines for different benefits” related to individual device characteristics. For example, the ultrathin struts might be important for the early relative advantages while the biodegradation of the strut might explain the reduced need for revascularization.
Overall, “there is an emerging evidence base consistent across clinical trials demonstrating a potential efficacy and safety difference in favor of ultrathin struts,” according to Dr. Kandzari.
The data are “remarkable,” according to James B. Hermiller, MD, an interventional cardiologist at the Heart Center of Indiana in Indianapolis. A panel member for the CRT late-breaking trial session where these data were presented, Dr. Hermiller was impressed by the very low rate of revascularization in the extended follow-up.
“We have all wanted to see a flattening of these event curves after a year,” Dr. Hermiller said. He indicated that the BIOFLOW V data represent a departure from the need for revascularization and other late events so commonly seen over lengthening follow-up with earlier generation devices.
SOURCE: Kandzari DE. CRT 2020, Late Breaking Trials session S300.
REPORTING FROM CRT 2020
Childhood CV health tied to reduced risk later in life
Two observational studies link better cardiovascular health (CVH) in childhood and midlife to reduced CV mortality and subclinical atherosclerosis in later life. Though many studies have examined CVH and CV mortality in later life, the two studies, published in JAMA Cardiology, examine longitudinal CVH and could inform lifestyle modification.
Together, the studies lend support to the American Heart Association 2010 Strategic Initiative, which put an emphasis on health promotion in children rather than CV disease prevention, Erica Spatz, MD, of Yale University, New Haven, Conn., wrote in an accompanying editorial.
Dr. Spatz pointed out that CV disease prevention can be a tough sell, especially in younger patients for whom the threat of heart disease is distant. These studies and others like them could capture evolving risk factors through patients’ lives, and connect them to current lifestyle and experiences. Such data could overcome barriers to behavioral change and lead to more personalized interventions, she wrote.
Framingham Offspring Study
One study, led by Vanessa Xanthakis, PhD, of Boston University, examined the relationship between the length of time during midlife spent in ideal CVH and various CV disease and mortality outcomes at the final examination.
The prospective study included 1,445 participants (mean age 60 years, 52% women) from a Framingham Heart Study Offspring investigation based in Massachusetts. The subjects had completed seven examinations. The current study ranged from 1991 to 2015, and encompassed the fifth, sixth, and seventh examinations. Researchers calculated CVH scores based on resting blood pressure, height, weight, total cholesterol level, fasting blood glucose level, smoking status, diet, and physical activity.
At the seventh examination, 39% of participants had poor CVH scores and 54% had intermediate scores. For each 5-year period of intermediate or ideal CVH (compared with poor) measured in previous examinations, during the follow-up period after the seventh examination, there was an associated reduction in risk for adverse outcomes including incident hypertension (hazard ratio, 0.67; 95% confidence interval, 056-0.80), diabetes (HR, 0.73; 95% CI, 0.57-0.93), chronic kidney disease (HR, 0.75; 95% CI, 0.63-0.89), CV disease (HR, 0.73; 95% CI, 0.63-0.85), and all-cause mortality (HR, 0.86; 95% CI, 0.76-0.97).
“Our results indicated that living longer in adulthood with better CVH may be potentially beneficial regardless of age because we did not observe statistically significant effect modification by age of the associations between duration in a given CVH score category and any outcome. Overall, our findings support the importance of promoting healthy behaviors throughout the life course,” the authors wrote.
The study was limited by several factors. Diet and physical activity were self-reported, and about half of participants were excluded after missing an examination, which could introduce bias.
International cohort study
The second study analyzed data from 9,388 individuals in five prospective cohorts in the United States and Finland. During 1973-2015, it tracked participants from childhood through middle age (age 8-55 years), linking CVH measures to subclinical atherosclerosis as measured by carotid intima-media thickness (cIMT) in middle age. Led by Norrina Allen, PhD, of the Northwestern University, Chicago, the researchers measured body mass index, total cholesterol level, blood pressure, glucose level, diet, physical activity, and smoking status during a minimum of three examinations. Based on those data, they classified participants as having ideal, intermediate, or poor CVH.
The researchers grouped the participants into five CVH trajectories: High-late decline, which started with high CVH scores at age 8 and maintained them through early adulthood (16%); high-moderate decline (high early scores, moderate decline; 26%); high-early decline (high early scores, early-life decline; 32%); intermediate-late decline (intermediate initial scores, late decline; 16%); and intermediate-early decline (10%). CVH stratification began early: At age 8, 25% of individuals had intermediate CVH scores.
After adjustment for demographics and baseline smoking, diet, and physical activity, the high-late decline CVH group had the smallest mean cIMT value (0.64 mm; 95 % CI, 0.63-0.65 mm), while the intermediate-early decline group, which had the poorest CVH, had the largest (0.72 mm; 95% CI, 0.69-0.76 mm; P less than .001). The relationship was the same even after adjustment for baseline or proximal CVH scores, showing that the trajectory of CVH scores was driving the measure of subclinical atherosclerosis.
“Although it remains important to provide treatment to individuals with elevated risk factor levels, the most effective way to reduce the burden of future CV disease may be to prevent the development of those CV disease risk factors, an approach termed primordial prevention. There is a large body of literature showing effective interventions that may help individuals maintain ideal CV health. Our findings suggest that these interventions are critical and should be implemented early in life to prevent the loss of CVH and future CV [disease] development,” the authors wrote.
The study’s limitations include the fact that analyzed cohorts were drawn from studies with varying protocols and CVH measurement methods. It is also limited by its observational nature.
The two studies were funded by a range of nonindustry sources.
SOURCES: Allen N et al. JAMA Cardiol. 2020 Mar 11. doi: 10.1001/jamacardio.2020.0140; Corlin N et al. JAMA Cardiol. 2020 Mar 11. doi: 10.1001/jamacardio.2020.0109.
Two observational studies link better cardiovascular health (CVH) in childhood and midlife to reduced CV mortality and subclinical atherosclerosis in later life. Though many studies have examined CVH and CV mortality in later life, the two studies, published in JAMA Cardiology, examine longitudinal CVH and could inform lifestyle modification.
Together, the studies lend support to the American Heart Association 2010 Strategic Initiative, which put an emphasis on health promotion in children rather than CV disease prevention, Erica Spatz, MD, of Yale University, New Haven, Conn., wrote in an accompanying editorial.
Dr. Spatz pointed out that CV disease prevention can be a tough sell, especially in younger patients for whom the threat of heart disease is distant. These studies and others like them could capture evolving risk factors through patients’ lives, and connect them to current lifestyle and experiences. Such data could overcome barriers to behavioral change and lead to more personalized interventions, she wrote.
Framingham Offspring Study
One study, led by Vanessa Xanthakis, PhD, of Boston University, examined the relationship between the length of time during midlife spent in ideal CVH and various CV disease and mortality outcomes at the final examination.
The prospective study included 1,445 participants (mean age 60 years, 52% women) from a Framingham Heart Study Offspring investigation based in Massachusetts. The subjects had completed seven examinations. The current study ranged from 1991 to 2015, and encompassed the fifth, sixth, and seventh examinations. Researchers calculated CVH scores based on resting blood pressure, height, weight, total cholesterol level, fasting blood glucose level, smoking status, diet, and physical activity.
At the seventh examination, 39% of participants had poor CVH scores and 54% had intermediate scores. For each 5-year period of intermediate or ideal CVH (compared with poor) measured in previous examinations, during the follow-up period after the seventh examination, there was an associated reduction in risk for adverse outcomes including incident hypertension (hazard ratio, 0.67; 95% confidence interval, 056-0.80), diabetes (HR, 0.73; 95% CI, 0.57-0.93), chronic kidney disease (HR, 0.75; 95% CI, 0.63-0.89), CV disease (HR, 0.73; 95% CI, 0.63-0.85), and all-cause mortality (HR, 0.86; 95% CI, 0.76-0.97).
“Our results indicated that living longer in adulthood with better CVH may be potentially beneficial regardless of age because we did not observe statistically significant effect modification by age of the associations between duration in a given CVH score category and any outcome. Overall, our findings support the importance of promoting healthy behaviors throughout the life course,” the authors wrote.
The study was limited by several factors. Diet and physical activity were self-reported, and about half of participants were excluded after missing an examination, which could introduce bias.
International cohort study
The second study analyzed data from 9,388 individuals in five prospective cohorts in the United States and Finland. During 1973-2015, it tracked participants from childhood through middle age (age 8-55 years), linking CVH measures to subclinical atherosclerosis as measured by carotid intima-media thickness (cIMT) in middle age. Led by Norrina Allen, PhD, of the Northwestern University, Chicago, the researchers measured body mass index, total cholesterol level, blood pressure, glucose level, diet, physical activity, and smoking status during a minimum of three examinations. Based on those data, they classified participants as having ideal, intermediate, or poor CVH.
The researchers grouped the participants into five CVH trajectories: High-late decline, which started with high CVH scores at age 8 and maintained them through early adulthood (16%); high-moderate decline (high early scores, moderate decline; 26%); high-early decline (high early scores, early-life decline; 32%); intermediate-late decline (intermediate initial scores, late decline; 16%); and intermediate-early decline (10%). CVH stratification began early: At age 8, 25% of individuals had intermediate CVH scores.
After adjustment for demographics and baseline smoking, diet, and physical activity, the high-late decline CVH group had the smallest mean cIMT value (0.64 mm; 95 % CI, 0.63-0.65 mm), while the intermediate-early decline group, which had the poorest CVH, had the largest (0.72 mm; 95% CI, 0.69-0.76 mm; P less than .001). The relationship was the same even after adjustment for baseline or proximal CVH scores, showing that the trajectory of CVH scores was driving the measure of subclinical atherosclerosis.
“Although it remains important to provide treatment to individuals with elevated risk factor levels, the most effective way to reduce the burden of future CV disease may be to prevent the development of those CV disease risk factors, an approach termed primordial prevention. There is a large body of literature showing effective interventions that may help individuals maintain ideal CV health. Our findings suggest that these interventions are critical and should be implemented early in life to prevent the loss of CVH and future CV [disease] development,” the authors wrote.
The study’s limitations include the fact that analyzed cohorts were drawn from studies with varying protocols and CVH measurement methods. It is also limited by its observational nature.
The two studies were funded by a range of nonindustry sources.
SOURCES: Allen N et al. JAMA Cardiol. 2020 Mar 11. doi: 10.1001/jamacardio.2020.0140; Corlin N et al. JAMA Cardiol. 2020 Mar 11. doi: 10.1001/jamacardio.2020.0109.
Two observational studies link better cardiovascular health (CVH) in childhood and midlife to reduced CV mortality and subclinical atherosclerosis in later life. Though many studies have examined CVH and CV mortality in later life, the two studies, published in JAMA Cardiology, examine longitudinal CVH and could inform lifestyle modification.
Together, the studies lend support to the American Heart Association 2010 Strategic Initiative, which put an emphasis on health promotion in children rather than CV disease prevention, Erica Spatz, MD, of Yale University, New Haven, Conn., wrote in an accompanying editorial.
Dr. Spatz pointed out that CV disease prevention can be a tough sell, especially in younger patients for whom the threat of heart disease is distant. These studies and others like them could capture evolving risk factors through patients’ lives, and connect them to current lifestyle and experiences. Such data could overcome barriers to behavioral change and lead to more personalized interventions, she wrote.
Framingham Offspring Study
One study, led by Vanessa Xanthakis, PhD, of Boston University, examined the relationship between the length of time during midlife spent in ideal CVH and various CV disease and mortality outcomes at the final examination.
The prospective study included 1,445 participants (mean age 60 years, 52% women) from a Framingham Heart Study Offspring investigation based in Massachusetts. The subjects had completed seven examinations. The current study ranged from 1991 to 2015, and encompassed the fifth, sixth, and seventh examinations. Researchers calculated CVH scores based on resting blood pressure, height, weight, total cholesterol level, fasting blood glucose level, smoking status, diet, and physical activity.
At the seventh examination, 39% of participants had poor CVH scores and 54% had intermediate scores. For each 5-year period of intermediate or ideal CVH (compared with poor) measured in previous examinations, during the follow-up period after the seventh examination, there was an associated reduction in risk for adverse outcomes including incident hypertension (hazard ratio, 0.67; 95% confidence interval, 056-0.80), diabetes (HR, 0.73; 95% CI, 0.57-0.93), chronic kidney disease (HR, 0.75; 95% CI, 0.63-0.89), CV disease (HR, 0.73; 95% CI, 0.63-0.85), and all-cause mortality (HR, 0.86; 95% CI, 0.76-0.97).
“Our results indicated that living longer in adulthood with better CVH may be potentially beneficial regardless of age because we did not observe statistically significant effect modification by age of the associations between duration in a given CVH score category and any outcome. Overall, our findings support the importance of promoting healthy behaviors throughout the life course,” the authors wrote.
The study was limited by several factors. Diet and physical activity were self-reported, and about half of participants were excluded after missing an examination, which could introduce bias.
International cohort study
The second study analyzed data from 9,388 individuals in five prospective cohorts in the United States and Finland. During 1973-2015, it tracked participants from childhood through middle age (age 8-55 years), linking CVH measures to subclinical atherosclerosis as measured by carotid intima-media thickness (cIMT) in middle age. Led by Norrina Allen, PhD, of the Northwestern University, Chicago, the researchers measured body mass index, total cholesterol level, blood pressure, glucose level, diet, physical activity, and smoking status during a minimum of three examinations. Based on those data, they classified participants as having ideal, intermediate, or poor CVH.
The researchers grouped the participants into five CVH trajectories: High-late decline, which started with high CVH scores at age 8 and maintained them through early adulthood (16%); high-moderate decline (high early scores, moderate decline; 26%); high-early decline (high early scores, early-life decline; 32%); intermediate-late decline (intermediate initial scores, late decline; 16%); and intermediate-early decline (10%). CVH stratification began early: At age 8, 25% of individuals had intermediate CVH scores.
After adjustment for demographics and baseline smoking, diet, and physical activity, the high-late decline CVH group had the smallest mean cIMT value (0.64 mm; 95 % CI, 0.63-0.65 mm), while the intermediate-early decline group, which had the poorest CVH, had the largest (0.72 mm; 95% CI, 0.69-0.76 mm; P less than .001). The relationship was the same even after adjustment for baseline or proximal CVH scores, showing that the trajectory of CVH scores was driving the measure of subclinical atherosclerosis.
“Although it remains important to provide treatment to individuals with elevated risk factor levels, the most effective way to reduce the burden of future CV disease may be to prevent the development of those CV disease risk factors, an approach termed primordial prevention. There is a large body of literature showing effective interventions that may help individuals maintain ideal CV health. Our findings suggest that these interventions are critical and should be implemented early in life to prevent the loss of CVH and future CV [disease] development,” the authors wrote.
The study’s limitations include the fact that analyzed cohorts were drawn from studies with varying protocols and CVH measurement methods. It is also limited by its observational nature.
The two studies were funded by a range of nonindustry sources.
SOURCES: Allen N et al. JAMA Cardiol. 2020 Mar 11. doi: 10.1001/jamacardio.2020.0140; Corlin N et al. JAMA Cardiol. 2020 Mar 11. doi: 10.1001/jamacardio.2020.0109.
FROM JAMA CARDIOLOGY
Red meat intake linked to increased risk of fatal CHD in men
PHOENIX – Consumption of red meat, particularly the processed form, is linked to a higher risk of developing coronary heart disease in men, results from a large prospective analysis demonstrated.
“The findings of this study are in line with randomized trials showing that the consumption of red meat, as compared with plant-based protein sources, increases LDL cholesterol levels, and with previous studies on red meat and risk of coronary heart disease,” lead study author Laila Al-Shaar, MPH, PhD, said in an interview in advance of the Epidemiology and Prevention/Lifestyle and Cardiometabolic Health meeting.
According to Dr. Al-Shaar, a postdoctoral research fellow in the department of nutrition at the T.H. Chan School of Public Health at Harvard University, Boston, most of the existing studies on red meat and heart disease have examined the impact of increasing consumption of red meat while decreasing consumption of all other foods. For the current study, she and her colleagues used a substitution analysis approach to understand how replacing red meat (total, processed, or unprocessed) with another protein-rich food was associated with the risk of heart disease. “This would potentially provide more specific guidance for healthier alternatives for those planning to cut down their red meat intake,” she said.
She and her colleagues prospectively followed 43,259 men in the Health Professionals Follow-up Study (1986-2012) who had no known history of cancer or cardiovascular disease. Diet was assessed by a standardized and validated food frequency questionnaire that was updated every 4 years. Dr. Al-Shaar and her colleagues used multivariate Cox models to estimate hazard ratios and 95% confidence intervals of CHD risk across categories of red meat consumption. They performed substitution analyses by comparing coefficients in models including alternative foods as continuous variables.
Over roughly 933,000 person-years of follow-up, the researchers documented 4,148 incident CHD cases. Of these, 1,680 were fatal. After multivariate adjustment for dietary and nondietary risk factors, both total and processed red meat intake were associated with a modestly higher risk of CHD (hazard ratio for a one serving/day increment, 1.08; 95% confidence interval, 1.01-1.14 for total red meat; and HR, 1.13; 95% CI, 1.03-1.22 for processed red meat). Substitutions of one serving per day of other foods (including nuts, legumes, soy, whole grains, and low- and high-fat dairy) for one serving per day of total red meat were associated with a 10%-47% lower CHD risk.
Stronger inverse associations were observed between some of these substitutions for red meat and risk of fatal CHD. Substituting nuts lowered the risk of fatal heart disease by 17%, while replacing red meat with whole grains was linked to a 48% reduction in that outcome. Those associations were more pronounced when replacing processed red meat.
“Processed meats and meats in general have been thought to be potentially not favorable in terms of cardiovascular disease and cardiovascular disease risk,” Robert H. Eckel, MD, professor emeritus of medicine at the University of Colorado Anschutz Medical Campus, Aurora, said in an interview. “Now we have increasing data that not only is there a negative cardiovascular disease impact of animal protein, but we see this on all-cause mortality, including cancer.”
Dr. Al-Shaar said that the findings “support current recommendations to limit consumption of red meat and suggest that high-quality plant-based proteins such as nuts, legumes, and soy are good alternatives for individuals planning to have better food choices and healthier eating patterns.”
She acknowledged certain limitations of the study, including its observational design and the fact that it was limited to non-Hispanic white health professionals, “thus limiting the generalizability of its findings to the whole population.”
Dr. Eckel, who is a past president of the American Heart Association, underscored the importance of one’s overall diet in mitigating the risk of developing coronary heart disease. “It’s not simply substituting animal protein with plant protein,” he said. “Fruits and vegetables and whole grains, lean protein from fish – a Mediterranean-style diet – is what the AHA recommends.”
Dr. Al-Shaar reported having no financial disclosures. The study was supported by a T32 training grant from the National Institutes of Health and by other grants from the NIH. The meeting was sponsored by the AHA.
SOURCE: Al-Shaar L et al. Epi/Lifestyle 2020, Abstract P512.
PHOENIX – Consumption of red meat, particularly the processed form, is linked to a higher risk of developing coronary heart disease in men, results from a large prospective analysis demonstrated.
“The findings of this study are in line with randomized trials showing that the consumption of red meat, as compared with plant-based protein sources, increases LDL cholesterol levels, and with previous studies on red meat and risk of coronary heart disease,” lead study author Laila Al-Shaar, MPH, PhD, said in an interview in advance of the Epidemiology and Prevention/Lifestyle and Cardiometabolic Health meeting.
According to Dr. Al-Shaar, a postdoctoral research fellow in the department of nutrition at the T.H. Chan School of Public Health at Harvard University, Boston, most of the existing studies on red meat and heart disease have examined the impact of increasing consumption of red meat while decreasing consumption of all other foods. For the current study, she and her colleagues used a substitution analysis approach to understand how replacing red meat (total, processed, or unprocessed) with another protein-rich food was associated with the risk of heart disease. “This would potentially provide more specific guidance for healthier alternatives for those planning to cut down their red meat intake,” she said.
She and her colleagues prospectively followed 43,259 men in the Health Professionals Follow-up Study (1986-2012) who had no known history of cancer or cardiovascular disease. Diet was assessed by a standardized and validated food frequency questionnaire that was updated every 4 years. Dr. Al-Shaar and her colleagues used multivariate Cox models to estimate hazard ratios and 95% confidence intervals of CHD risk across categories of red meat consumption. They performed substitution analyses by comparing coefficients in models including alternative foods as continuous variables.
Over roughly 933,000 person-years of follow-up, the researchers documented 4,148 incident CHD cases. Of these, 1,680 were fatal. After multivariate adjustment for dietary and nondietary risk factors, both total and processed red meat intake were associated with a modestly higher risk of CHD (hazard ratio for a one serving/day increment, 1.08; 95% confidence interval, 1.01-1.14 for total red meat; and HR, 1.13; 95% CI, 1.03-1.22 for processed red meat). Substitutions of one serving per day of other foods (including nuts, legumes, soy, whole grains, and low- and high-fat dairy) for one serving per day of total red meat were associated with a 10%-47% lower CHD risk.
Stronger inverse associations were observed between some of these substitutions for red meat and risk of fatal CHD. Substituting nuts lowered the risk of fatal heart disease by 17%, while replacing red meat with whole grains was linked to a 48% reduction in that outcome. Those associations were more pronounced when replacing processed red meat.
“Processed meats and meats in general have been thought to be potentially not favorable in terms of cardiovascular disease and cardiovascular disease risk,” Robert H. Eckel, MD, professor emeritus of medicine at the University of Colorado Anschutz Medical Campus, Aurora, said in an interview. “Now we have increasing data that not only is there a negative cardiovascular disease impact of animal protein, but we see this on all-cause mortality, including cancer.”
Dr. Al-Shaar said that the findings “support current recommendations to limit consumption of red meat and suggest that high-quality plant-based proteins such as nuts, legumes, and soy are good alternatives for individuals planning to have better food choices and healthier eating patterns.”
She acknowledged certain limitations of the study, including its observational design and the fact that it was limited to non-Hispanic white health professionals, “thus limiting the generalizability of its findings to the whole population.”
Dr. Eckel, who is a past president of the American Heart Association, underscored the importance of one’s overall diet in mitigating the risk of developing coronary heart disease. “It’s not simply substituting animal protein with plant protein,” he said. “Fruits and vegetables and whole grains, lean protein from fish – a Mediterranean-style diet – is what the AHA recommends.”
Dr. Al-Shaar reported having no financial disclosures. The study was supported by a T32 training grant from the National Institutes of Health and by other grants from the NIH. The meeting was sponsored by the AHA.
SOURCE: Al-Shaar L et al. Epi/Lifestyle 2020, Abstract P512.
PHOENIX – Consumption of red meat, particularly the processed form, is linked to a higher risk of developing coronary heart disease in men, results from a large prospective analysis demonstrated.
“The findings of this study are in line with randomized trials showing that the consumption of red meat, as compared with plant-based protein sources, increases LDL cholesterol levels, and with previous studies on red meat and risk of coronary heart disease,” lead study author Laila Al-Shaar, MPH, PhD, said in an interview in advance of the Epidemiology and Prevention/Lifestyle and Cardiometabolic Health meeting.
According to Dr. Al-Shaar, a postdoctoral research fellow in the department of nutrition at the T.H. Chan School of Public Health at Harvard University, Boston, most of the existing studies on red meat and heart disease have examined the impact of increasing consumption of red meat while decreasing consumption of all other foods. For the current study, she and her colleagues used a substitution analysis approach to understand how replacing red meat (total, processed, or unprocessed) with another protein-rich food was associated with the risk of heart disease. “This would potentially provide more specific guidance for healthier alternatives for those planning to cut down their red meat intake,” she said.
She and her colleagues prospectively followed 43,259 men in the Health Professionals Follow-up Study (1986-2012) who had no known history of cancer or cardiovascular disease. Diet was assessed by a standardized and validated food frequency questionnaire that was updated every 4 years. Dr. Al-Shaar and her colleagues used multivariate Cox models to estimate hazard ratios and 95% confidence intervals of CHD risk across categories of red meat consumption. They performed substitution analyses by comparing coefficients in models including alternative foods as continuous variables.
Over roughly 933,000 person-years of follow-up, the researchers documented 4,148 incident CHD cases. Of these, 1,680 were fatal. After multivariate adjustment for dietary and nondietary risk factors, both total and processed red meat intake were associated with a modestly higher risk of CHD (hazard ratio for a one serving/day increment, 1.08; 95% confidence interval, 1.01-1.14 for total red meat; and HR, 1.13; 95% CI, 1.03-1.22 for processed red meat). Substitutions of one serving per day of other foods (including nuts, legumes, soy, whole grains, and low- and high-fat dairy) for one serving per day of total red meat were associated with a 10%-47% lower CHD risk.
Stronger inverse associations were observed between some of these substitutions for red meat and risk of fatal CHD. Substituting nuts lowered the risk of fatal heart disease by 17%, while replacing red meat with whole grains was linked to a 48% reduction in that outcome. Those associations were more pronounced when replacing processed red meat.
“Processed meats and meats in general have been thought to be potentially not favorable in terms of cardiovascular disease and cardiovascular disease risk,” Robert H. Eckel, MD, professor emeritus of medicine at the University of Colorado Anschutz Medical Campus, Aurora, said in an interview. “Now we have increasing data that not only is there a negative cardiovascular disease impact of animal protein, but we see this on all-cause mortality, including cancer.”
Dr. Al-Shaar said that the findings “support current recommendations to limit consumption of red meat and suggest that high-quality plant-based proteins such as nuts, legumes, and soy are good alternatives for individuals planning to have better food choices and healthier eating patterns.”
She acknowledged certain limitations of the study, including its observational design and the fact that it was limited to non-Hispanic white health professionals, “thus limiting the generalizability of its findings to the whole population.”
Dr. Eckel, who is a past president of the American Heart Association, underscored the importance of one’s overall diet in mitigating the risk of developing coronary heart disease. “It’s not simply substituting animal protein with plant protein,” he said. “Fruits and vegetables and whole grains, lean protein from fish – a Mediterranean-style diet – is what the AHA recommends.”
Dr. Al-Shaar reported having no financial disclosures. The study was supported by a T32 training grant from the National Institutes of Health and by other grants from the NIH. The meeting was sponsored by the AHA.
SOURCE: Al-Shaar L et al. Epi/Lifestyle 2020, Abstract P512.
REPORTING FROM EPI/LIFESTYLE 2020
Gender, racial disparities persist in statin use by ASCVD patients
PHOENIX – Statin use for the secondary prevention of cardiovascular disease increased modestly between 2008 and 2017 in the United States, but more than 40% of patients with established atherosclerotic cardiovascular disease are still not on a statin.
In addition, even after release of the 2013 American College of Cardiology/American Heart Association Guideline on the Treatment of Blood Cholesterol to Reduce Atherosclerotic Cardiovascular Risk in Adults (Circulation. 2014;129:S1-45) that markedly increased the pool of eligible patients, disparities exist in the proportion of women versus men, and blacks and Hispanics versus whites with atherosclerotic cardiovascular disease (ASCVD) who are currently receiving a statin.
“Despite repeated calls for the use of statins for secondary prevention of CVD in multiple guidelines, gender and racial inequalities in the use of statins persist,” Joseph A. Salami, MD, MPH, said at the Epidemiology and Prevention/Lifestyle and Cardiometabolic Health meeting, sponsored by the American Heart Association. “Cardiovascular disease remains the leading cause of death in the U.S. In 2017, it was responsible for 647,457 deaths. We have an opportunity to improve CVD-related outcomes and cost by intensifying efforts to use statins for the secondary prevention of CVD and closing gender and racial gaps. Action is needed.”
Dr. Salami, a biostatistician with the Baptist Health South Florida Center for Advanced Analytics in Coral Gables, based his remarks on an analysis of data contained in the 2008-2017 Medical Expenditure Panel Survey (MEPS), a national representative survey sponsored by the Agency for Healthcare Research and Quality. “Between 2013 and 2018 there were six different guidelines released encouraging statin use among ASCVD patients,” he said. “Besides the good number needed to treat, statin use on secondary prevention of CVD is cost effective.”
Given the proven efficacy of statin use in the prevention of CVD, he and his associates set out to examine trends in the proportion of adults with ASCVD using statins and to assess for gender and racial differences in their use. The researchers used ICD-9 and ICD-10 codes to define ASCVD among the MEPS study population, as well as self-reported history of coronary artery disease, peripheral artery disease, and stroke. After excluding adults aged younger than 40 years and those without ASCVD, this left a population of 15,911 patients. Of these, 44% were female, their mean age was 62 years, and 72% were Caucasian.
Overall, statin use increased from 50% in 2008 to 58.7% in 2017, with an average annual percentage change of 0.95% between 2010 and 2017 (P = .01). However, the annual percentage change in statin use was 0.25% among men versus 0.14% among women (P = .022). “Each year during the study period, more than 3 million women with ASCVD were not prescribed a statin, which translated into about 36 million adult-years,” Dr. Salami said. “In 2017, 16% of these women were African Americans and 15% were Hispanic.”
Logistic regression analysis revealed that in 2017, females with ASCVD were less likely to be prescribed a statin, compared with males (odds ratio, 0.52; P less than .001). In addition, compared with whites, blacks were less likely to be prescribed a statin (OR, 0.69; P = .012), as were Hispanics (OR, 0.62; P = .003). “In a multivariate logistic regression controlling for age, health insurance status, and comorbidities, the gender disparity remained statistically significant, but the racial disparity did not,” Dr. Salami said.
In an interview, one of the meeting session’s moderators, Sherry-Ann Brown, MD, PhD, characterized the study’s findings as sobering. “This should be an eye-opener for all of us in medicine, whether we are physicians, pharmacists, nurses, or researchers,” said Dr. Brown, who is a cardiologist and physician scientist at the Mayo Clinic in Rochester, Minn. “We’re all in this together, and we all have a role to play in addressing social determinants of health. I think we need to recognize the fact that we’re not treating blacks, Hispanics, and women to the degree that we should be, compared to whites and men. I think we need to do better, and we need to figure out how to reach that population, and how to improve.”
Dr. Salami acknowledged certain limitations of the study, including the fact that MEPS was carried out in a noninstitutionalized adult population and that the definition of ASCVD was based partly on self-report. “Therefore, an underestimation of number adults with ASCVD is likely,” he said. “We also couldn’t determine adherence to medication nor long-term use of statins among adults with ASCVD.”
He concluded his presentation by noting that, over the 10-year study period, there were about 71.2 million ASCVD adult-years without a statin prescription. “That is a staggering number,” Dr. Salami said.
He reported having no financial disclosures.
SOURCE: Salami A et al. Epi/Lifestyle 2020, Abstract 4.
PHOENIX – Statin use for the secondary prevention of cardiovascular disease increased modestly between 2008 and 2017 in the United States, but more than 40% of patients with established atherosclerotic cardiovascular disease are still not on a statin.
In addition, even after release of the 2013 American College of Cardiology/American Heart Association Guideline on the Treatment of Blood Cholesterol to Reduce Atherosclerotic Cardiovascular Risk in Adults (Circulation. 2014;129:S1-45) that markedly increased the pool of eligible patients, disparities exist in the proportion of women versus men, and blacks and Hispanics versus whites with atherosclerotic cardiovascular disease (ASCVD) who are currently receiving a statin.
“Despite repeated calls for the use of statins for secondary prevention of CVD in multiple guidelines, gender and racial inequalities in the use of statins persist,” Joseph A. Salami, MD, MPH, said at the Epidemiology and Prevention/Lifestyle and Cardiometabolic Health meeting, sponsored by the American Heart Association. “Cardiovascular disease remains the leading cause of death in the U.S. In 2017, it was responsible for 647,457 deaths. We have an opportunity to improve CVD-related outcomes and cost by intensifying efforts to use statins for the secondary prevention of CVD and closing gender and racial gaps. Action is needed.”
Dr. Salami, a biostatistician with the Baptist Health South Florida Center for Advanced Analytics in Coral Gables, based his remarks on an analysis of data contained in the 2008-2017 Medical Expenditure Panel Survey (MEPS), a national representative survey sponsored by the Agency for Healthcare Research and Quality. “Between 2013 and 2018 there were six different guidelines released encouraging statin use among ASCVD patients,” he said. “Besides the good number needed to treat, statin use on secondary prevention of CVD is cost effective.”
Given the proven efficacy of statin use in the prevention of CVD, he and his associates set out to examine trends in the proportion of adults with ASCVD using statins and to assess for gender and racial differences in their use. The researchers used ICD-9 and ICD-10 codes to define ASCVD among the MEPS study population, as well as self-reported history of coronary artery disease, peripheral artery disease, and stroke. After excluding adults aged younger than 40 years and those without ASCVD, this left a population of 15,911 patients. Of these, 44% were female, their mean age was 62 years, and 72% were Caucasian.
Overall, statin use increased from 50% in 2008 to 58.7% in 2017, with an average annual percentage change of 0.95% between 2010 and 2017 (P = .01). However, the annual percentage change in statin use was 0.25% among men versus 0.14% among women (P = .022). “Each year during the study period, more than 3 million women with ASCVD were not prescribed a statin, which translated into about 36 million adult-years,” Dr. Salami said. “In 2017, 16% of these women were African Americans and 15% were Hispanic.”
Logistic regression analysis revealed that in 2017, females with ASCVD were less likely to be prescribed a statin, compared with males (odds ratio, 0.52; P less than .001). In addition, compared with whites, blacks were less likely to be prescribed a statin (OR, 0.69; P = .012), as were Hispanics (OR, 0.62; P = .003). “In a multivariate logistic regression controlling for age, health insurance status, and comorbidities, the gender disparity remained statistically significant, but the racial disparity did not,” Dr. Salami said.
In an interview, one of the meeting session’s moderators, Sherry-Ann Brown, MD, PhD, characterized the study’s findings as sobering. “This should be an eye-opener for all of us in medicine, whether we are physicians, pharmacists, nurses, or researchers,” said Dr. Brown, who is a cardiologist and physician scientist at the Mayo Clinic in Rochester, Minn. “We’re all in this together, and we all have a role to play in addressing social determinants of health. I think we need to recognize the fact that we’re not treating blacks, Hispanics, and women to the degree that we should be, compared to whites and men. I think we need to do better, and we need to figure out how to reach that population, and how to improve.”
Dr. Salami acknowledged certain limitations of the study, including the fact that MEPS was carried out in a noninstitutionalized adult population and that the definition of ASCVD was based partly on self-report. “Therefore, an underestimation of number adults with ASCVD is likely,” he said. “We also couldn’t determine adherence to medication nor long-term use of statins among adults with ASCVD.”
He concluded his presentation by noting that, over the 10-year study period, there were about 71.2 million ASCVD adult-years without a statin prescription. “That is a staggering number,” Dr. Salami said.
He reported having no financial disclosures.
SOURCE: Salami A et al. Epi/Lifestyle 2020, Abstract 4.
PHOENIX – Statin use for the secondary prevention of cardiovascular disease increased modestly between 2008 and 2017 in the United States, but more than 40% of patients with established atherosclerotic cardiovascular disease are still not on a statin.
In addition, even after release of the 2013 American College of Cardiology/American Heart Association Guideline on the Treatment of Blood Cholesterol to Reduce Atherosclerotic Cardiovascular Risk in Adults (Circulation. 2014;129:S1-45) that markedly increased the pool of eligible patients, disparities exist in the proportion of women versus men, and blacks and Hispanics versus whites with atherosclerotic cardiovascular disease (ASCVD) who are currently receiving a statin.
“Despite repeated calls for the use of statins for secondary prevention of CVD in multiple guidelines, gender and racial inequalities in the use of statins persist,” Joseph A. Salami, MD, MPH, said at the Epidemiology and Prevention/Lifestyle and Cardiometabolic Health meeting, sponsored by the American Heart Association. “Cardiovascular disease remains the leading cause of death in the U.S. In 2017, it was responsible for 647,457 deaths. We have an opportunity to improve CVD-related outcomes and cost by intensifying efforts to use statins for the secondary prevention of CVD and closing gender and racial gaps. Action is needed.”
Dr. Salami, a biostatistician with the Baptist Health South Florida Center for Advanced Analytics in Coral Gables, based his remarks on an analysis of data contained in the 2008-2017 Medical Expenditure Panel Survey (MEPS), a national representative survey sponsored by the Agency for Healthcare Research and Quality. “Between 2013 and 2018 there were six different guidelines released encouraging statin use among ASCVD patients,” he said. “Besides the good number needed to treat, statin use on secondary prevention of CVD is cost effective.”
Given the proven efficacy of statin use in the prevention of CVD, he and his associates set out to examine trends in the proportion of adults with ASCVD using statins and to assess for gender and racial differences in their use. The researchers used ICD-9 and ICD-10 codes to define ASCVD among the MEPS study population, as well as self-reported history of coronary artery disease, peripheral artery disease, and stroke. After excluding adults aged younger than 40 years and those without ASCVD, this left a population of 15,911 patients. Of these, 44% were female, their mean age was 62 years, and 72% were Caucasian.
Overall, statin use increased from 50% in 2008 to 58.7% in 2017, with an average annual percentage change of 0.95% between 2010 and 2017 (P = .01). However, the annual percentage change in statin use was 0.25% among men versus 0.14% among women (P = .022). “Each year during the study period, more than 3 million women with ASCVD were not prescribed a statin, which translated into about 36 million adult-years,” Dr. Salami said. “In 2017, 16% of these women were African Americans and 15% were Hispanic.”
Logistic regression analysis revealed that in 2017, females with ASCVD were less likely to be prescribed a statin, compared with males (odds ratio, 0.52; P less than .001). In addition, compared with whites, blacks were less likely to be prescribed a statin (OR, 0.69; P = .012), as were Hispanics (OR, 0.62; P = .003). “In a multivariate logistic regression controlling for age, health insurance status, and comorbidities, the gender disparity remained statistically significant, but the racial disparity did not,” Dr. Salami said.
In an interview, one of the meeting session’s moderators, Sherry-Ann Brown, MD, PhD, characterized the study’s findings as sobering. “This should be an eye-opener for all of us in medicine, whether we are physicians, pharmacists, nurses, or researchers,” said Dr. Brown, who is a cardiologist and physician scientist at the Mayo Clinic in Rochester, Minn. “We’re all in this together, and we all have a role to play in addressing social determinants of health. I think we need to recognize the fact that we’re not treating blacks, Hispanics, and women to the degree that we should be, compared to whites and men. I think we need to do better, and we need to figure out how to reach that population, and how to improve.”
Dr. Salami acknowledged certain limitations of the study, including the fact that MEPS was carried out in a noninstitutionalized adult population and that the definition of ASCVD was based partly on self-report. “Therefore, an underestimation of number adults with ASCVD is likely,” he said. “We also couldn’t determine adherence to medication nor long-term use of statins among adults with ASCVD.”
He concluded his presentation by noting that, over the 10-year study period, there were about 71.2 million ASCVD adult-years without a statin prescription. “That is a staggering number,” Dr. Salami said.
He reported having no financial disclosures.
SOURCE: Salami A et al. Epi/Lifestyle 2020, Abstract 4.
REPORTING FROM EPI/LIFESTYLE 2020