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The guidelines allow for the addition of short-term clopidogrel to an oral anticoagulant (OAC) in patients with an established OAC indication, such as atrial fibrillation (AF), who undergo transcatheter aortic valve replacement (TAVR). But does the extra antithrombotic protection come with safety issues?

It apparently did in the POPULAR-TAVI trial, which saw an excess of major and minor bleeding in such patients already on an OAC when they underwent TAVR and who then took the antiplatelet agent for the next 3 months.

The patients who instead continued on their OAC as the only post-TAVR antithrombotic, compared with those on double therapy, showed a 37% lower 1-year risk of any bleeding, including major and disabling bleeding.

Importantly, they didn’t seem to pay a price in excess ischemic events, such as stroke or myocardial infarction (MI).

The trial argues against adding clopidogrel on top of OAC in TAVR patients with an OAC indication in order to reduce their risk of bleeding, Jurriën ten Berg, MD, PhD, St. Antonius Hospital, Nieuwegein, the Netherlands, told theheart.org | Medscape Cardiology.

Whether the ischemic event risk was comparable with and without clopidogrel is less clear. “As the study is not powered for the ischemic end points, the answer is less definite. But we did not see a hint of a higher ischemic event rate, especially stroke, in the OAC-alone group,” ten Berg said.

“So we are pretty confident in saying that OAC alone is the optimal treatment.”

The results of POPULAR-TAVI were presented by Vincent Nijenhuis, MD, also from St. Antonius Hospital, on March 29 during the virtual presentation of the American College of Cardiology 2020 Scientific Session/World Congress of Cardiology. Nijenhuis is also first author on the trial’s simultaneous publication in the New England Journal of Medicine.

The only reason to add an antiplatelet in TAVR patients who need to be on an OAC for another indication is to prevent ischemic events like MI, stroke, or death, agreed George D. Dangas, MD, PhD, Mount Sinai Hospital, New York City, for theheart.org | Medscape Cardiology.

But that protection apparently wasn’t needed; for patients on OAC only, “the overall risk–benefit ratio was favorable for them both ways. Although the study is small, I think the findings would be clinically meaningful,” said Dangas, who was not involved in POPULAR-TAVI but was lead author on the GALILEO trial publication.

GALILEO tested a direct oral anticoagulant (DOAC) against dual antiplatelet therapy in patients undergoing TAVR but without a conventional OAC indication. The trial was halted because the DOAC group started to show an excess of bleeding, thromboembolic events, and mortality.

Most POPULAR-TAVI patients were on vitamin K antagonists, but about a quarter were taking DOACs. Clopidogrel was given on an open-label basis.

The trial suggests that, for TAVR patients with an indication for lifelong OAC, “it does appear to be safe to give only an anticoagulant, whether it’s warfarin or a DOAC, and not add clopidogrel,” Robert O. Bonow, MD, Northwestern University, Chicago, told theheart.org | Medscape Cardiology.

“The bottom line appears to be that it’s no worse, and is probably better in terms of bleeding events,” said Bonow, who wasn’t involved in POPULAR-TAVI.

But there are difficulties in interpreting the trial that stem from its design and other issues, he said. For example, it can’t really be concluded that adding an antiplatelet agent to OAC in such patients who undergo TAVR, according to commonly practiced techniques, will increase the risk of bleeding compared with OAC alone.

To begin with, Bonow said, substituting aspirin for clopidogrel might have produced better double-therapy results. But the bigger issues, Bonow said, center on the discretion its operators had in whether to maintain or suspend the patients’ OAC during the TAVR procedure, as well as the unusual bleeding definitions used in the trial.

The first POPULAR-TAVI primary end point was any bleeding that met Valve Academic Research Consortium (VARC) criteria; the second was nonprocedural bleeding that met the Bleeding Academic Research Consortium (BARC) definition.

“Because the VARC-2 classification does not distinguish between procedure-related and nonprocedure-related bleeding events, procedure-related events were defined as BARC type 4 severe bleeding,” the trial’s journal report states. Therefore, “most bleeding at the puncture site was counted as nonprocedure-related.”

It may be Bonow’s biggest issue with the trial, he said. “They’re terming these events that occurred periprocedurally, in the first day or first hours of the procedure, as being ‘nonprocedural’ because they didn’t represent severe BARC bleeding, where you have a subarachnoid hemorrhage or require transfusions.”

An editorial accompanying the trial report also knocks this aspect of the trial design. Although the trial “confirmed” a higher incidence of any bleeding in the double-therapy group, “there are concerns regarding the classification of bleeding and the reliability of secondary outcome analysis,” writes Frederick Feit, MD, NYU Grossman School of Medicine, New York City.

“Bleeding occurring during TAVI or the index hospitalization was unadvisedly defined as non-procedure related, even if it occurred at the access site,” the editorial notes.

Ten Berg noted that procedural bleeding is frequent in TAVI, but the VARC-2 definition doesn’t accommodate them. So “we also used the BARC definition for procedural bleeding, BARC-4,” he told theheart.org | Medscape Cardiology.

“However, BARC-4 describes bleeding during surgery, and it turned out that in POPULAR- TAVI only one patient had BARC-4 bleeding. So we do not at all agree with the editorial.”

Still, the trial’s reported event-rate curves show that “most of the step-up in bleeding, in either arm of the trial, occurred immediately,” Bonow observed. A more consistent, flat trend followed thereafter out to 3 months.

“So half of the bleeding in both arms of the trial occurred at the site of the arterial puncture. Though it wasn’t considered severe, it was indeed periprocedural,” Bonow said, interpreting the results.

The POPULAR-TAVI journal report says the procedures were performed according to local site protocols, and site physicians were allowed to decide whether to continue or suspend OAC. But “the trial protocol advised physicians to continue oral anticoagulation during admission for the TAVI procedure.”

Many of the patients, regardless of randomization group, “went through the procedure under full anticoagulation,” Dangas agreed. POPULAR-TAVI, it seems, “is the first anticoagulation study ever to start anticoagulation before the procedure.”

Bleeding event rates in the trial “are somewhat high because of this unusual procedural feature of the study,” Dangas said.

“It’s therefore not surprising that so much of the bleeding occurred in the first hours of the procedure itself,” observed Bonow.

The trial enrolled 313 patients in four European countries who were on OAC for an approved indication, predominantly AF, and underwent TAVR. Their mean age was about 81 years, and 45.4% were women. They were randomly assigned to receive or not receive clopidogrel in a loading dose, followed by 75 mg/d on top of their OAC for 3 months, and were followed out to a year.

All bleeding that met VARC-2 criteria, the first primary end point, occurred in 21.7% of the 157 patients on OAC alone and 34.6% of the 156 who received double therapy (risk ratio [RR], 0.63; 95% CI, 0.43 - 0.90; P = .011).

The second primary end point, “nonprocedural” bleeding that met BARC-4 criteria, occurred in 21.7% and 34.0%, respectively, of patients (RR, 0.64; 95% CI, 0.44 - 0.92; P = .015).

There were also two secondary composite outcomes. The first consisted of nonprocedural bleeding, cardiovascular (CV) death, any stroke, and MI, and was seen in 31.2% of patients on OAC alone and 45.5% of those on OAC plus clopidogrel (RR, 0.69; 95% CI, 0.51 - 0.92), an absolute difference that was within the prospectively defined noninferiority margins.

The other secondary end point — CV death, ischemic stroke, and MI — occurred in 13.4% of those receiving only OAC and 17.3% on added clopidogrel (RR, 0.77; 95% CI, 0.46 - 1.31), which was nonsignificant for superiority.

“Could they have done better by holding the anticoagulation, whether warfarin or a DOAC, during that time? That’s what I think many centers might do if they’re performing a TAVR,” Bonow said.

“It seems to me that could have been done in this trial as well: they could have stopped the anticoagulation, done the procedure, and started the anticoagulation after, the way you would normally in a patient getting a TAVR.”

Such a practice might have reduced the risk of procedural bleeding as it is usually defined in TAVR in both groups, thereby potentially blunting any difference in bleeding rate between the two groups.

“That’s my take on it.” Still, he said, the trial’s message remains: OAC without clopidogrel is safe in POPULAR-TAVI-like patients.

Nijenhuis had no disclosures. Ten Berg disclosed no industry ties. Disclosures for the other authors are in the report. Bonow has previously reported no disclosures. Dangas has previously disclosed receiving grants and fees from Bayer, fees from Janssen; grants and personal fees from Daiichi-Sankyo; and other compensation from Medtronic. Feit discloses personal fees from Abbott Vascular and other relationships with Medtronic, Boston Scientific, and Sapheon.

This article first appeared on Medscape.com.

The guidelines allow for the addition of short-term clopidogrel to an oral anticoagulant (OAC) in patients with an established OAC indication, such as atrial fibrillation (AF), who undergo transcatheter aortic valve replacement (TAVR). But does the extra antithrombotic protection come with safety issues?

It apparently did in the POPULAR-TAVI trial, which saw an excess of major and minor bleeding in such patients already on an OAC when they underwent TAVR and who then took the antiplatelet agent for the next 3 months.

The patients who instead continued on their OAC as the only post-TAVR antithrombotic, compared with those on double therapy, showed a 37% lower 1-year risk of any bleeding, including major and disabling bleeding.

Importantly, they didn’t seem to pay a price in excess ischemic events, such as stroke or myocardial infarction (MI).

The trial argues against adding clopidogrel on top of OAC in TAVR patients with an OAC indication in order to reduce their risk of bleeding, Jurriën ten Berg, MD, PhD, St. Antonius Hospital, Nieuwegein, the Netherlands, told theheart.org | Medscape Cardiology.

Whether the ischemic event risk was comparable with and without clopidogrel is less clear. “As the study is not powered for the ischemic end points, the answer is less definite. But we did not see a hint of a higher ischemic event rate, especially stroke, in the OAC-alone group,” ten Berg said.

“So we are pretty confident in saying that OAC alone is the optimal treatment.”

The results of POPULAR-TAVI were presented by Vincent Nijenhuis, MD, also from St. Antonius Hospital, on March 29 during the virtual presentation of the American College of Cardiology 2020 Scientific Session/World Congress of Cardiology. Nijenhuis is also first author on the trial’s simultaneous publication in the New England Journal of Medicine.

The only reason to add an antiplatelet in TAVR patients who need to be on an OAC for another indication is to prevent ischemic events like MI, stroke, or death, agreed George D. Dangas, MD, PhD, Mount Sinai Hospital, New York City, for theheart.org | Medscape Cardiology.

But that protection apparently wasn’t needed; for patients on OAC only, “the overall risk–benefit ratio was favorable for them both ways. Although the study is small, I think the findings would be clinically meaningful,” said Dangas, who was not involved in POPULAR-TAVI but was lead author on the GALILEO trial publication.

GALILEO tested a direct oral anticoagulant (DOAC) against dual antiplatelet therapy in patients undergoing TAVR but without a conventional OAC indication. The trial was halted because the DOAC group started to show an excess of bleeding, thromboembolic events, and mortality.

Most POPULAR-TAVI patients were on vitamin K antagonists, but about a quarter were taking DOACs. Clopidogrel was given on an open-label basis.

The trial suggests that, for TAVR patients with an indication for lifelong OAC, “it does appear to be safe to give only an anticoagulant, whether it’s warfarin or a DOAC, and not add clopidogrel,” Robert O. Bonow, MD, Northwestern University, Chicago, told theheart.org | Medscape Cardiology.

“The bottom line appears to be that it’s no worse, and is probably better in terms of bleeding events,” said Bonow, who wasn’t involved in POPULAR-TAVI.

But there are difficulties in interpreting the trial that stem from its design and other issues, he said. For example, it can’t really be concluded that adding an antiplatelet agent to OAC in such patients who undergo TAVR, according to commonly practiced techniques, will increase the risk of bleeding compared with OAC alone.

To begin with, Bonow said, substituting aspirin for clopidogrel might have produced better double-therapy results. But the bigger issues, Bonow said, center on the discretion its operators had in whether to maintain or suspend the patients’ OAC during the TAVR procedure, as well as the unusual bleeding definitions used in the trial.

The first POPULAR-TAVI primary end point was any bleeding that met Valve Academic Research Consortium (VARC) criteria; the second was nonprocedural bleeding that met the Bleeding Academic Research Consortium (BARC) definition.

“Because the VARC-2 classification does not distinguish between procedure-related and nonprocedure-related bleeding events, procedure-related events were defined as BARC type 4 severe bleeding,” the trial’s journal report states. Therefore, “most bleeding at the puncture site was counted as nonprocedure-related.”

It may be Bonow’s biggest issue with the trial, he said. “They’re terming these events that occurred periprocedurally, in the first day or first hours of the procedure, as being ‘nonprocedural’ because they didn’t represent severe BARC bleeding, where you have a subarachnoid hemorrhage or require transfusions.”

An editorial accompanying the trial report also knocks this aspect of the trial design. Although the trial “confirmed” a higher incidence of any bleeding in the double-therapy group, “there are concerns regarding the classification of bleeding and the reliability of secondary outcome analysis,” writes Frederick Feit, MD, NYU Grossman School of Medicine, New York City.

“Bleeding occurring during TAVI or the index hospitalization was unadvisedly defined as non-procedure related, even if it occurred at the access site,” the editorial notes.

Ten Berg noted that procedural bleeding is frequent in TAVI, but the VARC-2 definition doesn’t accommodate them. So “we also used the BARC definition for procedural bleeding, BARC-4,” he told theheart.org | Medscape Cardiology.

“However, BARC-4 describes bleeding during surgery, and it turned out that in POPULAR- TAVI only one patient had BARC-4 bleeding. So we do not at all agree with the editorial.”

Still, the trial’s reported event-rate curves show that “most of the step-up in bleeding, in either arm of the trial, occurred immediately,” Bonow observed. A more consistent, flat trend followed thereafter out to 3 months.

“So half of the bleeding in both arms of the trial occurred at the site of the arterial puncture. Though it wasn’t considered severe, it was indeed periprocedural,” Bonow said, interpreting the results.

The POPULAR-TAVI journal report says the procedures were performed according to local site protocols, and site physicians were allowed to decide whether to continue or suspend OAC. But “the trial protocol advised physicians to continue oral anticoagulation during admission for the TAVI procedure.”

Many of the patients, regardless of randomization group, “went through the procedure under full anticoagulation,” Dangas agreed. POPULAR-TAVI, it seems, “is the first anticoagulation study ever to start anticoagulation before the procedure.”

Bleeding event rates in the trial “are somewhat high because of this unusual procedural feature of the study,” Dangas said.

“It’s therefore not surprising that so much of the bleeding occurred in the first hours of the procedure itself,” observed Bonow.

The trial enrolled 313 patients in four European countries who were on OAC for an approved indication, predominantly AF, and underwent TAVR. Their mean age was about 81 years, and 45.4% were women. They were randomly assigned to receive or not receive clopidogrel in a loading dose, followed by 75 mg/d on top of their OAC for 3 months, and were followed out to a year.

All bleeding that met VARC-2 criteria, the first primary end point, occurred in 21.7% of the 157 patients on OAC alone and 34.6% of the 156 who received double therapy (risk ratio [RR], 0.63; 95% CI, 0.43 - 0.90; P = .011).

The second primary end point, “nonprocedural” bleeding that met BARC-4 criteria, occurred in 21.7% and 34.0%, respectively, of patients (RR, 0.64; 95% CI, 0.44 - 0.92; P = .015).

There were also two secondary composite outcomes. The first consisted of nonprocedural bleeding, cardiovascular (CV) death, any stroke, and MI, and was seen in 31.2% of patients on OAC alone and 45.5% of those on OAC plus clopidogrel (RR, 0.69; 95% CI, 0.51 - 0.92), an absolute difference that was within the prospectively defined noninferiority margins.

The other secondary end point — CV death, ischemic stroke, and MI — occurred in 13.4% of those receiving only OAC and 17.3% on added clopidogrel (RR, 0.77; 95% CI, 0.46 - 1.31), which was nonsignificant for superiority.

“Could they have done better by holding the anticoagulation, whether warfarin or a DOAC, during that time? That’s what I think many centers might do if they’re performing a TAVR,” Bonow said.

“It seems to me that could have been done in this trial as well: they could have stopped the anticoagulation, done the procedure, and started the anticoagulation after, the way you would normally in a patient getting a TAVR.”

Such a practice might have reduced the risk of procedural bleeding as it is usually defined in TAVR in both groups, thereby potentially blunting any difference in bleeding rate between the two groups.

“That’s my take on it.” Still, he said, the trial’s message remains: OAC without clopidogrel is safe in POPULAR-TAVI-like patients.

Nijenhuis had no disclosures. Ten Berg disclosed no industry ties. Disclosures for the other authors are in the report. Bonow has previously reported no disclosures. Dangas has previously disclosed receiving grants and fees from Bayer, fees from Janssen; grants and personal fees from Daiichi-Sankyo; and other compensation from Medtronic. Feit discloses personal fees from Abbott Vascular and other relationships with Medtronic, Boston Scientific, and Sapheon.

This article first appeared on Medscape.com.

The guidelines allow for the addition of short-term clopidogrel to an oral anticoagulant (OAC) in patients with an established OAC indication, such as atrial fibrillation (AF), who undergo transcatheter aortic valve replacement (TAVR). But does the extra antithrombotic protection come with safety issues?

It apparently did in the POPULAR-TAVI trial, which saw an excess of major and minor bleeding in such patients already on an OAC when they underwent TAVR and who then took the antiplatelet agent for the next 3 months.

The patients who instead continued on their OAC as the only post-TAVR antithrombotic, compared with those on double therapy, showed a 37% lower 1-year risk of any bleeding, including major and disabling bleeding.

Importantly, they didn’t seem to pay a price in excess ischemic events, such as stroke or myocardial infarction (MI).

The trial argues against adding clopidogrel on top of OAC in TAVR patients with an OAC indication in order to reduce their risk of bleeding, Jurriën ten Berg, MD, PhD, St. Antonius Hospital, Nieuwegein, the Netherlands, told theheart.org | Medscape Cardiology.

Whether the ischemic event risk was comparable with and without clopidogrel is less clear. “As the study is not powered for the ischemic end points, the answer is less definite. But we did not see a hint of a higher ischemic event rate, especially stroke, in the OAC-alone group,” ten Berg said.

“So we are pretty confident in saying that OAC alone is the optimal treatment.”

The results of POPULAR-TAVI were presented by Vincent Nijenhuis, MD, also from St. Antonius Hospital, on March 29 during the virtual presentation of the American College of Cardiology 2020 Scientific Session/World Congress of Cardiology. Nijenhuis is also first author on the trial’s simultaneous publication in the New England Journal of Medicine.

The only reason to add an antiplatelet in TAVR patients who need to be on an OAC for another indication is to prevent ischemic events like MI, stroke, or death, agreed George D. Dangas, MD, PhD, Mount Sinai Hospital, New York City, for theheart.org | Medscape Cardiology.

But that protection apparently wasn’t needed; for patients on OAC only, “the overall risk–benefit ratio was favorable for them both ways. Although the study is small, I think the findings would be clinically meaningful,” said Dangas, who was not involved in POPULAR-TAVI but was lead author on the GALILEO trial publication.

GALILEO tested a direct oral anticoagulant (DOAC) against dual antiplatelet therapy in patients undergoing TAVR but without a conventional OAC indication. The trial was halted because the DOAC group started to show an excess of bleeding, thromboembolic events, and mortality.

Most POPULAR-TAVI patients were on vitamin K antagonists, but about a quarter were taking DOACs. Clopidogrel was given on an open-label basis.

The trial suggests that, for TAVR patients with an indication for lifelong OAC, “it does appear to be safe to give only an anticoagulant, whether it’s warfarin or a DOAC, and not add clopidogrel,” Robert O. Bonow, MD, Northwestern University, Chicago, told theheart.org | Medscape Cardiology.

“The bottom line appears to be that it’s no worse, and is probably better in terms of bleeding events,” said Bonow, who wasn’t involved in POPULAR-TAVI.

But there are difficulties in interpreting the trial that stem from its design and other issues, he said. For example, it can’t really be concluded that adding an antiplatelet agent to OAC in such patients who undergo TAVR, according to commonly practiced techniques, will increase the risk of bleeding compared with OAC alone.

To begin with, Bonow said, substituting aspirin for clopidogrel might have produced better double-therapy results. But the bigger issues, Bonow said, center on the discretion its operators had in whether to maintain or suspend the patients’ OAC during the TAVR procedure, as well as the unusual bleeding definitions used in the trial.

The first POPULAR-TAVI primary end point was any bleeding that met Valve Academic Research Consortium (VARC) criteria; the second was nonprocedural bleeding that met the Bleeding Academic Research Consortium (BARC) definition.

“Because the VARC-2 classification does not distinguish between procedure-related and nonprocedure-related bleeding events, procedure-related events were defined as BARC type 4 severe bleeding,” the trial’s journal report states. Therefore, “most bleeding at the puncture site was counted as nonprocedure-related.”

It may be Bonow’s biggest issue with the trial, he said. “They’re terming these events that occurred periprocedurally, in the first day or first hours of the procedure, as being ‘nonprocedural’ because they didn’t represent severe BARC bleeding, where you have a subarachnoid hemorrhage or require transfusions.”

An editorial accompanying the trial report also knocks this aspect of the trial design. Although the trial “confirmed” a higher incidence of any bleeding in the double-therapy group, “there are concerns regarding the classification of bleeding and the reliability of secondary outcome analysis,” writes Frederick Feit, MD, NYU Grossman School of Medicine, New York City.

“Bleeding occurring during TAVI or the index hospitalization was unadvisedly defined as non-procedure related, even if it occurred at the access site,” the editorial notes.

Ten Berg noted that procedural bleeding is frequent in TAVI, but the VARC-2 definition doesn’t accommodate them. So “we also used the BARC definition for procedural bleeding, BARC-4,” he told theheart.org | Medscape Cardiology.

“However, BARC-4 describes bleeding during surgery, and it turned out that in POPULAR- TAVI only one patient had BARC-4 bleeding. So we do not at all agree with the editorial.”

Still, the trial’s reported event-rate curves show that “most of the step-up in bleeding, in either arm of the trial, occurred immediately,” Bonow observed. A more consistent, flat trend followed thereafter out to 3 months.

“So half of the bleeding in both arms of the trial occurred at the site of the arterial puncture. Though it wasn’t considered severe, it was indeed periprocedural,” Bonow said, interpreting the results.

The POPULAR-TAVI journal report says the procedures were performed according to local site protocols, and site physicians were allowed to decide whether to continue or suspend OAC. But “the trial protocol advised physicians to continue oral anticoagulation during admission for the TAVI procedure.”

Many of the patients, regardless of randomization group, “went through the procedure under full anticoagulation,” Dangas agreed. POPULAR-TAVI, it seems, “is the first anticoagulation study ever to start anticoagulation before the procedure.”

Bleeding event rates in the trial “are somewhat high because of this unusual procedural feature of the study,” Dangas said.

“It’s therefore not surprising that so much of the bleeding occurred in the first hours of the procedure itself,” observed Bonow.

The trial enrolled 313 patients in four European countries who were on OAC for an approved indication, predominantly AF, and underwent TAVR. Their mean age was about 81 years, and 45.4% were women. They were randomly assigned to receive or not receive clopidogrel in a loading dose, followed by 75 mg/d on top of their OAC for 3 months, and were followed out to a year.

All bleeding that met VARC-2 criteria, the first primary end point, occurred in 21.7% of the 157 patients on OAC alone and 34.6% of the 156 who received double therapy (risk ratio [RR], 0.63; 95% CI, 0.43 - 0.90; P = .011).

The second primary end point, “nonprocedural” bleeding that met BARC-4 criteria, occurred in 21.7% and 34.0%, respectively, of patients (RR, 0.64; 95% CI, 0.44 - 0.92; P = .015).

There were also two secondary composite outcomes. The first consisted of nonprocedural bleeding, cardiovascular (CV) death, any stroke, and MI, and was seen in 31.2% of patients on OAC alone and 45.5% of those on OAC plus clopidogrel (RR, 0.69; 95% CI, 0.51 - 0.92), an absolute difference that was within the prospectively defined noninferiority margins.

The other secondary end point — CV death, ischemic stroke, and MI — occurred in 13.4% of those receiving only OAC and 17.3% on added clopidogrel (RR, 0.77; 95% CI, 0.46 - 1.31), which was nonsignificant for superiority.

“Could they have done better by holding the anticoagulation, whether warfarin or a DOAC, during that time? That’s what I think many centers might do if they’re performing a TAVR,” Bonow said.

“It seems to me that could have been done in this trial as well: they could have stopped the anticoagulation, done the procedure, and started the anticoagulation after, the way you would normally in a patient getting a TAVR.”

Such a practice might have reduced the risk of procedural bleeding as it is usually defined in TAVR in both groups, thereby potentially blunting any difference in bleeding rate between the two groups.

“That’s my take on it.” Still, he said, the trial’s message remains: OAC without clopidogrel is safe in POPULAR-TAVI-like patients.

Nijenhuis had no disclosures. Ten Berg disclosed no industry ties. Disclosures for the other authors are in the report. Bonow has previously reported no disclosures. Dangas has previously disclosed receiving grants and fees from Bayer, fees from Janssen; grants and personal fees from Daiichi-Sankyo; and other compensation from Medtronic. Feit discloses personal fees from Abbott Vascular and other relationships with Medtronic, Boston Scientific, and Sapheon.

This article first appeared on Medscape.com.

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.

mzoler@mdedge.com

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.

mzoler@mdedge.com

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.

mzoler@mdedge.com

SOURCE: Raal F. ACC 20. Abstract 411-12.

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.

bjancin@mdedge.com

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.

bjancin@mdedge.com

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.

bjancin@mdedge.com

Infants who are hospitalized for severe bronchiolitis and receive acid-suppressant medications may be at risk of developing allergic disease by age 3 years, according to recent research released as an abstract for the American Academy of Allergy, Asthma & Immunology (AAAAI) Annual Meeting.

The AAAAI canceled their annual meeting and provided abstracts and access to presenters for press coverage

“Among children with a history of severe bronchiolitis during infancy, exposure to acid-suppressant medications during infancy further increases the risk of developing recurrent wheeze by age 3 years,” Lacey B. Robinson, MD, of the division of rheumatology, allergy, and immunology in the department of medicine at Massachusetts General Hospital in Boston, said in an interview.

Bronchiolitis is a risk factor in infants for developing conditions such as recurrent wheeze and childhood asthma in early childhood. Acid-suppressant medications like proton pump inhibitors (PPIs) and histamine-2 receptor antagonists (H2RAs) may further increase the risk of allergic disease. One study by Mitre et al. published in JAMA Pediatrics showed use of acid-suppressant medications in infants up to 6 months raised the risk of allergic disease (JAMA Pediatr. 2018;172[6]:e180315). Some studies suggest between 30% and 50% of infants diagnosed with bronchiolitis requiring hospitalization will develop asthma by age 5 years (J Allergy Clin Immunol Pract. 2017 Jan - Feb;5[1]:92-6).

“Children with severe bronchiolitis during infancy are at a high risk of developing recurrent wheeze and subsequent asthma. There is limited evidence to suggest that exposure to acid suppressant medications [such as proton pump inhibitors and histamine-2 receptor antagonists] prenatally and during early childhood increases the risk of childhood asthma,” Dr. Robinson said. “It is not known if exposure to acid suppressant medications during infancy further increases the risk of developing recurrent wheeze among high-risk children, such as in those with a history of severe bronchiolitis during infancy.”

Dr. Robinson and colleagues performed a multicenter, prospective cohort study of 921 infants who were hospitalized for severe bronchiolitis between 2011 and 2014. The investigators reviewed the medical records of the infants for acid suppressant medication use, as well as parent report of acid suppressant medication use, during an infant’s first 12 months. Overall, 879 children were analyzed after excluding for patients who developed recurrent wheeze prior to receiving acid suppressant medications, as well as patients with incomplete data. The investigators used the National Institutes of Health Guidelines for the Diagnosis and Management of Asthma (EPR-3) to define recurrent wheeze. A Cox-proportional hazard model was used to analyze the time to event, which was stratified by age and adjusted for confounders.

Infants with a history of severe bronchiolitis were at greater risk of developing recurrent wheeze by age 3 years after being exposed to acid-suppressant medications, compared with infants who were not exposed, Dr. Robinson said. Of the 879 infants in the final analysis, 159 (18%) received acid-suppressant medications, and 68 of 159 patients (43%) went on to develop recurrent wheeze, compared with 206 of 720 infants (29%) who were not exposed (unadjusted hazard ratio, 1.63; 95% confidence interval, 1.24-2.14).

After adjustment for confounders such as gender, race and ethnicity; gestational age; delivery type; severity of bronchiolitis; respiratory syncytial virus (RSV) infection status; maternal atopy; use of acid-suppressant medications during pregnancy; median household income; and insurance status, the association between recurrent wheeze and acid-suppressant medication use during infancy remained (adjusted HR, 1.54; 95% CI, 1.15-2.07).

“More research is needed on this important topic including studies in other populations,” such as in healthy children, Dr. Robinson said. “We encourage future research on this important and understudied topic, including further research on the potential underlying mechanisms of this association.”

Dr. Robinson reported no relevant financial disclosures.

SOURCE: Robinson L. AAAAI 2020, Abstract L1

Infants who are hospitalized for severe bronchiolitis and receive acid-suppressant medications may be at risk of developing allergic disease by age 3 years, according to recent research released as an abstract for the American Academy of Allergy, Asthma & Immunology (AAAAI) Annual Meeting.

The AAAAI canceled their annual meeting and provided abstracts and access to presenters for press coverage

“Among children with a history of severe bronchiolitis during infancy, exposure to acid-suppressant medications during infancy further increases the risk of developing recurrent wheeze by age 3 years,” Lacey B. Robinson, MD, of the division of rheumatology, allergy, and immunology in the department of medicine at Massachusetts General Hospital in Boston, said in an interview.

Bronchiolitis is a risk factor in infants for developing conditions such as recurrent wheeze and childhood asthma in early childhood. Acid-suppressant medications like proton pump inhibitors (PPIs) and histamine-2 receptor antagonists (H2RAs) may further increase the risk of allergic disease. One study by Mitre et al. published in JAMA Pediatrics showed use of acid-suppressant medications in infants up to 6 months raised the risk of allergic disease (JAMA Pediatr. 2018;172[6]:e180315). Some studies suggest between 30% and 50% of infants diagnosed with bronchiolitis requiring hospitalization will develop asthma by age 5 years (J Allergy Clin Immunol Pract. 2017 Jan - Feb;5[1]:92-6).

“Children with severe bronchiolitis during infancy are at a high risk of developing recurrent wheeze and subsequent asthma. There is limited evidence to suggest that exposure to acid suppressant medications [such as proton pump inhibitors and histamine-2 receptor antagonists] prenatally and during early childhood increases the risk of childhood asthma,” Dr. Robinson said. “It is not known if exposure to acid suppressant medications during infancy further increases the risk of developing recurrent wheeze among high-risk children, such as in those with a history of severe bronchiolitis during infancy.”

Dr. Robinson and colleagues performed a multicenter, prospective cohort study of 921 infants who were hospitalized for severe bronchiolitis between 2011 and 2014. The investigators reviewed the medical records of the infants for acid suppressant medication use, as well as parent report of acid suppressant medication use, during an infant’s first 12 months. Overall, 879 children were analyzed after excluding for patients who developed recurrent wheeze prior to receiving acid suppressant medications, as well as patients with incomplete data. The investigators used the National Institutes of Health Guidelines for the Diagnosis and Management of Asthma (EPR-3) to define recurrent wheeze. A Cox-proportional hazard model was used to analyze the time to event, which was stratified by age and adjusted for confounders.

Infants with a history of severe bronchiolitis were at greater risk of developing recurrent wheeze by age 3 years after being exposed to acid-suppressant medications, compared with infants who were not exposed, Dr. Robinson said. Of the 879 infants in the final analysis, 159 (18%) received acid-suppressant medications, and 68 of 159 patients (43%) went on to develop recurrent wheeze, compared with 206 of 720 infants (29%) who were not exposed (unadjusted hazard ratio, 1.63; 95% confidence interval, 1.24-2.14).

After adjustment for confounders such as gender, race and ethnicity; gestational age; delivery type; severity of bronchiolitis; respiratory syncytial virus (RSV) infection status; maternal atopy; use of acid-suppressant medications during pregnancy; median household income; and insurance status, the association between recurrent wheeze and acid-suppressant medication use during infancy remained (adjusted HR, 1.54; 95% CI, 1.15-2.07).

“More research is needed on this important topic including studies in other populations,” such as in healthy children, Dr. Robinson said. “We encourage future research on this important and understudied topic, including further research on the potential underlying mechanisms of this association.”

Dr. Robinson reported no relevant financial disclosures.

SOURCE: Robinson L. AAAAI 2020, Abstract L1

Infants who are hospitalized for severe bronchiolitis and receive acid-suppressant medications may be at risk of developing allergic disease by age 3 years, according to recent research released as an abstract for the American Academy of Allergy, Asthma & Immunology (AAAAI) Annual Meeting.

The AAAAI canceled their annual meeting and provided abstracts and access to presenters for press coverage

“Among children with a history of severe bronchiolitis during infancy, exposure to acid-suppressant medications during infancy further increases the risk of developing recurrent wheeze by age 3 years,” Lacey B. Robinson, MD, of the division of rheumatology, allergy, and immunology in the department of medicine at Massachusetts General Hospital in Boston, said in an interview.

Bronchiolitis is a risk factor in infants for developing conditions such as recurrent wheeze and childhood asthma in early childhood. Acid-suppressant medications like proton pump inhibitors (PPIs) and histamine-2 receptor antagonists (H2RAs) may further increase the risk of allergic disease. One study by Mitre et al. published in JAMA Pediatrics showed use of acid-suppressant medications in infants up to 6 months raised the risk of allergic disease (JAMA Pediatr. 2018;172[6]:e180315). Some studies suggest between 30% and 50% of infants diagnosed with bronchiolitis requiring hospitalization will develop asthma by age 5 years (J Allergy Clin Immunol Pract. 2017 Jan - Feb;5[1]:92-6).

“Children with severe bronchiolitis during infancy are at a high risk of developing recurrent wheeze and subsequent asthma. There is limited evidence to suggest that exposure to acid suppressant medications [such as proton pump inhibitors and histamine-2 receptor antagonists] prenatally and during early childhood increases the risk of childhood asthma,” Dr. Robinson said. “It is not known if exposure to acid suppressant medications during infancy further increases the risk of developing recurrent wheeze among high-risk children, such as in those with a history of severe bronchiolitis during infancy.”

Dr. Robinson and colleagues performed a multicenter, prospective cohort study of 921 infants who were hospitalized for severe bronchiolitis between 2011 and 2014. The investigators reviewed the medical records of the infants for acid suppressant medication use, as well as parent report of acid suppressant medication use, during an infant’s first 12 months. Overall, 879 children were analyzed after excluding for patients who developed recurrent wheeze prior to receiving acid suppressant medications, as well as patients with incomplete data. The investigators used the National Institutes of Health Guidelines for the Diagnosis and Management of Asthma (EPR-3) to define recurrent wheeze. A Cox-proportional hazard model was used to analyze the time to event, which was stratified by age and adjusted for confounders.

Infants with a history of severe bronchiolitis were at greater risk of developing recurrent wheeze by age 3 years after being exposed to acid-suppressant medications, compared with infants who were not exposed, Dr. Robinson said. Of the 879 infants in the final analysis, 159 (18%) received acid-suppressant medications, and 68 of 159 patients (43%) went on to develop recurrent wheeze, compared with 206 of 720 infants (29%) who were not exposed (unadjusted hazard ratio, 1.63; 95% confidence interval, 1.24-2.14).

After adjustment for confounders such as gender, race and ethnicity; gestational age; delivery type; severity of bronchiolitis; respiratory syncytial virus (RSV) infection status; maternal atopy; use of acid-suppressant medications during pregnancy; median household income; and insurance status, the association between recurrent wheeze and acid-suppressant medication use during infancy remained (adjusted HR, 1.54; 95% CI, 1.15-2.07).

“More research is needed on this important topic including studies in other populations,” such as in healthy children, Dr. Robinson said. “We encourage future research on this important and understudied topic, including further research on the potential underlying mechanisms of this association.”

Dr. Robinson reported no relevant financial disclosures.

SOURCE: Robinson L. AAAAI 2020, Abstract L1

For patients with lupus nephritis, kidney response improves when voclosporin (Aurinia Pharmaceuticals) is added to mycophenolate and low-dose corticosteroids, results from the phase 3 AURORA trial show.
 

The calcineurin inhibitor is the first novel agent to demonstrate effectiveness in the treatment of people with lupus nephritis, a disease that can lead to irreversible kidney damage, kidney failure, and even death.

“We believe that voclosporin – as an add-on therapy – will help more patients achieve remission,” said Keisha Gibson, MD, MPH, chief of pediatric nephrology at the UNC Kidney Center in Chapel Hill, North Carolina, who led the study and presented the findings during a virtual session at the National Kidney Foundation 2020 Spring Clinical Meetings.

The burden that lupus places on patients and the health system is high, she reported. Patients with lupus and uncontrolled kidney disease frequently have complications that require hospitalization, can suffer complete or partial loss of income, and can become temporarily disabled. And up to 50% of lupus patients will develop lupus nephritis.

“When we are lucky and see early treatment responses in our patients, we know that their long-term outcomes, measured by proteinuria reduction, are quite good,” said Gibson. “Unfortunately, in 10% to 30% of patients, despite standard-of-care therapies, we see progression to end-stage kidney disease within 15 years of diagnosis. This confers a huge cost to overall health and quality of life, and is an excess burden to the healthcare system.

“It is clear that one of the biggest risk factors for these patients who have kidney disease that is progressing to kidney failure is an inability to control the inflammation and chronic damage from uncontrolled disease,” she told Medscape Medical News.

“While there have certainly been a few advances in the care of patients with lupus disease, I believe that this therapy may help move the needle, specifically for patients with kidney involvement from their lupus disease,” she added.

Renal Response Much Higher With Voclosporin

The typical standard of care for patients with active lupus and kidney disease is either a combination of cyclophosphamide plus steroids or a combination of mycophenolate mofetil plus steroids.

The global, double-blind, randomized, placebo-controlled trial compared the effectiveness and safety of twice-daily oral voclosporin 23.7 mg with placebo. All 357 study participants also received mycophenolate 2 g daily and rapidly tapered low-dose oral corticosteroids.

At 1 year, the renal response rate was higher in the voclosporin group than in the placebo group (40.8% vs 22.5%; odds ratio, 2.65; P < .001).

“AURORA patients achieved low levels of protein twice as quickly as patients on standard of care,” the researchers write in their abstract. Median time to the achievement of a urine protein to creatinine ratio below 0.5 mg/mg was significantly and clinically better with voclosporin than with placebo (169 vs 372 days; log rank P < .001).

And voclosporin was well tolerated. The percentage of serious adverse events was similar in the voclosporin and placebo groups (20.8% vs 21.3%), with infection being the most common serious event (10.1% vs 11.2%).

In the voclosporin group, there were no significant differences between baseline and 1 year estimated glomerular filtration rates (eGFR), blood pressure, lipid levels, or sugar levels.

And there were fewer deaths in the voclosporin group than in the placebo group (1 vs 5).

Benefits were seen in all subgroups, including age, sex, race, biopsy class, geographic region of origin, and mycophenolate exposure at screening, Gibson reported.

Promise of a New Treatment

The promise of a new treatment is exciting for the field, said Joseph Vassalotti, MD, chief medical officer of the National Kidney Foundation.

However, it’s important to note that “this study is applicable only to patients with lupus nephritis with preserved kidney function,” he added.

An “eGFR less than 45 mL/min per 1.73 m² was implied as an exclusion criteria, so I would say it certainly doesn’t apply to patients with impaired kidney function,” he said, pointing out that this will be clearer when the final data are published.

The study cohort was heterogeneous; 86% of participants had class 3 or 4 biopsy findings and 14% had class 5, so the superiority of voclosporin is convincing, he said.

“We look forward to full publication and more details,” he told Medscape Medical News. “They do have an extension study, and it will be interesting to see how that plays out.”

Voclosporin was granted Fast Track designation by the US Food and Drug Administration in 2016, and these positive phase 3 results mean that a New Drug Application will likely be filed in the next few months. If approved, the drug could be on the market by 2021, according to a press release from Aurinia.

Nephrologists are familiar with calcineurin inhibitors, so it will be interesting to see, given the success of this trial, if voclosporin has a potential role in other kidney diseases, “such as minimal change disease,” said Vassalotti.

He added that there are concerns, unrelated to the AURORA trial, about the supply of hydroxychloroquine, which is also used for the treatment of lupus nephritis. “An overarching concern is that the supply will be limited now that the drug is being studied and used as prophylaxis after exposure to SARS-CoV-2 and as a treatment for COVID-19, creating challenges for patients with lupus nephritis trying to obtain their needed medication,” he said.

Gibson reports no relevant financial relationships. Two coauthors work for the drugmaker, Aurinia. Vassalotti reports no relevant financial relationships.
 

This article first appeared on Medscape.com.

For patients with lupus nephritis, kidney response improves when voclosporin (Aurinia Pharmaceuticals) is added to mycophenolate and low-dose corticosteroids, results from the phase 3 AURORA trial show.
 

The calcineurin inhibitor is the first novel agent to demonstrate effectiveness in the treatment of people with lupus nephritis, a disease that can lead to irreversible kidney damage, kidney failure, and even death.

“We believe that voclosporin – as an add-on therapy – will help more patients achieve remission,” said Keisha Gibson, MD, MPH, chief of pediatric nephrology at the UNC Kidney Center in Chapel Hill, North Carolina, who led the study and presented the findings during a virtual session at the National Kidney Foundation 2020 Spring Clinical Meetings.

The burden that lupus places on patients and the health system is high, she reported. Patients with lupus and uncontrolled kidney disease frequently have complications that require hospitalization, can suffer complete or partial loss of income, and can become temporarily disabled. And up to 50% of lupus patients will develop lupus nephritis.

“When we are lucky and see early treatment responses in our patients, we know that their long-term outcomes, measured by proteinuria reduction, are quite good,” said Gibson. “Unfortunately, in 10% to 30% of patients, despite standard-of-care therapies, we see progression to end-stage kidney disease within 15 years of diagnosis. This confers a huge cost to overall health and quality of life, and is an excess burden to the healthcare system.

“It is clear that one of the biggest risk factors for these patients who have kidney disease that is progressing to kidney failure is an inability to control the inflammation and chronic damage from uncontrolled disease,” she told Medscape Medical News.

“While there have certainly been a few advances in the care of patients with lupus disease, I believe that this therapy may help move the needle, specifically for patients with kidney involvement from their lupus disease,” she added.

Renal Response Much Higher With Voclosporin

The typical standard of care for patients with active lupus and kidney disease is either a combination of cyclophosphamide plus steroids or a combination of mycophenolate mofetil plus steroids.

The global, double-blind, randomized, placebo-controlled trial compared the effectiveness and safety of twice-daily oral voclosporin 23.7 mg with placebo. All 357 study participants also received mycophenolate 2 g daily and rapidly tapered low-dose oral corticosteroids.

At 1 year, the renal response rate was higher in the voclosporin group than in the placebo group (40.8% vs 22.5%; odds ratio, 2.65; P < .001).

“AURORA patients achieved low levels of protein twice as quickly as patients on standard of care,” the researchers write in their abstract. Median time to the achievement of a urine protein to creatinine ratio below 0.5 mg/mg was significantly and clinically better with voclosporin than with placebo (169 vs 372 days; log rank P < .001).

And voclosporin was well tolerated. The percentage of serious adverse events was similar in the voclosporin and placebo groups (20.8% vs 21.3%), with infection being the most common serious event (10.1% vs 11.2%).

In the voclosporin group, there were no significant differences between baseline and 1 year estimated glomerular filtration rates (eGFR), blood pressure, lipid levels, or sugar levels.

And there were fewer deaths in the voclosporin group than in the placebo group (1 vs 5).

Benefits were seen in all subgroups, including age, sex, race, biopsy class, geographic region of origin, and mycophenolate exposure at screening, Gibson reported.

Promise of a New Treatment

The promise of a new treatment is exciting for the field, said Joseph Vassalotti, MD, chief medical officer of the National Kidney Foundation.

However, it’s important to note that “this study is applicable only to patients with lupus nephritis with preserved kidney function,” he added.

An “eGFR less than 45 mL/min per 1.73 m² was implied as an exclusion criteria, so I would say it certainly doesn’t apply to patients with impaired kidney function,” he said, pointing out that this will be clearer when the final data are published.

The study cohort was heterogeneous; 86% of participants had class 3 or 4 biopsy findings and 14% had class 5, so the superiority of voclosporin is convincing, he said.

“We look forward to full publication and more details,” he told Medscape Medical News. “They do have an extension study, and it will be interesting to see how that plays out.”

Voclosporin was granted Fast Track designation by the US Food and Drug Administration in 2016, and these positive phase 3 results mean that a New Drug Application will likely be filed in the next few months. If approved, the drug could be on the market by 2021, according to a press release from Aurinia.

Nephrologists are familiar with calcineurin inhibitors, so it will be interesting to see, given the success of this trial, if voclosporin has a potential role in other kidney diseases, “such as minimal change disease,” said Vassalotti.

He added that there are concerns, unrelated to the AURORA trial, about the supply of hydroxychloroquine, which is also used for the treatment of lupus nephritis. “An overarching concern is that the supply will be limited now that the drug is being studied and used as prophylaxis after exposure to SARS-CoV-2 and as a treatment for COVID-19, creating challenges for patients with lupus nephritis trying to obtain their needed medication,” he said.

Gibson reports no relevant financial relationships. Two coauthors work for the drugmaker, Aurinia. Vassalotti reports no relevant financial relationships.
 

This article first appeared on Medscape.com.

For patients with lupus nephritis, kidney response improves when voclosporin (Aurinia Pharmaceuticals) is added to mycophenolate and low-dose corticosteroids, results from the phase 3 AURORA trial show.
 

The calcineurin inhibitor is the first novel agent to demonstrate effectiveness in the treatment of people with lupus nephritis, a disease that can lead to irreversible kidney damage, kidney failure, and even death.

“We believe that voclosporin – as an add-on therapy – will help more patients achieve remission,” said Keisha Gibson, MD, MPH, chief of pediatric nephrology at the UNC Kidney Center in Chapel Hill, North Carolina, who led the study and presented the findings during a virtual session at the National Kidney Foundation 2020 Spring Clinical Meetings.

The burden that lupus places on patients and the health system is high, she reported. Patients with lupus and uncontrolled kidney disease frequently have complications that require hospitalization, can suffer complete or partial loss of income, and can become temporarily disabled. And up to 50% of lupus patients will develop lupus nephritis.

“When we are lucky and see early treatment responses in our patients, we know that their long-term outcomes, measured by proteinuria reduction, are quite good,” said Gibson. “Unfortunately, in 10% to 30% of patients, despite standard-of-care therapies, we see progression to end-stage kidney disease within 15 years of diagnosis. This confers a huge cost to overall health and quality of life, and is an excess burden to the healthcare system.

“It is clear that one of the biggest risk factors for these patients who have kidney disease that is progressing to kidney failure is an inability to control the inflammation and chronic damage from uncontrolled disease,” she told Medscape Medical News.

“While there have certainly been a few advances in the care of patients with lupus disease, I believe that this therapy may help move the needle, specifically for patients with kidney involvement from their lupus disease,” she added.

Renal Response Much Higher With Voclosporin

The typical standard of care for patients with active lupus and kidney disease is either a combination of cyclophosphamide plus steroids or a combination of mycophenolate mofetil plus steroids.

The global, double-blind, randomized, placebo-controlled trial compared the effectiveness and safety of twice-daily oral voclosporin 23.7 mg with placebo. All 357 study participants also received mycophenolate 2 g daily and rapidly tapered low-dose oral corticosteroids.

At 1 year, the renal response rate was higher in the voclosporin group than in the placebo group (40.8% vs 22.5%; odds ratio, 2.65; P < .001).

“AURORA patients achieved low levels of protein twice as quickly as patients on standard of care,” the researchers write in their abstract. Median time to the achievement of a urine protein to creatinine ratio below 0.5 mg/mg was significantly and clinically better with voclosporin than with placebo (169 vs 372 days; log rank P < .001).

And voclosporin was well tolerated. The percentage of serious adverse events was similar in the voclosporin and placebo groups (20.8% vs 21.3%), with infection being the most common serious event (10.1% vs 11.2%).

In the voclosporin group, there were no significant differences between baseline and 1 year estimated glomerular filtration rates (eGFR), blood pressure, lipid levels, or sugar levels.

And there were fewer deaths in the voclosporin group than in the placebo group (1 vs 5).

Benefits were seen in all subgroups, including age, sex, race, biopsy class, geographic region of origin, and mycophenolate exposure at screening, Gibson reported.

Promise of a New Treatment

The promise of a new treatment is exciting for the field, said Joseph Vassalotti, MD, chief medical officer of the National Kidney Foundation.

However, it’s important to note that “this study is applicable only to patients with lupus nephritis with preserved kidney function,” he added.

An “eGFR less than 45 mL/min per 1.73 m² was implied as an exclusion criteria, so I would say it certainly doesn’t apply to patients with impaired kidney function,” he said, pointing out that this will be clearer when the final data are published.

The study cohort was heterogeneous; 86% of participants had class 3 or 4 biopsy findings and 14% had class 5, so the superiority of voclosporin is convincing, he said.

“We look forward to full publication and more details,” he told Medscape Medical News. “They do have an extension study, and it will be interesting to see how that plays out.”

Voclosporin was granted Fast Track designation by the US Food and Drug Administration in 2016, and these positive phase 3 results mean that a New Drug Application will likely be filed in the next few months. If approved, the drug could be on the market by 2021, according to a press release from Aurinia.

Nephrologists are familiar with calcineurin inhibitors, so it will be interesting to see, given the success of this trial, if voclosporin has a potential role in other kidney diseases, “such as minimal change disease,” said Vassalotti.

He added that there are concerns, unrelated to the AURORA trial, about the supply of hydroxychloroquine, which is also used for the treatment of lupus nephritis. “An overarching concern is that the supply will be limited now that the drug is being studied and used as prophylaxis after exposure to SARS-CoV-2 and as a treatment for COVID-19, creating challenges for patients with lupus nephritis trying to obtain their needed medication,” he said.

Gibson reports no relevant financial relationships. Two coauthors work for the drugmaker, Aurinia. Vassalotti reports no relevant financial relationships.
 

This article first appeared on Medscape.com.

Among patients who undergo endobronchial ultrasound-guided transbronchial biopsy using a guide sheath (EBUS-GS-TBB) for diagnosing lung cancer, cavitation and low-density areas inside the target lesion on CT and stenosis of the responsible bronchus are risk factors for infection after the procedure, according to a study published in CHEST.

“Infectious complications after [transbronchial biopsy] constitute a serious clinical problem because they might delay the start of treatment or cause the intended treatment to be modified to a milder one,” said Tomohide Souma, MD, of the department of respiratory medicine at Fujita Health University in Toyoake, Japan, and colleagues. “The precise mechanism of such complications is still unclear, and effective prophylaxis procedures have not been established. ... Thus, it is very important to identify the risk factors for infectious complications after TBB if and when these complications are to be avoided.”

To evaluate potential risk factors for infectious complications after EBUS-GS-TBB in a large sample of patients, Dr. Souma and colleagues retrospectively studied the medical records of 1,045 consecutive patients (median age, 72; 68% male) who underwent EBUS-GS-TBB between January 2013 and December 2017 at Fujita Health University Hospital.

In all, 47 patients developed infections, a cumulative incidence of about 4.5%. Infections included pneumonia (51.1%), intratumoral infection (29.8%), and three cases each of lung abscess, pleurisy, and empyema. Three patients, two with empyema and one with lung abscess, died within 1 month before administration of anticancer treatment. “In total, more than 40% of patients with post–EBUS-GS-TBB infection were unable to receive preplanned anticancer treatment,” the researchers said.

On multivariate analysis, cavitation in the lesion (odds ratio, 3.63), low-density areas in the lesion (OR, 13.26), and bronchoscopic findings of responsible bronchus stenosis (OR, 7.82) were significantly associated with development of infections post biopsy.

An analysis that matched 89 patients who received prophylactic antibiotics with controls who did not receive prophylactic antibiotics did not find that prophylactic antibiotics significantly reduced the likelihood of post–EBUS-GS-TBB infection.

“Notably, three risk factors found in our study indicate that the inflammation-prone status of lesions may be the most important factor for developing post–EBUS-TBB infection,” Dr. Souma and colleagues said. “Although our study does not rebuff the role of antibiotics in postbronchoscopy infection therapy, clinicians should notify patients that post-TBB infection may occur despite the use of prophylactic antibiotics. We recommend that careful and frequent follow-up be applied to patients undergoing diagnostic EBUS-GS-TBB with reference to the risk factors identified in our study.”

A. Christine Argento, MD, FCCP, assistant professor of medicine and thoracic surgery and director of the interventional pulmonary fellowship program at Northwestern University, Chicago, noted that this is an important study on a topic that has not been well described in the past.

jremaly@mdedge.com

SOURCE: Souma T et al. CHEST. 2020 Mar 4. doi: 10.1016/j.chest.2020.02.025.

Among patients who undergo endobronchial ultrasound-guided transbronchial biopsy using a guide sheath (EBUS-GS-TBB) for diagnosing lung cancer, cavitation and low-density areas inside the target lesion on CT and stenosis of the responsible bronchus are risk factors for infection after the procedure, according to a study published in CHEST.

“Infectious complications after [transbronchial biopsy] constitute a serious clinical problem because they might delay the start of treatment or cause the intended treatment to be modified to a milder one,” said Tomohide Souma, MD, of the department of respiratory medicine at Fujita Health University in Toyoake, Japan, and colleagues. “The precise mechanism of such complications is still unclear, and effective prophylaxis procedures have not been established. ... Thus, it is very important to identify the risk factors for infectious complications after TBB if and when these complications are to be avoided.”

To evaluate potential risk factors for infectious complications after EBUS-GS-TBB in a large sample of patients, Dr. Souma and colleagues retrospectively studied the medical records of 1,045 consecutive patients (median age, 72; 68% male) who underwent EBUS-GS-TBB between January 2013 and December 2017 at Fujita Health University Hospital.

In all, 47 patients developed infections, a cumulative incidence of about 4.5%. Infections included pneumonia (51.1%), intratumoral infection (29.8%), and three cases each of lung abscess, pleurisy, and empyema. Three patients, two with empyema and one with lung abscess, died within 1 month before administration of anticancer treatment. “In total, more than 40% of patients with post–EBUS-GS-TBB infection were unable to receive preplanned anticancer treatment,” the researchers said.

On multivariate analysis, cavitation in the lesion (odds ratio, 3.63), low-density areas in the lesion (OR, 13.26), and bronchoscopic findings of responsible bronchus stenosis (OR, 7.82) were significantly associated with development of infections post biopsy.

An analysis that matched 89 patients who received prophylactic antibiotics with controls who did not receive prophylactic antibiotics did not find that prophylactic antibiotics significantly reduced the likelihood of post–EBUS-GS-TBB infection.

“Notably, three risk factors found in our study indicate that the inflammation-prone status of lesions may be the most important factor for developing post–EBUS-TBB infection,” Dr. Souma and colleagues said. “Although our study does not rebuff the role of antibiotics in postbronchoscopy infection therapy, clinicians should notify patients that post-TBB infection may occur despite the use of prophylactic antibiotics. We recommend that careful and frequent follow-up be applied to patients undergoing diagnostic EBUS-GS-TBB with reference to the risk factors identified in our study.”

A. Christine Argento, MD, FCCP, assistant professor of medicine and thoracic surgery and director of the interventional pulmonary fellowship program at Northwestern University, Chicago, noted that this is an important study on a topic that has not been well described in the past.

jremaly@mdedge.com

SOURCE: Souma T et al. CHEST. 2020 Mar 4. doi: 10.1016/j.chest.2020.02.025.

Among patients who undergo endobronchial ultrasound-guided transbronchial biopsy using a guide sheath (EBUS-GS-TBB) for diagnosing lung cancer, cavitation and low-density areas inside the target lesion on CT and stenosis of the responsible bronchus are risk factors for infection after the procedure, according to a study published in CHEST.

“Infectious complications after [transbronchial biopsy] constitute a serious clinical problem because they might delay the start of treatment or cause the intended treatment to be modified to a milder one,” said Tomohide Souma, MD, of the department of respiratory medicine at Fujita Health University in Toyoake, Japan, and colleagues. “The precise mechanism of such complications is still unclear, and effective prophylaxis procedures have not been established. ... Thus, it is very important to identify the risk factors for infectious complications after TBB if and when these complications are to be avoided.”

To evaluate potential risk factors for infectious complications after EBUS-GS-TBB in a large sample of patients, Dr. Souma and colleagues retrospectively studied the medical records of 1,045 consecutive patients (median age, 72; 68% male) who underwent EBUS-GS-TBB between January 2013 and December 2017 at Fujita Health University Hospital.

In all, 47 patients developed infections, a cumulative incidence of about 4.5%. Infections included pneumonia (51.1%), intratumoral infection (29.8%), and three cases each of lung abscess, pleurisy, and empyema. Three patients, two with empyema and one with lung abscess, died within 1 month before administration of anticancer treatment. “In total, more than 40% of patients with post–EBUS-GS-TBB infection were unable to receive preplanned anticancer treatment,” the researchers said.

On multivariate analysis, cavitation in the lesion (odds ratio, 3.63), low-density areas in the lesion (OR, 13.26), and bronchoscopic findings of responsible bronchus stenosis (OR, 7.82) were significantly associated with development of infections post biopsy.

An analysis that matched 89 patients who received prophylactic antibiotics with controls who did not receive prophylactic antibiotics did not find that prophylactic antibiotics significantly reduced the likelihood of post–EBUS-GS-TBB infection.

“Notably, three risk factors found in our study indicate that the inflammation-prone status of lesions may be the most important factor for developing post–EBUS-TBB infection,” Dr. Souma and colleagues said. “Although our study does not rebuff the role of antibiotics in postbronchoscopy infection therapy, clinicians should notify patients that post-TBB infection may occur despite the use of prophylactic antibiotics. We recommend that careful and frequent follow-up be applied to patients undergoing diagnostic EBUS-GS-TBB with reference to the risk factors identified in our study.”

A. Christine Argento, MD, FCCP, assistant professor of medicine and thoracic surgery and director of the interventional pulmonary fellowship program at Northwestern University, Chicago, noted that this is an important study on a topic that has not been well described in the past.

jremaly@mdedge.com

SOURCE: Souma T et al. CHEST. 2020 Mar 4. doi: 10.1016/j.chest.2020.02.025.

Catheter-based renal denervation took a step closer to attaining legitimacy as a nonpharmacologic treatment for hypertension with presentation of the primary results of the SPYRAL HTN-OFF MED pivotal trial 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.

Mohammed Haneefa Nizamudeen/Getty Images

“We saw clinically meaningful blood pressure reductions at 3 months,” reported Michael Boehm, MD, chief of cardiology at Saarland University Hospital in Homburg, Germany.

That’s encouraging news, as renal denervation (RDN) was nearly abandoned as a potential treatment for hypertension in the wake of the unexpectedly negative results of the SYMPLICITY HTN-3 trial (N Engl J Med. 2014;370:1393-401). However, post hoc analysis of the trial revealed significant shortcomings in design and execution, and a more rigorous development program for the percutaneous device-based therapy is well underway.

The SPYRAL HTN-OFF MED pivotal trial was designed under Food and Drug Administration guidance to show whether RDN reduces blood pressure in patients with untreated hypertension. The prospective study included 331 off-medication patients in nine countries who were randomized to RDN or a sham procedure, then followed in double-blind fashion for 3 months.

The primary outcome was change in 24-hour ambulatory systolic blood pressure from baseline to 3 months. From a mean baseline 24-hour ambulatory blood pressure of 151.4/98 mm Hg, patients in the RDN group averaged a 4.7 mm Hg decrease in 24-hour SBP, which was 4 mm Hg more than in sham-treated controls. Statistically, this translated to a greater than 99.9% probability that RDN was superior to sham therapy. The RDN group also experienced a mean 3.7–mm Hg reduction in 24-hour DBP, compared with a 0.8–mm Hg decrease in controls.

Office SBP – the secondary endpoint – decreased by a mean of 9.2 mm Hg with RDN, compared with 2.5 mm Hg in controls.

These results probably understate the true antihypertensive effect of RDN for two reasons, Dr. Boehm noted. For one, previous studies have shown that the magnitude of blood pressure lowering continues to increase for up to 1-2 years following the procedure, whereas the off-medication assessment in SPYRAL HTN-OFF MED ended at 3 months for ethical and safety reasons. Also, 17% of patients in the control arm were withdrawn from the study and placed on antihypertensive medication because their office SBP reached 180 mm Hg or more, as compared to 9.6% of the RDN group.

A key finding was that RDN lowered blood pressure around the clock, including nighttime and early morning, the hours of greatest cardiovascular risk and a time when some antihypertensive medications are less effective at blood pressure control, the cardiologist observed.

The RDN safety picture was reassuring, with no strokes, myocardial infarctions, major bleeding, or acute deterioration in kidney function.

A surprising finding was that, even though participants underwent blood and urine testing for the presence of antihypertensive drugs at baseline to ensure they were off medication, and were told they would be retested at 3 months, 5%-9% nonetheless tested positive at the second test.

That elicited a comment from session chair Richard A. Chazal, MD, of Fort Myers, Fla.: “I must say, as a clinician who sometimes has trouble getting his patients to take antihypertensives, it’s fascinating that some of the people that you asked not to take the medications were taking them.”

While the primary outcome in SPYRAL HTN-OFF MED was the 3-month reduction in blood pressure while off of antihypertensive medication, the ongoing second phase of the trial may have greater clinical relevance. At 3 months, participants are being placed on antihypertensive medication and uptitrated to target, with unblinding at 6 months. The purpose is to see how many RDN recipients don’t need antihypertensive drugs, as well as whether those that do require less medication than the patients who didn’t undergo RDN.

Dr. Boehm characterized RDN as a work in progress. Two major limitations that are the focus of intense research are the lack of a predictor as to which patients are most likely to respond to what is after all an invasive procedure, and the current inability intraprocedurally to tell if sufficient RDN has been achieved.

“Frankly speaking, there is no technology during the procedure to see how efficacious the procedure was,” he explained.

Discussant Dhanunaja Lakkireddy, MD, deemed the mean 4.7–mm Hg reduction in 24-hour SBP “reasonably impressive – that’s actually a pretty good number for an antihypertensive clinical trial.” He was also favorably impressed by RDN’s safety in a 44-site study.

“The drops in blood pressure are not enough to really make a case for renal denervation to be a standalone therapy. But adding it as an adjunct to standard medications may be a very reasonable strategy to adopt. This is a fantastic signal for something that can be brought along as a long-term add-on to antihypertensive medications,” commented Dr. Lakkireddy, chair of the ACC Electrophysiology Council and medical director of the Kansas City Heart Rhythm Institute.

Simultaneous with Dr. Boehm’s presentation, the SPYRAL HTN-OFF MED Pivotal Trial details were published online (Lancet 2020 Mar 29. doi: 10.1016/S0140-6736(20)30554-7).

The study was sponsored by Medtronic. Dr. Boehm reported serving as a consultant to that company and Abbott, Amgen, Astra, Boehringer-Ingelheim, Cytokinetics, Novartis, ReCor, Servier, and Vifor.

bjancin@mdedge.com

SOURCE: Boehm M. ACC 2020, Abstract 406-15.

Catheter-based renal denervation took a step closer to attaining legitimacy as a nonpharmacologic treatment for hypertension with presentation of the primary results of the SPYRAL HTN-OFF MED pivotal trial 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.

Mohammed Haneefa Nizamudeen/Getty Images

“We saw clinically meaningful blood pressure reductions at 3 months,” reported Michael Boehm, MD, chief of cardiology at Saarland University Hospital in Homburg, Germany.

That’s encouraging news, as renal denervation (RDN) was nearly abandoned as a potential treatment for hypertension in the wake of the unexpectedly negative results of the SYMPLICITY HTN-3 trial (N Engl J Med. 2014;370:1393-401). However, post hoc analysis of the trial revealed significant shortcomings in design and execution, and a more rigorous development program for the percutaneous device-based therapy is well underway.

The SPYRAL HTN-OFF MED pivotal trial was designed under Food and Drug Administration guidance to show whether RDN reduces blood pressure in patients with untreated hypertension. The prospective study included 331 off-medication patients in nine countries who were randomized to RDN or a sham procedure, then followed in double-blind fashion for 3 months.

The primary outcome was change in 24-hour ambulatory systolic blood pressure from baseline to 3 months. From a mean baseline 24-hour ambulatory blood pressure of 151.4/98 mm Hg, patients in the RDN group averaged a 4.7 mm Hg decrease in 24-hour SBP, which was 4 mm Hg more than in sham-treated controls. Statistically, this translated to a greater than 99.9% probability that RDN was superior to sham therapy. The RDN group also experienced a mean 3.7–mm Hg reduction in 24-hour DBP, compared with a 0.8–mm Hg decrease in controls.

Office SBP – the secondary endpoint – decreased by a mean of 9.2 mm Hg with RDN, compared with 2.5 mm Hg in controls.

These results probably understate the true antihypertensive effect of RDN for two reasons, Dr. Boehm noted. For one, previous studies have shown that the magnitude of blood pressure lowering continues to increase for up to 1-2 years following the procedure, whereas the off-medication assessment in SPYRAL HTN-OFF MED ended at 3 months for ethical and safety reasons. Also, 17% of patients in the control arm were withdrawn from the study and placed on antihypertensive medication because their office SBP reached 180 mm Hg or more, as compared to 9.6% of the RDN group.

A key finding was that RDN lowered blood pressure around the clock, including nighttime and early morning, the hours of greatest cardiovascular risk and a time when some antihypertensive medications are less effective at blood pressure control, the cardiologist observed.

The RDN safety picture was reassuring, with no strokes, myocardial infarctions, major bleeding, or acute deterioration in kidney function.

A surprising finding was that, even though participants underwent blood and urine testing for the presence of antihypertensive drugs at baseline to ensure they were off medication, and were told they would be retested at 3 months, 5%-9% nonetheless tested positive at the second test.

That elicited a comment from session chair Richard A. Chazal, MD, of Fort Myers, Fla.: “I must say, as a clinician who sometimes has trouble getting his patients to take antihypertensives, it’s fascinating that some of the people that you asked not to take the medications were taking them.”

While the primary outcome in SPYRAL HTN-OFF MED was the 3-month reduction in blood pressure while off of antihypertensive medication, the ongoing second phase of the trial may have greater clinical relevance. At 3 months, participants are being placed on antihypertensive medication and uptitrated to target, with unblinding at 6 months. The purpose is to see how many RDN recipients don’t need antihypertensive drugs, as well as whether those that do require less medication than the patients who didn’t undergo RDN.

Dr. Boehm characterized RDN as a work in progress. Two major limitations that are the focus of intense research are the lack of a predictor as to which patients are most likely to respond to what is after all an invasive procedure, and the current inability intraprocedurally to tell if sufficient RDN has been achieved.

“Frankly speaking, there is no technology during the procedure to see how efficacious the procedure was,” he explained.

Discussant Dhanunaja Lakkireddy, MD, deemed the mean 4.7–mm Hg reduction in 24-hour SBP “reasonably impressive – that’s actually a pretty good number for an antihypertensive clinical trial.” He was also favorably impressed by RDN’s safety in a 44-site study.

“The drops in blood pressure are not enough to really make a case for renal denervation to be a standalone therapy. But adding it as an adjunct to standard medications may be a very reasonable strategy to adopt. This is a fantastic signal for something that can be brought along as a long-term add-on to antihypertensive medications,” commented Dr. Lakkireddy, chair of the ACC Electrophysiology Council and medical director of the Kansas City Heart Rhythm Institute.

Simultaneous with Dr. Boehm’s presentation, the SPYRAL HTN-OFF MED Pivotal Trial details were published online (Lancet 2020 Mar 29. doi: 10.1016/S0140-6736(20)30554-7).

The study was sponsored by Medtronic. Dr. Boehm reported serving as a consultant to that company and Abbott, Amgen, Astra, Boehringer-Ingelheim, Cytokinetics, Novartis, ReCor, Servier, and Vifor.

bjancin@mdedge.com

SOURCE: Boehm M. ACC 2020, Abstract 406-15.

Catheter-based renal denervation took a step closer to attaining legitimacy as a nonpharmacologic treatment for hypertension with presentation of the primary results of the SPYRAL HTN-OFF MED pivotal trial 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.

Mohammed Haneefa Nizamudeen/Getty Images

“We saw clinically meaningful blood pressure reductions at 3 months,” reported Michael Boehm, MD, chief of cardiology at Saarland University Hospital in Homburg, Germany.

That’s encouraging news, as renal denervation (RDN) was nearly abandoned as a potential treatment for hypertension in the wake of the unexpectedly negative results of the SYMPLICITY HTN-3 trial (N Engl J Med. 2014;370:1393-401). However, post hoc analysis of the trial revealed significant shortcomings in design and execution, and a more rigorous development program for the percutaneous device-based therapy is well underway.

The SPYRAL HTN-OFF MED pivotal trial was designed under Food and Drug Administration guidance to show whether RDN reduces blood pressure in patients with untreated hypertension. The prospective study included 331 off-medication patients in nine countries who were randomized to RDN or a sham procedure, then followed in double-blind fashion for 3 months.

The primary outcome was change in 24-hour ambulatory systolic blood pressure from baseline to 3 months. From a mean baseline 24-hour ambulatory blood pressure of 151.4/98 mm Hg, patients in the RDN group averaged a 4.7 mm Hg decrease in 24-hour SBP, which was 4 mm Hg more than in sham-treated controls. Statistically, this translated to a greater than 99.9% probability that RDN was superior to sham therapy. The RDN group also experienced a mean 3.7–mm Hg reduction in 24-hour DBP, compared with a 0.8–mm Hg decrease in controls.

Office SBP – the secondary endpoint – decreased by a mean of 9.2 mm Hg with RDN, compared with 2.5 mm Hg in controls.

These results probably understate the true antihypertensive effect of RDN for two reasons, Dr. Boehm noted. For one, previous studies have shown that the magnitude of blood pressure lowering continues to increase for up to 1-2 years following the procedure, whereas the off-medication assessment in SPYRAL HTN-OFF MED ended at 3 months for ethical and safety reasons. Also, 17% of patients in the control arm were withdrawn from the study and placed on antihypertensive medication because their office SBP reached 180 mm Hg or more, as compared to 9.6% of the RDN group.

A key finding was that RDN lowered blood pressure around the clock, including nighttime and early morning, the hours of greatest cardiovascular risk and a time when some antihypertensive medications are less effective at blood pressure control, the cardiologist observed.

The RDN safety picture was reassuring, with no strokes, myocardial infarctions, major bleeding, or acute deterioration in kidney function.

A surprising finding was that, even though participants underwent blood and urine testing for the presence of antihypertensive drugs at baseline to ensure they were off medication, and were told they would be retested at 3 months, 5%-9% nonetheless tested positive at the second test.

That elicited a comment from session chair Richard A. Chazal, MD, of Fort Myers, Fla.: “I must say, as a clinician who sometimes has trouble getting his patients to take antihypertensives, it’s fascinating that some of the people that you asked not to take the medications were taking them.”

While the primary outcome in SPYRAL HTN-OFF MED was the 3-month reduction in blood pressure while off of antihypertensive medication, the ongoing second phase of the trial may have greater clinical relevance. At 3 months, participants are being placed on antihypertensive medication and uptitrated to target, with unblinding at 6 months. The purpose is to see how many RDN recipients don’t need antihypertensive drugs, as well as whether those that do require less medication than the patients who didn’t undergo RDN.

Dr. Boehm characterized RDN as a work in progress. Two major limitations that are the focus of intense research are the lack of a predictor as to which patients are most likely to respond to what is after all an invasive procedure, and the current inability intraprocedurally to tell if sufficient RDN has been achieved.

“Frankly speaking, there is no technology during the procedure to see how efficacious the procedure was,” he explained.

Discussant Dhanunaja Lakkireddy, MD, deemed the mean 4.7–mm Hg reduction in 24-hour SBP “reasonably impressive – that’s actually a pretty good number for an antihypertensive clinical trial.” He was also favorably impressed by RDN’s safety in a 44-site study.

“The drops in blood pressure are not enough to really make a case for renal denervation to be a standalone therapy. But adding it as an adjunct to standard medications may be a very reasonable strategy to adopt. This is a fantastic signal for something that can be brought along as a long-term add-on to antihypertensive medications,” commented Dr. Lakkireddy, chair of the ACC Electrophysiology Council and medical director of the Kansas City Heart Rhythm Institute.

Simultaneous with Dr. Boehm’s presentation, the SPYRAL HTN-OFF MED Pivotal Trial details were published online (Lancet 2020 Mar 29. doi: 10.1016/S0140-6736(20)30554-7).

The study was sponsored by Medtronic. Dr. Boehm reported serving as a consultant to that company and Abbott, Amgen, Astra, Boehringer-Ingelheim, Cytokinetics, Novartis, ReCor, Servier, and Vifor.

bjancin@mdedge.com

SOURCE: Boehm M. ACC 2020, Abstract 406-15.

The long-sought goal of measuring the quality of U.S. transcatheter aortic valve replacement (TAVR) programs by patient outcomes rather than by the surrogate measure of case volume is about to be realized.

Starting more or less immediately, the U.S. national register for all TAVR cases that’s mandated by Food and Drug Administration labeling of these devices and run through a collaboration of the American College of Cardiology and the Society of Thoracic Surgeons will start applying a newly developed and validated five-item metric for measuring 30-day patient outcomes and designed to gauge the quality of TAVR programs.

At first, the only recipients of the data will be the programs themselves, but starting in about a year, by sometime in 2021, the STS/ACC TVT (transcatheter valve therapy) Registry will start to make its star-based rating of TAVR programs available to the public, Nimesh D. Desai, MD, said on March 29 at the joint scientific sessions of the ACC and the World Heart Federation. The meeting was conducted online after its cancellation because of the COVID-19 pandemic. These societies already make star-based ratings of U.S. programs available to the public for several other types of cardiac interventions, including coronary artery bypass surgery and MI management.

The new, composite metric based on 30-day outcome data “is appropriate for high-stakes applications such as public reporting,” said Dr. Desai, a thoracic surgeon and director of thoracic aortic surgery research at the University of Pennsylvania in Philadelphia. “We’re confident this model can be used for public reporting. It’s undergone extensive testing of its validity.” The steering committee of the STS/ACC TVT Registry commissioned development of the metric, and it’s now “considered approved,” and ready for use, he explained.

To create the new metric, Dr. Desai and his associates used data from 52,561 patients who underwent transfemoral TAVR during 2015-2017 at any of 301 U.S. sites. These data came from a total pool of more than 114,000 patients at 556 sites, but data from many sites weren’t usable because they were not adequately complete. The researchers then identified the top four measures taken during the 30 days following intervention (hospitalization included) that best correlated with 1-year survival and patients’ quality-of-life scores on the Kansas City Cardiomyopathy Questionnaire: stroke; major, life-threatening, or disabling bleed; acute kidney injury (stage III); and moderate or severe paravalvular leak. These outcomes “matter most to patients,” Dr. Desai said.

They used these four outcomes plus 30-day mortality to calculate the programs’ ratings. Among the 52,561 patients, 14% had at least one of these adverse outcomes. The researchers then used a logistic regression model that adjusted for 46 measured variables to calculate how each program performed relative to the average performance of all the programs. Programs with outcomes that fell within the 95% confidence intervals of average performance were rated as performing as expected; those outside rated as performing either better or worse than expected. The results showed 34 centers (11%) had worse than expected outcomes and 25 (8%) had better than expected outcomes, Dr. Desai said.

“This is a major step forward in measuring TAVR quality,” commented Michael Mack, MD, a cardiac surgeon with Baylor Scott & White Health in Dallas who has been very active in studying TAVR. “Until now, we used volume as a surrogate for quality, but the precision was not great. This is an extremely welcome metric.” The next step is to eventually use 1-year follow-up data instead of 30-day outcomes, he added.

“With the rapid expansion of TAVR over the past 6-8 years, we’re now at the point to start to do this. It’s an ethical obligation This will be one of the most high-fidelity, valid models for public reporting” of clinical outcomes,” said Joseph Cleveland, MD, a professor of surgery at the University of Colorado at Denver in Aurora. “It’s reassuring that about 90% of the program performed as expected or better than expected,” he added.

“Transparency and outcomes should drive how TAVR is delivered,” commented Ashish Pershad, MD, an interventional cardiologist at Banner-University Medicine Heart Institute in Phoenix who estimated that he performs about 150 TAVR procedures annually. “This is a step forward. I’ve been waiting for this for a long time. Until now, volume has been used as a surrogate outcome, but we know it’s not accurate. I’m confident that this model is a good starting point.” But Dr. Pershad also had concern that this new approach “can lend itself to some degree of gaming,” like a bleeding event getting classified as minor when it was really major, or outlier patients getting dropped from reports.

The temptation to cut corners may be higher for TAVR than it’s been for the cardiac-disease metrics that already get publicly reported, like bypass surgery and myocardial infarction management, because of TAVR’s higher cost and higher profile, Dr. Pershad said. Existing measures “have not been as linked to financial disincentive as TAVR might be” because TAVR reimbursements can run as high as $50,000 per case. “The stakes with TAVR are higher,” he said.

Ultimately, the reliable examination of TAVR outcomes that this new metric allows may lead to a shake-up of TAVR programs, Dr. Pershad predicted. “This is clearly a step toward closing down some programs that [consistently] underperform.”

The STS/ACC TVT Registry receives no commercial funding. Dr. Desai has been a consultant to, speaker on behalf of, and received research funding from Gore, and he has also spoken on behalf of Cook, Medtronic, and Terumo Aortic. Dr. Cleveland, Dr. Mack, and Dr. Pershad had no disclosures.

mzoler@mdedge.com

The long-sought goal of measuring the quality of U.S. transcatheter aortic valve replacement (TAVR) programs by patient outcomes rather than by the surrogate measure of case volume is about to be realized.

Starting more or less immediately, the U.S. national register for all TAVR cases that’s mandated by Food and Drug Administration labeling of these devices and run through a collaboration of the American College of Cardiology and the Society of Thoracic Surgeons will start applying a newly developed and validated five-item metric for measuring 30-day patient outcomes and designed to gauge the quality of TAVR programs.

At first, the only recipients of the data will be the programs themselves, but starting in about a year, by sometime in 2021, the STS/ACC TVT (transcatheter valve therapy) Registry will start to make its star-based rating of TAVR programs available to the public, Nimesh D. Desai, MD, said on March 29 at the joint scientific sessions of the ACC and the World Heart Federation. The meeting was conducted online after its cancellation because of the COVID-19 pandemic. These societies already make star-based ratings of U.S. programs available to the public for several other types of cardiac interventions, including coronary artery bypass surgery and MI management.

The new, composite metric based on 30-day outcome data “is appropriate for high-stakes applications such as public reporting,” said Dr. Desai, a thoracic surgeon and director of thoracic aortic surgery research at the University of Pennsylvania in Philadelphia. “We’re confident this model can be used for public reporting. It’s undergone extensive testing of its validity.” The steering committee of the STS/ACC TVT Registry commissioned development of the metric, and it’s now “considered approved,” and ready for use, he explained.

To create the new metric, Dr. Desai and his associates used data from 52,561 patients who underwent transfemoral TAVR during 2015-2017 at any of 301 U.S. sites. These data came from a total pool of more than 114,000 patients at 556 sites, but data from many sites weren’t usable because they were not adequately complete. The researchers then identified the top four measures taken during the 30 days following intervention (hospitalization included) that best correlated with 1-year survival and patients’ quality-of-life scores on the Kansas City Cardiomyopathy Questionnaire: stroke; major, life-threatening, or disabling bleed; acute kidney injury (stage III); and moderate or severe paravalvular leak. These outcomes “matter most to patients,” Dr. Desai said.

They used these four outcomes plus 30-day mortality to calculate the programs’ ratings. Among the 52,561 patients, 14% had at least one of these adverse outcomes. The researchers then used a logistic regression model that adjusted for 46 measured variables to calculate how each program performed relative to the average performance of all the programs. Programs with outcomes that fell within the 95% confidence intervals of average performance were rated as performing as expected; those outside rated as performing either better or worse than expected. The results showed 34 centers (11%) had worse than expected outcomes and 25 (8%) had better than expected outcomes, Dr. Desai said.

“This is a major step forward in measuring TAVR quality,” commented Michael Mack, MD, a cardiac surgeon with Baylor Scott & White Health in Dallas who has been very active in studying TAVR. “Until now, we used volume as a surrogate for quality, but the precision was not great. This is an extremely welcome metric.” The next step is to eventually use 1-year follow-up data instead of 30-day outcomes, he added.

“With the rapid expansion of TAVR over the past 6-8 years, we’re now at the point to start to do this. It’s an ethical obligation This will be one of the most high-fidelity, valid models for public reporting” of clinical outcomes,” said Joseph Cleveland, MD, a professor of surgery at the University of Colorado at Denver in Aurora. “It’s reassuring that about 90% of the program performed as expected or better than expected,” he added.

“Transparency and outcomes should drive how TAVR is delivered,” commented Ashish Pershad, MD, an interventional cardiologist at Banner-University Medicine Heart Institute in Phoenix who estimated that he performs about 150 TAVR procedures annually. “This is a step forward. I’ve been waiting for this for a long time. Until now, volume has been used as a surrogate outcome, but we know it’s not accurate. I’m confident that this model is a good starting point.” But Dr. Pershad also had concern that this new approach “can lend itself to some degree of gaming,” like a bleeding event getting classified as minor when it was really major, or outlier patients getting dropped from reports.

The temptation to cut corners may be higher for TAVR than it’s been for the cardiac-disease metrics that already get publicly reported, like bypass surgery and myocardial infarction management, because of TAVR’s higher cost and higher profile, Dr. Pershad said. Existing measures “have not been as linked to financial disincentive as TAVR might be” because TAVR reimbursements can run as high as $50,000 per case. “The stakes with TAVR are higher,” he said.

Ultimately, the reliable examination of TAVR outcomes that this new metric allows may lead to a shake-up of TAVR programs, Dr. Pershad predicted. “This is clearly a step toward closing down some programs that [consistently] underperform.”

The STS/ACC TVT Registry receives no commercial funding. Dr. Desai has been a consultant to, speaker on behalf of, and received research funding from Gore, and he has also spoken on behalf of Cook, Medtronic, and Terumo Aortic. Dr. Cleveland, Dr. Mack, and Dr. Pershad had no disclosures.

mzoler@mdedge.com

The long-sought goal of measuring the quality of U.S. transcatheter aortic valve replacement (TAVR) programs by patient outcomes rather than by the surrogate measure of case volume is about to be realized.

Starting more or less immediately, the U.S. national register for all TAVR cases that’s mandated by Food and Drug Administration labeling of these devices and run through a collaboration of the American College of Cardiology and the Society of Thoracic Surgeons will start applying a newly developed and validated five-item metric for measuring 30-day patient outcomes and designed to gauge the quality of TAVR programs.

At first, the only recipients of the data will be the programs themselves, but starting in about a year, by sometime in 2021, the STS/ACC TVT (transcatheter valve therapy) Registry will start to make its star-based rating of TAVR programs available to the public, Nimesh D. Desai, MD, said on March 29 at the joint scientific sessions of the ACC and the World Heart Federation. The meeting was conducted online after its cancellation because of the COVID-19 pandemic. These societies already make star-based ratings of U.S. programs available to the public for several other types of cardiac interventions, including coronary artery bypass surgery and MI management.

The new, composite metric based on 30-day outcome data “is appropriate for high-stakes applications such as public reporting,” said Dr. Desai, a thoracic surgeon and director of thoracic aortic surgery research at the University of Pennsylvania in Philadelphia. “We’re confident this model can be used for public reporting. It’s undergone extensive testing of its validity.” The steering committee of the STS/ACC TVT Registry commissioned development of the metric, and it’s now “considered approved,” and ready for use, he explained.

To create the new metric, Dr. Desai and his associates used data from 52,561 patients who underwent transfemoral TAVR during 2015-2017 at any of 301 U.S. sites. These data came from a total pool of more than 114,000 patients at 556 sites, but data from many sites weren’t usable because they were not adequately complete. The researchers then identified the top four measures taken during the 30 days following intervention (hospitalization included) that best correlated with 1-year survival and patients’ quality-of-life scores on the Kansas City Cardiomyopathy Questionnaire: stroke; major, life-threatening, or disabling bleed; acute kidney injury (stage III); and moderate or severe paravalvular leak. These outcomes “matter most to patients,” Dr. Desai said.

They used these four outcomes plus 30-day mortality to calculate the programs’ ratings. Among the 52,561 patients, 14% had at least one of these adverse outcomes. The researchers then used a logistic regression model that adjusted for 46 measured variables to calculate how each program performed relative to the average performance of all the programs. Programs with outcomes that fell within the 95% confidence intervals of average performance were rated as performing as expected; those outside rated as performing either better or worse than expected. The results showed 34 centers (11%) had worse than expected outcomes and 25 (8%) had better than expected outcomes, Dr. Desai said.

“This is a major step forward in measuring TAVR quality,” commented Michael Mack, MD, a cardiac surgeon with Baylor Scott & White Health in Dallas who has been very active in studying TAVR. “Until now, we used volume as a surrogate for quality, but the precision was not great. This is an extremely welcome metric.” The next step is to eventually use 1-year follow-up data instead of 30-day outcomes, he added.

“With the rapid expansion of TAVR over the past 6-8 years, we’re now at the point to start to do this. It’s an ethical obligation This will be one of the most high-fidelity, valid models for public reporting” of clinical outcomes,” said Joseph Cleveland, MD, a professor of surgery at the University of Colorado at Denver in Aurora. “It’s reassuring that about 90% of the program performed as expected or better than expected,” he added.

“Transparency and outcomes should drive how TAVR is delivered,” commented Ashish Pershad, MD, an interventional cardiologist at Banner-University Medicine Heart Institute in Phoenix who estimated that he performs about 150 TAVR procedures annually. “This is a step forward. I’ve been waiting for this for a long time. Until now, volume has been used as a surrogate outcome, but we know it’s not accurate. I’m confident that this model is a good starting point.” But Dr. Pershad also had concern that this new approach “can lend itself to some degree of gaming,” like a bleeding event getting classified as minor when it was really major, or outlier patients getting dropped from reports.

The temptation to cut corners may be higher for TAVR than it’s been for the cardiac-disease metrics that already get publicly reported, like bypass surgery and myocardial infarction management, because of TAVR’s higher cost and higher profile, Dr. Pershad said. Existing measures “have not been as linked to financial disincentive as TAVR might be” because TAVR reimbursements can run as high as $50,000 per case. “The stakes with TAVR are higher,” he said.

Ultimately, the reliable examination of TAVR outcomes that this new metric allows may lead to a shake-up of TAVR programs, Dr. Pershad predicted. “This is clearly a step toward closing down some programs that [consistently] underperform.”

The STS/ACC TVT Registry receives no commercial funding. Dr. Desai has been a consultant to, speaker on behalf of, and received research funding from Gore, and he has also spoken on behalf of Cook, Medtronic, and Terumo Aortic. Dr. Cleveland, Dr. Mack, and Dr. Pershad had no disclosures.

mzoler@mdedge.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.

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.

Transcatheter aortic valve replacement (TAVR) was not inferior to conventional surgery with respect to death from any cause at 1 year in a new real-world study in patients age 70 years or older with severe symptomatic aortic stenosis at increased operative risk due to age or comorbidity.

The UK TAVI study was presented March 29 at the “virtual” American College of Cardiology 2020 Scientific Session (ACC.20)/World Congress of Cardiology (WCC).

The trial involved a broad group of patients who were treated at every medical center that performs the transcatheter procedure across the United Kingdom.

“The importance of this trial is that it confirms the effectiveness of the TAVR strategy in a real-world setting,” said lead author, William D. Toff, MD, professor of cardiology at the University of Leicester, United Kingdom.

Previous clinical trials have found TAVR to be noninferior or superior to open-heart surgery for various patient groups, but most trials have been limited to medical centers that perform a high volume of procedures or focus on the use of specific types of replacement valves, he noted.

“Our results are concordant with those from earlier trials in intermediate- and low-risk patients, but those earlier trials were performed in the best centers and had many exclusion criteria. We have replicated those results in populations more representative of the real world.”

“I think it is a very important message that supports the findings in earlier trials that were focused on showing whether TAVR can work under ideal conditions, while our trial shows that it does work in real-world clinical practice,” he added.

The UK TAVI trial enrolled 913 patients referred for treatment of severe aortic stenosis at 34 UK sites from 2014 to 2018. They were randomly assigned to receive TAVR or open-heart surgery.

Enrollment was limited to participants age 70 years or older (with additional risk factors) or age 80 years or older (with or without additional risk factors). The average age was 81 years.

Overall, participants were at intermediate to low risk from surgery, with a median Society of Thoracic Surgeons (STS) risk score of 2.6%. However, researchers did not specify a particular risk score cutoff for enrollment.

“This allowed the trial to evolve along with changes in guidelines and practice regarding TAVR over the course of the study and to reflect physicians’ nuanced, real-world approach to considering risk in decision-making rather than taking a formulaic approach,” Toff said.

At 1 year, the rate of death from any cause (the primary endpoint) was 4.6% in the TAVR group and 6.6% in the surgery group, a difference that met the trial’s prespecified threshold for noninferiority of TAVR.

Rates of death from cardiovascular disease or stroke were also similar between the two groups.

Patients who received TAVR had a significantly higher rate of vascular complications (4.8%) than those receiving surgery (1.3%).

TAVR patients were also more likely to have a pacemaker implanted. This occurred in 12.2% of TAVR patients and 6.6% of those undergoing surgery.

In addition, patients who underwent TAVR had a higher rate of aortic regurgitation. Mild aortic regurgitation occurred at 1 year in 38.3% of the TAVR group and 11.7% of the surgery group, whereas moderate regurgitation occurred in 2.3% of TAVR patients and 0.6% of surgery patients.

On the other hand, patients undergoing TAVR had a significantly lower rate of major bleeding complications, which occurred in 6.3% of patients having TAVR and 17.1% of those undergoing surgery.

TAVR was also associated with a shorter hospital stay, fewer days in intensive care, and a faster improvement in functional capacity and quality of life. Functional capacity and quality-of-life measures at 6 weeks after the procedure were better in the TAVR group but by 1 year they were similar in the two groups.

“Longer follow-up is required to confirm sustained clinical benefit and valve durability to inform clinical practice, particularly in younger patients,” Toff concluded.

“The results from our trial and others are encouraging, but patients need to be fully informed and know that the long-term durability of the TAVR valves and the long-term implications of the increased risk of aortic regurgitation are still uncertain,” he added.

The researchers plan to continue to track outcomes for a minimum of 5 years.

Discussant of the UK TAVI trial at an ACC press conference, Julia Grapsa, MD, Guys and St Thomas NHS Trust, London, United Kingdom, said it was a well-designed study.

“It was impressive to see so many UK sites and the age range of patients from 70 to 91 years, and the shorter hospital stays and functional recoveries as well as reduced major bleeding in the TAVR group,” Grapsa said.

“But something that was very striking to me was the increase in moderate aortic regurgitation in the TAVR arm, 2.3% versus 0.6% in the surgical arm, so it is very important to keep following these patients long term,” she added.

In answer to a question during the main session about using age alone as an inclusion criterion in those over 80 years old, Toff said, “We were more comfortable taking all comers over 80 years of age because of the uncertainty about TAVR is more in relation to its durability and the clinical significance of the aortic regurgitation, which may have consequences in the longer term. But the longer term for the over 80s is obviously less of a problem than for those in their 70s.”

This study was funded by the UK National Institute for Health Research Health Technology Assessment Programme. Toff reports no disclosures.

American College of Cardiology 2020 Scientific Session (ACC.20)/World Congress of Cardiology (WCC). Abstract 20-LB-20410-ACC. Presented March 29, 2020.

This article first appeared on Medscape.com.

Transcatheter aortic valve replacement (TAVR) was not inferior to conventional surgery with respect to death from any cause at 1 year in a new real-world study in patients age 70 years or older with severe symptomatic aortic stenosis at increased operative risk due to age or comorbidity.

The UK TAVI study was presented March 29 at the “virtual” American College of Cardiology 2020 Scientific Session (ACC.20)/World Congress of Cardiology (WCC).

The trial involved a broad group of patients who were treated at every medical center that performs the transcatheter procedure across the United Kingdom.

“The importance of this trial is that it confirms the effectiveness of the TAVR strategy in a real-world setting,” said lead author, William D. Toff, MD, professor of cardiology at the University of Leicester, United Kingdom.

Previous clinical trials have found TAVR to be noninferior or superior to open-heart surgery for various patient groups, but most trials have been limited to medical centers that perform a high volume of procedures or focus on the use of specific types of replacement valves, he noted.

“Our results are concordant with those from earlier trials in intermediate- and low-risk patients, but those earlier trials were performed in the best centers and had many exclusion criteria. We have replicated those results in populations more representative of the real world.”

“I think it is a very important message that supports the findings in earlier trials that were focused on showing whether TAVR can work under ideal conditions, while our trial shows that it does work in real-world clinical practice,” he added.

The UK TAVI trial enrolled 913 patients referred for treatment of severe aortic stenosis at 34 UK sites from 2014 to 2018. They were randomly assigned to receive TAVR or open-heart surgery.

Enrollment was limited to participants age 70 years or older (with additional risk factors) or age 80 years or older (with or without additional risk factors). The average age was 81 years.

Overall, participants were at intermediate to low risk from surgery, with a median Society of Thoracic Surgeons (STS) risk score of 2.6%. However, researchers did not specify a particular risk score cutoff for enrollment.

“This allowed the trial to evolve along with changes in guidelines and practice regarding TAVR over the course of the study and to reflect physicians’ nuanced, real-world approach to considering risk in decision-making rather than taking a formulaic approach,” Toff said.

At 1 year, the rate of death from any cause (the primary endpoint) was 4.6% in the TAVR group and 6.6% in the surgery group, a difference that met the trial’s prespecified threshold for noninferiority of TAVR.

Rates of death from cardiovascular disease or stroke were also similar between the two groups.

Patients who received TAVR had a significantly higher rate of vascular complications (4.8%) than those receiving surgery (1.3%).

TAVR patients were also more likely to have a pacemaker implanted. This occurred in 12.2% of TAVR patients and 6.6% of those undergoing surgery.

In addition, patients who underwent TAVR had a higher rate of aortic regurgitation. Mild aortic regurgitation occurred at 1 year in 38.3% of the TAVR group and 11.7% of the surgery group, whereas moderate regurgitation occurred in 2.3% of TAVR patients and 0.6% of surgery patients.

On the other hand, patients undergoing TAVR had a significantly lower rate of major bleeding complications, which occurred in 6.3% of patients having TAVR and 17.1% of those undergoing surgery.

TAVR was also associated with a shorter hospital stay, fewer days in intensive care, and a faster improvement in functional capacity and quality of life. Functional capacity and quality-of-life measures at 6 weeks after the procedure were better in the TAVR group but by 1 year they were similar in the two groups.

“Longer follow-up is required to confirm sustained clinical benefit and valve durability to inform clinical practice, particularly in younger patients,” Toff concluded.

“The results from our trial and others are encouraging, but patients need to be fully informed and know that the long-term durability of the TAVR valves and the long-term implications of the increased risk of aortic regurgitation are still uncertain,” he added.

The researchers plan to continue to track outcomes for a minimum of 5 years.

Discussant of the UK TAVI trial at an ACC press conference, Julia Grapsa, MD, Guys and St Thomas NHS Trust, London, United Kingdom, said it was a well-designed study.

“It was impressive to see so many UK sites and the age range of patients from 70 to 91 years, and the shorter hospital stays and functional recoveries as well as reduced major bleeding in the TAVR group,” Grapsa said.

“But something that was very striking to me was the increase in moderate aortic regurgitation in the TAVR arm, 2.3% versus 0.6% in the surgical arm, so it is very important to keep following these patients long term,” she added.

In answer to a question during the main session about using age alone as an inclusion criterion in those over 80 years old, Toff said, “We were more comfortable taking all comers over 80 years of age because of the uncertainty about TAVR is more in relation to its durability and the clinical significance of the aortic regurgitation, which may have consequences in the longer term. But the longer term for the over 80s is obviously less of a problem than for those in their 70s.”

This study was funded by the UK National Institute for Health Research Health Technology Assessment Programme. Toff reports no disclosures.

American College of Cardiology 2020 Scientific Session (ACC.20)/World Congress of Cardiology (WCC). Abstract 20-LB-20410-ACC. Presented March 29, 2020.

This article first appeared on Medscape.com.

Transcatheter aortic valve replacement (TAVR) was not inferior to conventional surgery with respect to death from any cause at 1 year in a new real-world study in patients age 70 years or older with severe symptomatic aortic stenosis at increased operative risk due to age or comorbidity.

The UK TAVI study was presented March 29 at the “virtual” American College of Cardiology 2020 Scientific Session (ACC.20)/World Congress of Cardiology (WCC).

The trial involved a broad group of patients who were treated at every medical center that performs the transcatheter procedure across the United Kingdom.

“The importance of this trial is that it confirms the effectiveness of the TAVR strategy in a real-world setting,” said lead author, William D. Toff, MD, professor of cardiology at the University of Leicester, United Kingdom.

Previous clinical trials have found TAVR to be noninferior or superior to open-heart surgery for various patient groups, but most trials have been limited to medical centers that perform a high volume of procedures or focus on the use of specific types of replacement valves, he noted.

“Our results are concordant with those from earlier trials in intermediate- and low-risk patients, but those earlier trials were performed in the best centers and had many exclusion criteria. We have replicated those results in populations more representative of the real world.”

“I think it is a very important message that supports the findings in earlier trials that were focused on showing whether TAVR can work under ideal conditions, while our trial shows that it does work in real-world clinical practice,” he added.

The UK TAVI trial enrolled 913 patients referred for treatment of severe aortic stenosis at 34 UK sites from 2014 to 2018. They were randomly assigned to receive TAVR or open-heart surgery.

Enrollment was limited to participants age 70 years or older (with additional risk factors) or age 80 years or older (with or without additional risk factors). The average age was 81 years.

Overall, participants were at intermediate to low risk from surgery, with a median Society of Thoracic Surgeons (STS) risk score of 2.6%. However, researchers did not specify a particular risk score cutoff for enrollment.

“This allowed the trial to evolve along with changes in guidelines and practice regarding TAVR over the course of the study and to reflect physicians’ nuanced, real-world approach to considering risk in decision-making rather than taking a formulaic approach,” Toff said.

At 1 year, the rate of death from any cause (the primary endpoint) was 4.6% in the TAVR group and 6.6% in the surgery group, a difference that met the trial’s prespecified threshold for noninferiority of TAVR.

Rates of death from cardiovascular disease or stroke were also similar between the two groups.

Patients who received TAVR had a significantly higher rate of vascular complications (4.8%) than those receiving surgery (1.3%).

TAVR patients were also more likely to have a pacemaker implanted. This occurred in 12.2% of TAVR patients and 6.6% of those undergoing surgery.

In addition, patients who underwent TAVR had a higher rate of aortic regurgitation. Mild aortic regurgitation occurred at 1 year in 38.3% of the TAVR group and 11.7% of the surgery group, whereas moderate regurgitation occurred in 2.3% of TAVR patients and 0.6% of surgery patients.

On the other hand, patients undergoing TAVR had a significantly lower rate of major bleeding complications, which occurred in 6.3% of patients having TAVR and 17.1% of those undergoing surgery.

TAVR was also associated with a shorter hospital stay, fewer days in intensive care, and a faster improvement in functional capacity and quality of life. Functional capacity and quality-of-life measures at 6 weeks after the procedure were better in the TAVR group but by 1 year they were similar in the two groups.

“Longer follow-up is required to confirm sustained clinical benefit and valve durability to inform clinical practice, particularly in younger patients,” Toff concluded.

“The results from our trial and others are encouraging, but patients need to be fully informed and know that the long-term durability of the TAVR valves and the long-term implications of the increased risk of aortic regurgitation are still uncertain,” he added.

The researchers plan to continue to track outcomes for a minimum of 5 years.

Discussant of the UK TAVI trial at an ACC press conference, Julia Grapsa, MD, Guys and St Thomas NHS Trust, London, United Kingdom, said it was a well-designed study.

“It was impressive to see so many UK sites and the age range of patients from 70 to 91 years, and the shorter hospital stays and functional recoveries as well as reduced major bleeding in the TAVR group,” Grapsa said.

“But something that was very striking to me was the increase in moderate aortic regurgitation in the TAVR arm, 2.3% versus 0.6% in the surgical arm, so it is very important to keep following these patients long term,” she added.

In answer to a question during the main session about using age alone as an inclusion criterion in those over 80 years old, Toff said, “We were more comfortable taking all comers over 80 years of age because of the uncertainty about TAVR is more in relation to its durability and the clinical significance of the aortic regurgitation, which may have consequences in the longer term. But the longer term for the over 80s is obviously less of a problem than for those in their 70s.”

This study was funded by the UK National Institute for Health Research Health Technology Assessment Programme. Toff reports no disclosures.

American College of Cardiology 2020 Scientific Session (ACC.20)/World Congress of Cardiology (WCC). Abstract 20-LB-20410-ACC. Presented March 29, 2020.

This article first appeared on Medscape.com.