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Mitchel is a reporter for MDedge based in the Philadelphia area. He started with the company in 1992, when it was International Medical News Group (IMNG), and has since covered a range of medical specialties. Mitchel trained as a virologist at Roswell Park Memorial Institute in Buffalo, and then worked briefly as a researcher at Boston Children's Hospital before pivoting to journalism as a AAAS Mass Media Fellow in 1980. His first reporting job was with Science Digest magazine, and from the mid-1980s to early-1990s he was a reporter with Medical World News. @mitchelzoler
Expanded drug combinations produce best myeloma induction
NEW YORK – Optimal induction therapy for patients with multiple myeloma requires all the therapeutic tools currently available for combination therapy, which means using four agents followed by autologous stem cell transplantation, Paul G. Richardson, MD, said at a conference held by Imedex.
He suggested that a rational combination regimen for induction therapy of multiple myeloma would include a second- or third-generation immunomodulator such as lenalidomide (Revlimid) or pomalidomide (Pomalyst); a proteasome inhibitor such as bortezomib (Velcade), carfilzomib (Kyprolis), or ixazomib (Ninlaro); plus standard dexamethasone to form a contemporary backbone regimen for inducing remission in patients with multiple myeloma.
“Therapeutic parsimony is not recommended. You need a combination” of all available drug classes, suggested Dr. Richardson, professor of medicine at Harvard Medical School and clinical program leader of the Multiple Myeloma Center at the Dana-Farber Cancer Institute in Boston.
“It isn’t rational to limit the treatment choices. We need to bring them all together,” he said. The “most rational” combination melds an immunomodulator, proteasome inhibitor, plus a monoclonal antibody that he called a “true game changer. Add the antibody on top of the three-drug platform” of an immunomodulator, proteasome inhibitor, and dexamethasone. Dr. Richardson conceded, however, that a concern with such combinations is how to manage the toxicity that would likely result.
He cited several recent examples of demonstrated superior efficacy in the form of more complete responses from combined regimens, followed by autologous stem cell transplantation.
For example, a recent report from a French-led group compared the efficacy of a combination of an immunomodulator, proteasome inhibitor, and dexamethasone against the same combination, followed by autologous stem cell transplantation (N Engl J Med. 2017 Apr 6;376[14]:1311-20). The combined regimen plus transplant resulted in a 59% complete response rate, “the best response rate we’ve ever seen” in multiple myeloma, Dr. Richardson noted, compared with a 48% complete response rate in patients who did not undergo a stem cell transplant.
Another speaker at the meeting, Ruben Niesvizky, MD, suggested a more cautious approach to using the monoclonal antibody daratumumab for induction. He cited the published experience in adding the antibody to pared-down backbone therapy in the setting of relapsed or relapsed and refractory disease, such as a proteasome inhibitor plus dexamethasone (N Engl J Med. 2016 Aug 25;375[8]:754-66) or an immunomodulator plus dexamethasone (N Engl J Med. 2016 Oct 6;375[14]:1319-31).
Adding a monoclonal antibody such as daratumumab to combination therapy is the “wave of the future,” said Dr. Niesvizky, professor of medicine and director of the Multiple Myeloma Center at New York Presbyterian Hospital/Weill Cornell Medical Center. It provides treatment that reduces disease-related complications and achieves effective and extended disease control with improved overall survival, while being well tolerated and facilitating stem cell collection.
Dr. Richardson has been a consultant to Celgene, Genmab, Janssen, Novartis, Oncopeptides AB, and Takeda and has received research funding from Celgene and Takeda. Dr. Niesvizky has been a consultant to Amgen, Bristol-Myers Squibb, Celgene, Janssen, and Takeda and has received research support from Amgen, Bristol-Myers Squibb, Celgene, and Takeda.
mzoler@frontlinemedcom.com
On Twitter @mitchelzoler
NEW YORK – Optimal induction therapy for patients with multiple myeloma requires all the therapeutic tools currently available for combination therapy, which means using four agents followed by autologous stem cell transplantation, Paul G. Richardson, MD, said at a conference held by Imedex.
He suggested that a rational combination regimen for induction therapy of multiple myeloma would include a second- or third-generation immunomodulator such as lenalidomide (Revlimid) or pomalidomide (Pomalyst); a proteasome inhibitor such as bortezomib (Velcade), carfilzomib (Kyprolis), or ixazomib (Ninlaro); plus standard dexamethasone to form a contemporary backbone regimen for inducing remission in patients with multiple myeloma.
“Therapeutic parsimony is not recommended. You need a combination” of all available drug classes, suggested Dr. Richardson, professor of medicine at Harvard Medical School and clinical program leader of the Multiple Myeloma Center at the Dana-Farber Cancer Institute in Boston.
“It isn’t rational to limit the treatment choices. We need to bring them all together,” he said. The “most rational” combination melds an immunomodulator, proteasome inhibitor, plus a monoclonal antibody that he called a “true game changer. Add the antibody on top of the three-drug platform” of an immunomodulator, proteasome inhibitor, and dexamethasone. Dr. Richardson conceded, however, that a concern with such combinations is how to manage the toxicity that would likely result.
He cited several recent examples of demonstrated superior efficacy in the form of more complete responses from combined regimens, followed by autologous stem cell transplantation.
For example, a recent report from a French-led group compared the efficacy of a combination of an immunomodulator, proteasome inhibitor, and dexamethasone against the same combination, followed by autologous stem cell transplantation (N Engl J Med. 2017 Apr 6;376[14]:1311-20). The combined regimen plus transplant resulted in a 59% complete response rate, “the best response rate we’ve ever seen” in multiple myeloma, Dr. Richardson noted, compared with a 48% complete response rate in patients who did not undergo a stem cell transplant.
Another speaker at the meeting, Ruben Niesvizky, MD, suggested a more cautious approach to using the monoclonal antibody daratumumab for induction. He cited the published experience in adding the antibody to pared-down backbone therapy in the setting of relapsed or relapsed and refractory disease, such as a proteasome inhibitor plus dexamethasone (N Engl J Med. 2016 Aug 25;375[8]:754-66) or an immunomodulator plus dexamethasone (N Engl J Med. 2016 Oct 6;375[14]:1319-31).
Adding a monoclonal antibody such as daratumumab to combination therapy is the “wave of the future,” said Dr. Niesvizky, professor of medicine and director of the Multiple Myeloma Center at New York Presbyterian Hospital/Weill Cornell Medical Center. It provides treatment that reduces disease-related complications and achieves effective and extended disease control with improved overall survival, while being well tolerated and facilitating stem cell collection.
Dr. Richardson has been a consultant to Celgene, Genmab, Janssen, Novartis, Oncopeptides AB, and Takeda and has received research funding from Celgene and Takeda. Dr. Niesvizky has been a consultant to Amgen, Bristol-Myers Squibb, Celgene, Janssen, and Takeda and has received research support from Amgen, Bristol-Myers Squibb, Celgene, and Takeda.
mzoler@frontlinemedcom.com
On Twitter @mitchelzoler
NEW YORK – Optimal induction therapy for patients with multiple myeloma requires all the therapeutic tools currently available for combination therapy, which means using four agents followed by autologous stem cell transplantation, Paul G. Richardson, MD, said at a conference held by Imedex.
He suggested that a rational combination regimen for induction therapy of multiple myeloma would include a second- or third-generation immunomodulator such as lenalidomide (Revlimid) or pomalidomide (Pomalyst); a proteasome inhibitor such as bortezomib (Velcade), carfilzomib (Kyprolis), or ixazomib (Ninlaro); plus standard dexamethasone to form a contemporary backbone regimen for inducing remission in patients with multiple myeloma.
“Therapeutic parsimony is not recommended. You need a combination” of all available drug classes, suggested Dr. Richardson, professor of medicine at Harvard Medical School and clinical program leader of the Multiple Myeloma Center at the Dana-Farber Cancer Institute in Boston.
“It isn’t rational to limit the treatment choices. We need to bring them all together,” he said. The “most rational” combination melds an immunomodulator, proteasome inhibitor, plus a monoclonal antibody that he called a “true game changer. Add the antibody on top of the three-drug platform” of an immunomodulator, proteasome inhibitor, and dexamethasone. Dr. Richardson conceded, however, that a concern with such combinations is how to manage the toxicity that would likely result.
He cited several recent examples of demonstrated superior efficacy in the form of more complete responses from combined regimens, followed by autologous stem cell transplantation.
For example, a recent report from a French-led group compared the efficacy of a combination of an immunomodulator, proteasome inhibitor, and dexamethasone against the same combination, followed by autologous stem cell transplantation (N Engl J Med. 2017 Apr 6;376[14]:1311-20). The combined regimen plus transplant resulted in a 59% complete response rate, “the best response rate we’ve ever seen” in multiple myeloma, Dr. Richardson noted, compared with a 48% complete response rate in patients who did not undergo a stem cell transplant.
Another speaker at the meeting, Ruben Niesvizky, MD, suggested a more cautious approach to using the monoclonal antibody daratumumab for induction. He cited the published experience in adding the antibody to pared-down backbone therapy in the setting of relapsed or relapsed and refractory disease, such as a proteasome inhibitor plus dexamethasone (N Engl J Med. 2016 Aug 25;375[8]:754-66) or an immunomodulator plus dexamethasone (N Engl J Med. 2016 Oct 6;375[14]:1319-31).
Adding a monoclonal antibody such as daratumumab to combination therapy is the “wave of the future,” said Dr. Niesvizky, professor of medicine and director of the Multiple Myeloma Center at New York Presbyterian Hospital/Weill Cornell Medical Center. It provides treatment that reduces disease-related complications and achieves effective and extended disease control with improved overall survival, while being well tolerated and facilitating stem cell collection.
Dr. Richardson has been a consultant to Celgene, Genmab, Janssen, Novartis, Oncopeptides AB, and Takeda and has received research funding from Celgene and Takeda. Dr. Niesvizky has been a consultant to Amgen, Bristol-Myers Squibb, Celgene, Janssen, and Takeda and has received research support from Amgen, Bristol-Myers Squibb, Celgene, and Takeda.
mzoler@frontlinemedcom.com
On Twitter @mitchelzoler
EXPERT ANALYSIS FROM A MEETING ON HEMATOLOGIC MALIGNANCIES
Coverage denials plague U.S. PCSK9-inhibitor prescriptions
WASHINGTON – During the first year that the lipid-lowering PCSK9 inhibitors were on the U.S. market, 2015-2016, fewer than half the patients prescribed the drug had it covered through their health insurance, based on an analysis of prescriptions written for more than 45,000 patients.
On top of that, about a third of patients with health insurance that eventually agreed to cover the notoriously expensive PCSK (proprotein convertase subtilisin–kexin type) 9 inhibitors failed to actually collect their medication, possibly because of a sizable copay, which meant that, in total, fewer than a third of U.S. patients prescribed these drugs actually began using them, Ann Marie Navar, MD, said at the annual meeting of the American College of Cardiology.
The recent PCSK9-inhibitor experience highlighting the frequent preauthorization roadblocks and denied coverage that providers and patients must navigate is “one of the dirty little secrets of American medicine,” commented Mariell Jessup, MD, a discussant for the study and professor of medicine at the University of Pennsylvania in Philadelphia.
Dr. Navar countered that these problems may be a secret for many Americans “but it’s not a secret for providers. We know the problems patients have getting drugs covered through the prior authorization process.”
Symphony Health’s records included 45,029 U.S. patients who received a first-time PCSK9-inhibitor prescription during the 12 months studied. Just over half were prescriptions exclusively covered by government-funded insurance (with 90% of these covered through Medicaid), 40% exclusively by a commercial insurer, and the balance subject to dual coverage. Nearly half the prescriptions were written by cardiologists, 37% by primary care physicians, and most of the remaining 15% came from endocrinologists.
Among these prescriptions, 79% received an initial rejection. Following appeals, 53% were rejected and 47% covered. Among the more than 21,000 prescriptions approved for coverage, 13,892 (31% of the 45,029) were actually received by patients, Dr. Navar reported.
During the first several months following availability of the PCSK9 inhibitors, the number of new prescriptions steadily rose until a plateau occurred by about April 2016 of about 6,000 new prescriptions written per month. During each of the 12 months examined, the proportion of prescriptions denied coverage remained roughly constant, suggesting that clinicians developed no insights over time into how to better the prospect for ultimate insurance coverage.
In a multivariate analysis certain aspects of the prescribing and coverage process linked with significantly better rates of patients actually receiving the PCSK9 inhibitor. Prescriptions filled at mail-order pharmacies were over fourfold more likely to be received by patients than those filled at retail pharmacies. Prescriptions written by cardiologists were 80% more likely to be received than those written by primary care physicians; those written by endocrinologists were 30% more likely to be filled. Patients who relied exclusively on a government insurance plan had a threefold greater filling rate than those who exclusively had commercial insurance, and patients with both government and commercial insurance had a fourfold greater rate of receiving their prescription, compared with commercial-only patients. Patients who used a manufacturer’s coupon to help reduce the cost of their prescription had a 17-fold higher rate of receiving the drug, compared with patients who did not use a coupon.
A final set of findings underscored the great variability in the approval process that patients encountered. Among the 13,892 prescriptions that were actually dispensed, 45% were dispensed within 1 day of when the prescription was written, but the median time for dispensing wasn’t reached until the tenth day, and for a quarter of the dispenses the lag from writing the prescription to getting it into patients’ hands was greater than 1 month. Rates of coverage denials also varied widely depending on the specific commercial insurers involved and the specific pharmacy benefit manager. Among the top 10 commercial insurers included in the data set, the rate of coverage denial ranged from 33% to 78%.
This variability suggested that many denials were not simply because of clinical factors. Some commercial insurers “introduce vigorous and sometimes burdensome prior authorization procedures,” Dr. Navar said.
mzoler@frontlinemedcom.com
On Twitter @mitchelzoler
WASHINGTON – During the first year that the lipid-lowering PCSK9 inhibitors were on the U.S. market, 2015-2016, fewer than half the patients prescribed the drug had it covered through their health insurance, based on an analysis of prescriptions written for more than 45,000 patients.
On top of that, about a third of patients with health insurance that eventually agreed to cover the notoriously expensive PCSK (proprotein convertase subtilisin–kexin type) 9 inhibitors failed to actually collect their medication, possibly because of a sizable copay, which meant that, in total, fewer than a third of U.S. patients prescribed these drugs actually began using them, Ann Marie Navar, MD, said at the annual meeting of the American College of Cardiology.
The recent PCSK9-inhibitor experience highlighting the frequent preauthorization roadblocks and denied coverage that providers and patients must navigate is “one of the dirty little secrets of American medicine,” commented Mariell Jessup, MD, a discussant for the study and professor of medicine at the University of Pennsylvania in Philadelphia.
Dr. Navar countered that these problems may be a secret for many Americans “but it’s not a secret for providers. We know the problems patients have getting drugs covered through the prior authorization process.”
Symphony Health’s records included 45,029 U.S. patients who received a first-time PCSK9-inhibitor prescription during the 12 months studied. Just over half were prescriptions exclusively covered by government-funded insurance (with 90% of these covered through Medicaid), 40% exclusively by a commercial insurer, and the balance subject to dual coverage. Nearly half the prescriptions were written by cardiologists, 37% by primary care physicians, and most of the remaining 15% came from endocrinologists.
Among these prescriptions, 79% received an initial rejection. Following appeals, 53% were rejected and 47% covered. Among the more than 21,000 prescriptions approved for coverage, 13,892 (31% of the 45,029) were actually received by patients, Dr. Navar reported.
During the first several months following availability of the PCSK9 inhibitors, the number of new prescriptions steadily rose until a plateau occurred by about April 2016 of about 6,000 new prescriptions written per month. During each of the 12 months examined, the proportion of prescriptions denied coverage remained roughly constant, suggesting that clinicians developed no insights over time into how to better the prospect for ultimate insurance coverage.
In a multivariate analysis certain aspects of the prescribing and coverage process linked with significantly better rates of patients actually receiving the PCSK9 inhibitor. Prescriptions filled at mail-order pharmacies were over fourfold more likely to be received by patients than those filled at retail pharmacies. Prescriptions written by cardiologists were 80% more likely to be received than those written by primary care physicians; those written by endocrinologists were 30% more likely to be filled. Patients who relied exclusively on a government insurance plan had a threefold greater filling rate than those who exclusively had commercial insurance, and patients with both government and commercial insurance had a fourfold greater rate of receiving their prescription, compared with commercial-only patients. Patients who used a manufacturer’s coupon to help reduce the cost of their prescription had a 17-fold higher rate of receiving the drug, compared with patients who did not use a coupon.
A final set of findings underscored the great variability in the approval process that patients encountered. Among the 13,892 prescriptions that were actually dispensed, 45% were dispensed within 1 day of when the prescription was written, but the median time for dispensing wasn’t reached until the tenth day, and for a quarter of the dispenses the lag from writing the prescription to getting it into patients’ hands was greater than 1 month. Rates of coverage denials also varied widely depending on the specific commercial insurers involved and the specific pharmacy benefit manager. Among the top 10 commercial insurers included in the data set, the rate of coverage denial ranged from 33% to 78%.
This variability suggested that many denials were not simply because of clinical factors. Some commercial insurers “introduce vigorous and sometimes burdensome prior authorization procedures,” Dr. Navar said.
mzoler@frontlinemedcom.com
On Twitter @mitchelzoler
WASHINGTON – During the first year that the lipid-lowering PCSK9 inhibitors were on the U.S. market, 2015-2016, fewer than half the patients prescribed the drug had it covered through their health insurance, based on an analysis of prescriptions written for more than 45,000 patients.
On top of that, about a third of patients with health insurance that eventually agreed to cover the notoriously expensive PCSK (proprotein convertase subtilisin–kexin type) 9 inhibitors failed to actually collect their medication, possibly because of a sizable copay, which meant that, in total, fewer than a third of U.S. patients prescribed these drugs actually began using them, Ann Marie Navar, MD, said at the annual meeting of the American College of Cardiology.
The recent PCSK9-inhibitor experience highlighting the frequent preauthorization roadblocks and denied coverage that providers and patients must navigate is “one of the dirty little secrets of American medicine,” commented Mariell Jessup, MD, a discussant for the study and professor of medicine at the University of Pennsylvania in Philadelphia.
Dr. Navar countered that these problems may be a secret for many Americans “but it’s not a secret for providers. We know the problems patients have getting drugs covered through the prior authorization process.”
Symphony Health’s records included 45,029 U.S. patients who received a first-time PCSK9-inhibitor prescription during the 12 months studied. Just over half were prescriptions exclusively covered by government-funded insurance (with 90% of these covered through Medicaid), 40% exclusively by a commercial insurer, and the balance subject to dual coverage. Nearly half the prescriptions were written by cardiologists, 37% by primary care physicians, and most of the remaining 15% came from endocrinologists.
Among these prescriptions, 79% received an initial rejection. Following appeals, 53% were rejected and 47% covered. Among the more than 21,000 prescriptions approved for coverage, 13,892 (31% of the 45,029) were actually received by patients, Dr. Navar reported.
During the first several months following availability of the PCSK9 inhibitors, the number of new prescriptions steadily rose until a plateau occurred by about April 2016 of about 6,000 new prescriptions written per month. During each of the 12 months examined, the proportion of prescriptions denied coverage remained roughly constant, suggesting that clinicians developed no insights over time into how to better the prospect for ultimate insurance coverage.
In a multivariate analysis certain aspects of the prescribing and coverage process linked with significantly better rates of patients actually receiving the PCSK9 inhibitor. Prescriptions filled at mail-order pharmacies were over fourfold more likely to be received by patients than those filled at retail pharmacies. Prescriptions written by cardiologists were 80% more likely to be received than those written by primary care physicians; those written by endocrinologists were 30% more likely to be filled. Patients who relied exclusively on a government insurance plan had a threefold greater filling rate than those who exclusively had commercial insurance, and patients with both government and commercial insurance had a fourfold greater rate of receiving their prescription, compared with commercial-only patients. Patients who used a manufacturer’s coupon to help reduce the cost of their prescription had a 17-fold higher rate of receiving the drug, compared with patients who did not use a coupon.
A final set of findings underscored the great variability in the approval process that patients encountered. Among the 13,892 prescriptions that were actually dispensed, 45% were dispensed within 1 day of when the prescription was written, but the median time for dispensing wasn’t reached until the tenth day, and for a quarter of the dispenses the lag from writing the prescription to getting it into patients’ hands was greater than 1 month. Rates of coverage denials also varied widely depending on the specific commercial insurers involved and the specific pharmacy benefit manager. Among the top 10 commercial insurers included in the data set, the rate of coverage denial ranged from 33% to 78%.
This variability suggested that many denials were not simply because of clinical factors. Some commercial insurers “introduce vigorous and sometimes burdensome prior authorization procedures,” Dr. Navar said.
mzoler@frontlinemedcom.com
On Twitter @mitchelzoler
AT ACC 17
Key clinical point:
Major finding: Coverage denials occurred for 53% of U.S. patients who received a new prescription for a PCSK9 inhibitor during 2015-2016.
Data source: Review of 45,029 U.S. patients who received a new prescription for a PCSK9 inhibitor in a Symphony Health database.
Disclosures: The study was sponsored by Amgen, the company that markets evolocumab (Repatha). Dr. Navar has received research support from Amgen, Sanofi, and Regeneron and has been a consultant to Sanofi.
Death watch intensifies for HDL-based interventions
WASHINGTON – Is it finally time to give up on HDL cholesterol–based interventions to treat atherosclerotic disease?
The approach “is on life support,” admitted Stephen J. Nicholls, MD, a long-time leader in the field who has reported results from a series of studies during the past 10 or so years that tested various approaches to juicing HDL cholesterol activity in patients, only to see each and every candidate intervention result in an inability to budge clinical outcomes.
The latest disappointment he reported was for CER-001, an engineered HDL mimetic agent. In a placebo-controlled international study, CARAT (CER-001 Atherosclerosis Regression ACS Trial), with 301 randomized patients and 272 completers, 10 weekly infusions of CER-001 over the course of 9 weeks failed to produce discernible incremental regression of atherosclerotic plaque volume, compared with standard care measured by serial examination using intravascular ultrasound (IVUS), Dr. Nicholls reported. The absence of any detectable benefit “suggests that this is not a promising strategy,” he said during his report at the meeting.
Enthusiasm for HDL cholesterol–based interventions dates to 2003, when an IVUS study of a first-generation HDL mimetic agent, ETC-216, showed an apparent ability to produce regression of coronary atheroma after five infusions over a 2-week period, compared with placebo-treated patients (JAMA. 2003 Nov 5;290[17]:2292-300). But the successor compound to this agent, MDCO-216, flamed out in an IVUS study with 113 completing patients that Dr. Nicholls reported at the American Heart Association Scientific Sessions in November 2016.
Also lying dead on the trial trail during past years are several cholesterol ester transfer protein inhibitors – torcetrapib, dalcetrapib and evacetrapib – as well as other agents that Dr. Nicholls described in a recent review (Arch Med Sci. 2016 Oct 24;12[6]:1302-7).
“HDL wouldn’t be the first risk factor we’ve seen that is not a modifiable target. Homocysteine is a really good example” of another atherosclerotic disease risk that’s proven immune to intervention, Dr. Nicholls said in an interview at the meeting. “Ultimately we’ll come to a point when the enthusiasm [for potential HDL interventions] will wane, but we’re not quite there yet.”
“There are other players in the HDL field” that remain viable, said Dr. Nicholls, most notably CSL112, plasma-derived apoA1 – the primary functional part of HDL cholesterol – that’s infused into patients to boost HDL activity. Results from a phase II study reported in November 2016 showed it increased cholesterol efflux (Circulation 2016 Nov; doi: 10.1161/CIRCULATIONAHA.116.025687), and is now the subject of additional phase II testing. “But with every negative trial, it will get harder and harder [to fund new HDL research], and we’ll look for other targets,” he said.
One promising alternative target is triglycerides. “HDL has received more attention than triglycerides over the past decade, but I think that will start to change as HDL can’t deliver,” predicted Dr. Nicholls, professor of cardiology at the South Australian Health & Medical Research Institute in Adelaide.
Understandably “financial support is the biggest issue. Do companies and investors still believe in the [HDL] dream?” Dr. Nicholls said that, objectively, looking at the HDL research record should definitely give investors pause before they sink money into new compounds for HDL intervention.
“If I was sitting at the drawing board now, would HDL be the risk factor I’d target? Probably not,” he concluded.
Dr. Nicholls received research support from Cerenis, the company that is developing CER-001, and he has received honoraria and research support from several other companies. Dr. Bhatt has received research support from several drug companies.
mzoler@frontlinemedcom.com
On Twitter @mitchelzoler
WASHINGTON – Is it finally time to give up on HDL cholesterol–based interventions to treat atherosclerotic disease?
The approach “is on life support,” admitted Stephen J. Nicholls, MD, a long-time leader in the field who has reported results from a series of studies during the past 10 or so years that tested various approaches to juicing HDL cholesterol activity in patients, only to see each and every candidate intervention result in an inability to budge clinical outcomes.
The latest disappointment he reported was for CER-001, an engineered HDL mimetic agent. In a placebo-controlled international study, CARAT (CER-001 Atherosclerosis Regression ACS Trial), with 301 randomized patients and 272 completers, 10 weekly infusions of CER-001 over the course of 9 weeks failed to produce discernible incremental regression of atherosclerotic plaque volume, compared with standard care measured by serial examination using intravascular ultrasound (IVUS), Dr. Nicholls reported. The absence of any detectable benefit “suggests that this is not a promising strategy,” he said during his report at the meeting.
Enthusiasm for HDL cholesterol–based interventions dates to 2003, when an IVUS study of a first-generation HDL mimetic agent, ETC-216, showed an apparent ability to produce regression of coronary atheroma after five infusions over a 2-week period, compared with placebo-treated patients (JAMA. 2003 Nov 5;290[17]:2292-300). But the successor compound to this agent, MDCO-216, flamed out in an IVUS study with 113 completing patients that Dr. Nicholls reported at the American Heart Association Scientific Sessions in November 2016.
Also lying dead on the trial trail during past years are several cholesterol ester transfer protein inhibitors – torcetrapib, dalcetrapib and evacetrapib – as well as other agents that Dr. Nicholls described in a recent review (Arch Med Sci. 2016 Oct 24;12[6]:1302-7).
“HDL wouldn’t be the first risk factor we’ve seen that is not a modifiable target. Homocysteine is a really good example” of another atherosclerotic disease risk that’s proven immune to intervention, Dr. Nicholls said in an interview at the meeting. “Ultimately we’ll come to a point when the enthusiasm [for potential HDL interventions] will wane, but we’re not quite there yet.”
“There are other players in the HDL field” that remain viable, said Dr. Nicholls, most notably CSL112, plasma-derived apoA1 – the primary functional part of HDL cholesterol – that’s infused into patients to boost HDL activity. Results from a phase II study reported in November 2016 showed it increased cholesterol efflux (Circulation 2016 Nov; doi: 10.1161/CIRCULATIONAHA.116.025687), and is now the subject of additional phase II testing. “But with every negative trial, it will get harder and harder [to fund new HDL research], and we’ll look for other targets,” he said.
One promising alternative target is triglycerides. “HDL has received more attention than triglycerides over the past decade, but I think that will start to change as HDL can’t deliver,” predicted Dr. Nicholls, professor of cardiology at the South Australian Health & Medical Research Institute in Adelaide.
Understandably “financial support is the biggest issue. Do companies and investors still believe in the [HDL] dream?” Dr. Nicholls said that, objectively, looking at the HDL research record should definitely give investors pause before they sink money into new compounds for HDL intervention.
“If I was sitting at the drawing board now, would HDL be the risk factor I’d target? Probably not,” he concluded.
Dr. Nicholls received research support from Cerenis, the company that is developing CER-001, and he has received honoraria and research support from several other companies. Dr. Bhatt has received research support from several drug companies.
mzoler@frontlinemedcom.com
On Twitter @mitchelzoler
WASHINGTON – Is it finally time to give up on HDL cholesterol–based interventions to treat atherosclerotic disease?
The approach “is on life support,” admitted Stephen J. Nicholls, MD, a long-time leader in the field who has reported results from a series of studies during the past 10 or so years that tested various approaches to juicing HDL cholesterol activity in patients, only to see each and every candidate intervention result in an inability to budge clinical outcomes.
The latest disappointment he reported was for CER-001, an engineered HDL mimetic agent. In a placebo-controlled international study, CARAT (CER-001 Atherosclerosis Regression ACS Trial), with 301 randomized patients and 272 completers, 10 weekly infusions of CER-001 over the course of 9 weeks failed to produce discernible incremental regression of atherosclerotic plaque volume, compared with standard care measured by serial examination using intravascular ultrasound (IVUS), Dr. Nicholls reported. The absence of any detectable benefit “suggests that this is not a promising strategy,” he said during his report at the meeting.
Enthusiasm for HDL cholesterol–based interventions dates to 2003, when an IVUS study of a first-generation HDL mimetic agent, ETC-216, showed an apparent ability to produce regression of coronary atheroma after five infusions over a 2-week period, compared with placebo-treated patients (JAMA. 2003 Nov 5;290[17]:2292-300). But the successor compound to this agent, MDCO-216, flamed out in an IVUS study with 113 completing patients that Dr. Nicholls reported at the American Heart Association Scientific Sessions in November 2016.
Also lying dead on the trial trail during past years are several cholesterol ester transfer protein inhibitors – torcetrapib, dalcetrapib and evacetrapib – as well as other agents that Dr. Nicholls described in a recent review (Arch Med Sci. 2016 Oct 24;12[6]:1302-7).
“HDL wouldn’t be the first risk factor we’ve seen that is not a modifiable target. Homocysteine is a really good example” of another atherosclerotic disease risk that’s proven immune to intervention, Dr. Nicholls said in an interview at the meeting. “Ultimately we’ll come to a point when the enthusiasm [for potential HDL interventions] will wane, but we’re not quite there yet.”
“There are other players in the HDL field” that remain viable, said Dr. Nicholls, most notably CSL112, plasma-derived apoA1 – the primary functional part of HDL cholesterol – that’s infused into patients to boost HDL activity. Results from a phase II study reported in November 2016 showed it increased cholesterol efflux (Circulation 2016 Nov; doi: 10.1161/CIRCULATIONAHA.116.025687), and is now the subject of additional phase II testing. “But with every negative trial, it will get harder and harder [to fund new HDL research], and we’ll look for other targets,” he said.
One promising alternative target is triglycerides. “HDL has received more attention than triglycerides over the past decade, but I think that will start to change as HDL can’t deliver,” predicted Dr. Nicholls, professor of cardiology at the South Australian Health & Medical Research Institute in Adelaide.
Understandably “financial support is the biggest issue. Do companies and investors still believe in the [HDL] dream?” Dr. Nicholls said that, objectively, looking at the HDL research record should definitely give investors pause before they sink money into new compounds for HDL intervention.
“If I was sitting at the drawing board now, would HDL be the risk factor I’d target? Probably not,” he concluded.
Dr. Nicholls received research support from Cerenis, the company that is developing CER-001, and he has received honoraria and research support from several other companies. Dr. Bhatt has received research support from several drug companies.
mzoler@frontlinemedcom.com
On Twitter @mitchelzoler
EXPERT ANALYSIS FROM ACC 17
VIDEO: Blinatumomab, inotuzumab reshape relapsed ALL treatment
NEW YORK – A pair of new monoclonal antibodies have dramatically changed treatment for patients with acute lymphoblastic leukemia to prepare them for a stem cell transplant, Daniel J. DeAngelo, MD, said at a conference held by Imedex.
“We don’t use standard chemotherapy for reinduction anymore; we use blinatumomab or inotuzumab,” said Dr. DeAngelo, a hematologist oncologist at Dana-Farber Cancer Institute in Boston.
Blinatumomab (Blincyto), approved by the Food and Drug Administration in 2014, has produced “exceptional” response rates, becoming “standard of care” for patients with relapsed acute lymphoblastic leukemia (ALL) that does not have a Philadelphia chromosome, Dr. DeAngelo said in a video interview.
Approved based on results from a phase II study, blinatumomab’s efficacy and safety were recently further delineated in results from the first phase III trial (N Engl J Med. 2017 Mar 2;376[9]:836-74), with 376 treated patients. In that trial, blinatumomab more than doubled the complete remission rate, compared with control patients (34% vs. 16%), and nearly doubled median overall survival – 7.7 months with blinatumomab, compared with 4.0 months for control patients treated with standard chemotherapy.
These findings “further substantiated” blinatumomab’s role, he said.
Blinatumomab’s big limitations are certain adverse effects and the logistics of its dosing. The major adverse effect is “cytokine release syndrome,” which manifests as fever, low blood pressure, and neurologic toxicities that can range from tremors to encephalopathy and seizure. These are manageable by close observation of patients by experienced nurses, Dr. DeAngelo said.
Dosing involves 4 weeks of continuous infusion, starting with 10 days done entirely in the hospital, with the remaining 18 days with patients going home but needing to return every 48 hours to have their infusion bag changed. “Depending on how far the patient lives from the clinic, it can be a logistical challenge,” he said.
A second new antibody he has used on many patients is inotuzumab, which was accepted for review for approval by the FDA in February 2017, with action expected by August.
Dr. DeAngelo served as a coinvestigator in a phase III trial reported in 2016 with 218 evaluable patients. In that trial, investigators reported an 81% complete remission rate with inotuzumab treatment, compared with a 29% among control patients on chemotherapy (N Engl J Med. 2016 Aug 25;375[8]:740-53).
Inotuzumab was effective against patients with Philadelphia chromosome positive ALL, but it will not work for the roughly 5%-10% of ALL patients who lack CD-22 expression in their B-cell ALL.
Inotuzumab is easier to administer than blinatumomab, requiring a once a week infusion, and causes little immediate toxicity – although thrombocytopenia and liver-function abnormalities can occur with continued use, and the risk of veno-occlusive disease is increased when patients later receive a stem cell transplant, Dr. DeAngelo said.
“It’s nice to have options” when choosing antibody-based treatment, he said. Blinatumomab is a good choice for patients with a lower tumor burden – either patients with early relapse or with minimal residual disease – while inotuzumab works better for patients with more bulky disease, as well as those who are not able to accommodate the logistic demands of blinatumomab infusions.
Dr. DeAngelo also highlighted several trials now underway that are testing the efficacy of both antibodies when used as part of first-line treatment.
Dr. DeAngelo has been a consultant to Amgen, the company that markets blinatumomab (Blincyto); to Pfizer, the company developing inotuzumab; and to Ariad, InCyte, and Novartis.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
mzoler@frontlinemedcom.com
On Twitter @mitchelzoler
NEW YORK – A pair of new monoclonal antibodies have dramatically changed treatment for patients with acute lymphoblastic leukemia to prepare them for a stem cell transplant, Daniel J. DeAngelo, MD, said at a conference held by Imedex.
“We don’t use standard chemotherapy for reinduction anymore; we use blinatumomab or inotuzumab,” said Dr. DeAngelo, a hematologist oncologist at Dana-Farber Cancer Institute in Boston.
Blinatumomab (Blincyto), approved by the Food and Drug Administration in 2014, has produced “exceptional” response rates, becoming “standard of care” for patients with relapsed acute lymphoblastic leukemia (ALL) that does not have a Philadelphia chromosome, Dr. DeAngelo said in a video interview.
Approved based on results from a phase II study, blinatumomab’s efficacy and safety were recently further delineated in results from the first phase III trial (N Engl J Med. 2017 Mar 2;376[9]:836-74), with 376 treated patients. In that trial, blinatumomab more than doubled the complete remission rate, compared with control patients (34% vs. 16%), and nearly doubled median overall survival – 7.7 months with blinatumomab, compared with 4.0 months for control patients treated with standard chemotherapy.
These findings “further substantiated” blinatumomab’s role, he said.
Blinatumomab’s big limitations are certain adverse effects and the logistics of its dosing. The major adverse effect is “cytokine release syndrome,” which manifests as fever, low blood pressure, and neurologic toxicities that can range from tremors to encephalopathy and seizure. These are manageable by close observation of patients by experienced nurses, Dr. DeAngelo said.
Dosing involves 4 weeks of continuous infusion, starting with 10 days done entirely in the hospital, with the remaining 18 days with patients going home but needing to return every 48 hours to have their infusion bag changed. “Depending on how far the patient lives from the clinic, it can be a logistical challenge,” he said.
A second new antibody he has used on many patients is inotuzumab, which was accepted for review for approval by the FDA in February 2017, with action expected by August.
Dr. DeAngelo served as a coinvestigator in a phase III trial reported in 2016 with 218 evaluable patients. In that trial, investigators reported an 81% complete remission rate with inotuzumab treatment, compared with a 29% among control patients on chemotherapy (N Engl J Med. 2016 Aug 25;375[8]:740-53).
Inotuzumab was effective against patients with Philadelphia chromosome positive ALL, but it will not work for the roughly 5%-10% of ALL patients who lack CD-22 expression in their B-cell ALL.
Inotuzumab is easier to administer than blinatumomab, requiring a once a week infusion, and causes little immediate toxicity – although thrombocytopenia and liver-function abnormalities can occur with continued use, and the risk of veno-occlusive disease is increased when patients later receive a stem cell transplant, Dr. DeAngelo said.
“It’s nice to have options” when choosing antibody-based treatment, he said. Blinatumomab is a good choice for patients with a lower tumor burden – either patients with early relapse or with minimal residual disease – while inotuzumab works better for patients with more bulky disease, as well as those who are not able to accommodate the logistic demands of blinatumomab infusions.
Dr. DeAngelo also highlighted several trials now underway that are testing the efficacy of both antibodies when used as part of first-line treatment.
Dr. DeAngelo has been a consultant to Amgen, the company that markets blinatumomab (Blincyto); to Pfizer, the company developing inotuzumab; and to Ariad, InCyte, and Novartis.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
mzoler@frontlinemedcom.com
On Twitter @mitchelzoler
NEW YORK – A pair of new monoclonal antibodies have dramatically changed treatment for patients with acute lymphoblastic leukemia to prepare them for a stem cell transplant, Daniel J. DeAngelo, MD, said at a conference held by Imedex.
“We don’t use standard chemotherapy for reinduction anymore; we use blinatumomab or inotuzumab,” said Dr. DeAngelo, a hematologist oncologist at Dana-Farber Cancer Institute in Boston.
Blinatumomab (Blincyto), approved by the Food and Drug Administration in 2014, has produced “exceptional” response rates, becoming “standard of care” for patients with relapsed acute lymphoblastic leukemia (ALL) that does not have a Philadelphia chromosome, Dr. DeAngelo said in a video interview.
Approved based on results from a phase II study, blinatumomab’s efficacy and safety were recently further delineated in results from the first phase III trial (N Engl J Med. 2017 Mar 2;376[9]:836-74), with 376 treated patients. In that trial, blinatumomab more than doubled the complete remission rate, compared with control patients (34% vs. 16%), and nearly doubled median overall survival – 7.7 months with blinatumomab, compared with 4.0 months for control patients treated with standard chemotherapy.
These findings “further substantiated” blinatumomab’s role, he said.
Blinatumomab’s big limitations are certain adverse effects and the logistics of its dosing. The major adverse effect is “cytokine release syndrome,” which manifests as fever, low blood pressure, and neurologic toxicities that can range from tremors to encephalopathy and seizure. These are manageable by close observation of patients by experienced nurses, Dr. DeAngelo said.
Dosing involves 4 weeks of continuous infusion, starting with 10 days done entirely in the hospital, with the remaining 18 days with patients going home but needing to return every 48 hours to have their infusion bag changed. “Depending on how far the patient lives from the clinic, it can be a logistical challenge,” he said.
A second new antibody he has used on many patients is inotuzumab, which was accepted for review for approval by the FDA in February 2017, with action expected by August.
Dr. DeAngelo served as a coinvestigator in a phase III trial reported in 2016 with 218 evaluable patients. In that trial, investigators reported an 81% complete remission rate with inotuzumab treatment, compared with a 29% among control patients on chemotherapy (N Engl J Med. 2016 Aug 25;375[8]:740-53).
Inotuzumab was effective against patients with Philadelphia chromosome positive ALL, but it will not work for the roughly 5%-10% of ALL patients who lack CD-22 expression in their B-cell ALL.
Inotuzumab is easier to administer than blinatumomab, requiring a once a week infusion, and causes little immediate toxicity – although thrombocytopenia and liver-function abnormalities can occur with continued use, and the risk of veno-occlusive disease is increased when patients later receive a stem cell transplant, Dr. DeAngelo said.
“It’s nice to have options” when choosing antibody-based treatment, he said. Blinatumomab is a good choice for patients with a lower tumor burden – either patients with early relapse or with minimal residual disease – while inotuzumab works better for patients with more bulky disease, as well as those who are not able to accommodate the logistic demands of blinatumomab infusions.
Dr. DeAngelo also highlighted several trials now underway that are testing the efficacy of both antibodies when used as part of first-line treatment.
Dr. DeAngelo has been a consultant to Amgen, the company that markets blinatumomab (Blincyto); to Pfizer, the company developing inotuzumab; and to Ariad, InCyte, and Novartis.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
mzoler@frontlinemedcom.com
On Twitter @mitchelzoler
EXPERT ANALYSIS FROM A MEETING ON HEMATOLOGIC MALIGNANCIES
Routine U.S. mitral clip use found reassuring
WASHINGTON – U.S. heart teams have used the mitral valve transcatheter clip repair device for fixing leaky mitral valves exactly the way it was designed to be used once the device hit the U.S. market in 2013.
In the first review of periprocedural and 1-year outcomes of U.S. patients treated with the MitraClip repair device and entered in the national device registry, the results showed “acute effectiveness and safety of transcatheter mitral valve repair,” Paul Sorajja, MD, said at the annual meeting of the American College of Cardiology.
“We need to be keenly aware of the impact of comorbidities on the prognosis of these patients. The data show that untreated comorbidities really impact prognosis,” said Dr. Sorajja, an interventional cardiologist and director of the Center of Valve and Structural Heart Disease of the Minneapolis Heart Institute.
“The clip is for the no-option patient, meaning patients at high risk who have no surgical option. The data show that these are the patients who are being treated” in routine U.S. practice. “The data show that, even for these patients, you can still get pretty good results,” Dr. Sorajja said in an interview. “These are the first data on clip use in routine U.S. practice, and they are really reassuring. The data show that the clip is being used in the correct way, without risk creep, on patients with prohibitive surgical risk based on their STS [Society of Thoracic Surgeons] predicted mortality and frailty scores.”
The data he and his associates reviewed came from the 2,952 U.S. patients who underwent a transcatheter mitral valve clip repair following the devices premarketing approval from the Food and Drug Administration in November 2013, and through September 2015 at any of 250 U.S. sites offering the procedure.
The data on patient demographics and clinical status came from the STS/American College of Cardiology Transcatheter Valve Therapy registry, and data on 1-year outcomes came from Medicare records for 1,867 (63%) of the patients.
The mitral valve repair patients averaged 82 years old, 85% had a New York Heart Association functional class of III or IV, 93% had a mitral valve regurgitation grade of 3 or 4, half were judged frail, and their STS predicted mortality risk from mitral valve repair was about 6% and from valve replacement about 9%.
Immediately after their procedure, 93% of patients had a valve regurgitation grade of 2 or less, the periprocedural mortality rate was just under 3%, and 86% of patients were discharged home following a median length of stay of 2 days. Acute procedural success occurred in 92% of patients, Dr. Sorajja reported.
At 1 year, the mortality rate among the patients followed through their Medicare records showed that 26% of patients had died, 20% had been hospitalized at least once for heart failure, and 38% had at least one of these two outcomes. In addition, 6% underwent a repeat procedure of transcatheter mitral repair, and 2% had mitral valve replacement surgery.
Although patients who had a successful repair with a residual regurgitation grade of 0 or 1 still had a substantial mortality rate of 22% during 1-year follow-up, survival was worse in patients with higher grades of residual mitral regurgitation. One-year mortality among those with residual grade 2 regurgitation was 29%, and for those with residual grade 3 or 4 regurgitation, 1-year mortality was 49%.
Many patients also had at least one comorbidity, and when these were present, 1-year survival was significantly worse. In a multivariate model, patients on dialysis had twofold greater mortality than did those not on dialysis, patients with severe tricuspid valve regurgitation had twice the mortality of those with lesser or no tricuspid regurgitation, and patients with moderate or severe lung disease had a 50% higher mortality, compared with those with milder or no lung disease.
The study was supported in part by Abbott Vascular, the company that markets the MitraClip. Dr. Sorajja has been a consultant to and speaker on behalf of Abbott Vascular. He has also been a consultant to Integer, Lake Region Medical, and Medtronic, and a speaker on behalf of Boston Scientific.
mzoler@frontlinemedcom.com
On Twitter @mitchelzoler
WASHINGTON – U.S. heart teams have used the mitral valve transcatheter clip repair device for fixing leaky mitral valves exactly the way it was designed to be used once the device hit the U.S. market in 2013.
In the first review of periprocedural and 1-year outcomes of U.S. patients treated with the MitraClip repair device and entered in the national device registry, the results showed “acute effectiveness and safety of transcatheter mitral valve repair,” Paul Sorajja, MD, said at the annual meeting of the American College of Cardiology.
“We need to be keenly aware of the impact of comorbidities on the prognosis of these patients. The data show that untreated comorbidities really impact prognosis,” said Dr. Sorajja, an interventional cardiologist and director of the Center of Valve and Structural Heart Disease of the Minneapolis Heart Institute.
“The clip is for the no-option patient, meaning patients at high risk who have no surgical option. The data show that these are the patients who are being treated” in routine U.S. practice. “The data show that, even for these patients, you can still get pretty good results,” Dr. Sorajja said in an interview. “These are the first data on clip use in routine U.S. practice, and they are really reassuring. The data show that the clip is being used in the correct way, without risk creep, on patients with prohibitive surgical risk based on their STS [Society of Thoracic Surgeons] predicted mortality and frailty scores.”
The data he and his associates reviewed came from the 2,952 U.S. patients who underwent a transcatheter mitral valve clip repair following the devices premarketing approval from the Food and Drug Administration in November 2013, and through September 2015 at any of 250 U.S. sites offering the procedure.
The data on patient demographics and clinical status came from the STS/American College of Cardiology Transcatheter Valve Therapy registry, and data on 1-year outcomes came from Medicare records for 1,867 (63%) of the patients.
The mitral valve repair patients averaged 82 years old, 85% had a New York Heart Association functional class of III or IV, 93% had a mitral valve regurgitation grade of 3 or 4, half were judged frail, and their STS predicted mortality risk from mitral valve repair was about 6% and from valve replacement about 9%.
Immediately after their procedure, 93% of patients had a valve regurgitation grade of 2 or less, the periprocedural mortality rate was just under 3%, and 86% of patients were discharged home following a median length of stay of 2 days. Acute procedural success occurred in 92% of patients, Dr. Sorajja reported.
At 1 year, the mortality rate among the patients followed through their Medicare records showed that 26% of patients had died, 20% had been hospitalized at least once for heart failure, and 38% had at least one of these two outcomes. In addition, 6% underwent a repeat procedure of transcatheter mitral repair, and 2% had mitral valve replacement surgery.
Although patients who had a successful repair with a residual regurgitation grade of 0 or 1 still had a substantial mortality rate of 22% during 1-year follow-up, survival was worse in patients with higher grades of residual mitral regurgitation. One-year mortality among those with residual grade 2 regurgitation was 29%, and for those with residual grade 3 or 4 regurgitation, 1-year mortality was 49%.
Many patients also had at least one comorbidity, and when these were present, 1-year survival was significantly worse. In a multivariate model, patients on dialysis had twofold greater mortality than did those not on dialysis, patients with severe tricuspid valve regurgitation had twice the mortality of those with lesser or no tricuspid regurgitation, and patients with moderate or severe lung disease had a 50% higher mortality, compared with those with milder or no lung disease.
The study was supported in part by Abbott Vascular, the company that markets the MitraClip. Dr. Sorajja has been a consultant to and speaker on behalf of Abbott Vascular. He has also been a consultant to Integer, Lake Region Medical, and Medtronic, and a speaker on behalf of Boston Scientific.
mzoler@frontlinemedcom.com
On Twitter @mitchelzoler
WASHINGTON – U.S. heart teams have used the mitral valve transcatheter clip repair device for fixing leaky mitral valves exactly the way it was designed to be used once the device hit the U.S. market in 2013.
In the first review of periprocedural and 1-year outcomes of U.S. patients treated with the MitraClip repair device and entered in the national device registry, the results showed “acute effectiveness and safety of transcatheter mitral valve repair,” Paul Sorajja, MD, said at the annual meeting of the American College of Cardiology.
“We need to be keenly aware of the impact of comorbidities on the prognosis of these patients. The data show that untreated comorbidities really impact prognosis,” said Dr. Sorajja, an interventional cardiologist and director of the Center of Valve and Structural Heart Disease of the Minneapolis Heart Institute.
“The clip is for the no-option patient, meaning patients at high risk who have no surgical option. The data show that these are the patients who are being treated” in routine U.S. practice. “The data show that, even for these patients, you can still get pretty good results,” Dr. Sorajja said in an interview. “These are the first data on clip use in routine U.S. practice, and they are really reassuring. The data show that the clip is being used in the correct way, without risk creep, on patients with prohibitive surgical risk based on their STS [Society of Thoracic Surgeons] predicted mortality and frailty scores.”
The data he and his associates reviewed came from the 2,952 U.S. patients who underwent a transcatheter mitral valve clip repair following the devices premarketing approval from the Food and Drug Administration in November 2013, and through September 2015 at any of 250 U.S. sites offering the procedure.
The data on patient demographics and clinical status came from the STS/American College of Cardiology Transcatheter Valve Therapy registry, and data on 1-year outcomes came from Medicare records for 1,867 (63%) of the patients.
The mitral valve repair patients averaged 82 years old, 85% had a New York Heart Association functional class of III or IV, 93% had a mitral valve regurgitation grade of 3 or 4, half were judged frail, and their STS predicted mortality risk from mitral valve repair was about 6% and from valve replacement about 9%.
Immediately after their procedure, 93% of patients had a valve regurgitation grade of 2 or less, the periprocedural mortality rate was just under 3%, and 86% of patients were discharged home following a median length of stay of 2 days. Acute procedural success occurred in 92% of patients, Dr. Sorajja reported.
At 1 year, the mortality rate among the patients followed through their Medicare records showed that 26% of patients had died, 20% had been hospitalized at least once for heart failure, and 38% had at least one of these two outcomes. In addition, 6% underwent a repeat procedure of transcatheter mitral repair, and 2% had mitral valve replacement surgery.
Although patients who had a successful repair with a residual regurgitation grade of 0 or 1 still had a substantial mortality rate of 22% during 1-year follow-up, survival was worse in patients with higher grades of residual mitral regurgitation. One-year mortality among those with residual grade 2 regurgitation was 29%, and for those with residual grade 3 or 4 regurgitation, 1-year mortality was 49%.
Many patients also had at least one comorbidity, and when these were present, 1-year survival was significantly worse. In a multivariate model, patients on dialysis had twofold greater mortality than did those not on dialysis, patients with severe tricuspid valve regurgitation had twice the mortality of those with lesser or no tricuspid regurgitation, and patients with moderate or severe lung disease had a 50% higher mortality, compared with those with milder or no lung disease.
The study was supported in part by Abbott Vascular, the company that markets the MitraClip. Dr. Sorajja has been a consultant to and speaker on behalf of Abbott Vascular. He has also been a consultant to Integer, Lake Region Medical, and Medtronic, and a speaker on behalf of Boston Scientific.
mzoler@frontlinemedcom.com
On Twitter @mitchelzoler
AT ACC 17
Key clinical point:
Major finding: U.S. mitral clip patients averaged 82 years of age, their acute success rate was 92%, and 1-year mortality was 26%.
Data source: A review of 2,952 U.S. patients who underwent transcatheter mitral clip repair and entered into the STS/ACC/TVT registry through September 2015.
Disclosures: The study was supported in part by Abbott Vascular, the company that markets the MitraClip. Dr. Sorajja has been a consultant to and speaker on behalf of Abbott Vascular. He has also been a consultant to Integer, Lake Region Medical, and Medtronic, and a speaker on behalf of Boston Scientific.
VIDEO: Careful TKI hiatus makes CML pregnancy possible
NEW YORK – The success that tyrosine kinase inhibitors have had in prolonging life and producing deep hematologic and molecular remissions in patients with chronic myeloid leukemia has led to an unexpected bonus for young women living with the disease: an opportunity to safely become pregnant and mother a child.
The approach is not yet routine and poses a level of risk to both the mother and fetus, especially because tyrosine kinase inhibitors (TKIs) are teratogenic. But with careful planning, close gestational monitoring, and with support from skilled obstetricians, the scenario of a successful pregnancy in women with chronic myeloid leukemia (CML) has now played out several dozen times at a handful of U.S. centers, Mrinal S. Patnaik, MD, said in a talk at the conference held by Imedex.
“We make it clear that this is experimental and is associated with risk, and we share the data [from case reports]; but if the woman wants to go forward,” a protocol now exists “to successfully get them to pregnancy,” said Dr. Patnaik, a hematologist oncologist at the Mayo Clinic in Rochester, Minn.
At Mayo alone, upwards of 20 women with CML have been successfully shepherded through pregnancy, he said in a video interview.
The prospect for a planned pregnancy is reserved for women with their CML well controlled for at least 2 years using a TKI, most often imatinib (Gleevec). In addition to being under complete hematologic control, the candidate patient must also show a deep molecular response, which means a blood level of the BRC-ABL tyrosine kinase that drives CML at least 4 or 4.5 logs (10,000-50,000-fold) below pretreatment levels or molecularly undetectable.
The patient then monitors her ovulatory cycle and stops her medication at the time of ovulation, attempts conception, and then monitors whether pregnancy has actually started. If it has, she needs to stay off her TKI regimen through at least the first 18 weeks of gestation, although an even longer drug holiday is preferred. If not, she resumes the medication and repeats the process later if she wants.
Once the women is pregnant and remains off her TKI regimen Dr. Patnaik and his associates closely follow the woman for signs of a molecular or hematologic relapse, although the latter are unusual. If a resurgence of CML stem cells occurs, the woman receives treatment with pegylated interferon-alpha, which is safe during pregnancy. When possible, TKI treatment remains on hold into the breast-feeding period.
During pregnancy and delivery, the patient requires careful and regular follow-up by a maternal-fetal medicine specialist and has an ongoing risk for high platelet counts causing placental blood clots, fetuses that are small for gestational age, preterm labor, premature rupture of membranes, and other complications.
“These are manageable with good obstetrical care,” Dr. Patnaik said. “We have developed a good system to work out the obstetrical complications.
“By and large we can be successful, but it requires a lot of monitoring and a lot of patient compliance with regular follow-ups,” he stressed.
In a video interview at the meeting, Dr. Patnaik discussed the approach he takes with his patients.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
mzoler@frontlinemedcom.com
On Twitter @mitchelzoler
NEW YORK – The success that tyrosine kinase inhibitors have had in prolonging life and producing deep hematologic and molecular remissions in patients with chronic myeloid leukemia has led to an unexpected bonus for young women living with the disease: an opportunity to safely become pregnant and mother a child.
The approach is not yet routine and poses a level of risk to both the mother and fetus, especially because tyrosine kinase inhibitors (TKIs) are teratogenic. But with careful planning, close gestational monitoring, and with support from skilled obstetricians, the scenario of a successful pregnancy in women with chronic myeloid leukemia (CML) has now played out several dozen times at a handful of U.S. centers, Mrinal S. Patnaik, MD, said in a talk at the conference held by Imedex.
“We make it clear that this is experimental and is associated with risk, and we share the data [from case reports]; but if the woman wants to go forward,” a protocol now exists “to successfully get them to pregnancy,” said Dr. Patnaik, a hematologist oncologist at the Mayo Clinic in Rochester, Minn.
At Mayo alone, upwards of 20 women with CML have been successfully shepherded through pregnancy, he said in a video interview.
The prospect for a planned pregnancy is reserved for women with their CML well controlled for at least 2 years using a TKI, most often imatinib (Gleevec). In addition to being under complete hematologic control, the candidate patient must also show a deep molecular response, which means a blood level of the BRC-ABL tyrosine kinase that drives CML at least 4 or 4.5 logs (10,000-50,000-fold) below pretreatment levels or molecularly undetectable.
The patient then monitors her ovulatory cycle and stops her medication at the time of ovulation, attempts conception, and then monitors whether pregnancy has actually started. If it has, she needs to stay off her TKI regimen through at least the first 18 weeks of gestation, although an even longer drug holiday is preferred. If not, she resumes the medication and repeats the process later if she wants.
Once the women is pregnant and remains off her TKI regimen Dr. Patnaik and his associates closely follow the woman for signs of a molecular or hematologic relapse, although the latter are unusual. If a resurgence of CML stem cells occurs, the woman receives treatment with pegylated interferon-alpha, which is safe during pregnancy. When possible, TKI treatment remains on hold into the breast-feeding period.
During pregnancy and delivery, the patient requires careful and regular follow-up by a maternal-fetal medicine specialist and has an ongoing risk for high platelet counts causing placental blood clots, fetuses that are small for gestational age, preterm labor, premature rupture of membranes, and other complications.
“These are manageable with good obstetrical care,” Dr. Patnaik said. “We have developed a good system to work out the obstetrical complications.
“By and large we can be successful, but it requires a lot of monitoring and a lot of patient compliance with regular follow-ups,” he stressed.
In a video interview at the meeting, Dr. Patnaik discussed the approach he takes with his patients.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
mzoler@frontlinemedcom.com
On Twitter @mitchelzoler
NEW YORK – The success that tyrosine kinase inhibitors have had in prolonging life and producing deep hematologic and molecular remissions in patients with chronic myeloid leukemia has led to an unexpected bonus for young women living with the disease: an opportunity to safely become pregnant and mother a child.
The approach is not yet routine and poses a level of risk to both the mother and fetus, especially because tyrosine kinase inhibitors (TKIs) are teratogenic. But with careful planning, close gestational monitoring, and with support from skilled obstetricians, the scenario of a successful pregnancy in women with chronic myeloid leukemia (CML) has now played out several dozen times at a handful of U.S. centers, Mrinal S. Patnaik, MD, said in a talk at the conference held by Imedex.
“We make it clear that this is experimental and is associated with risk, and we share the data [from case reports]; but if the woman wants to go forward,” a protocol now exists “to successfully get them to pregnancy,” said Dr. Patnaik, a hematologist oncologist at the Mayo Clinic in Rochester, Minn.
At Mayo alone, upwards of 20 women with CML have been successfully shepherded through pregnancy, he said in a video interview.
The prospect for a planned pregnancy is reserved for women with their CML well controlled for at least 2 years using a TKI, most often imatinib (Gleevec). In addition to being under complete hematologic control, the candidate patient must also show a deep molecular response, which means a blood level of the BRC-ABL tyrosine kinase that drives CML at least 4 or 4.5 logs (10,000-50,000-fold) below pretreatment levels or molecularly undetectable.
The patient then monitors her ovulatory cycle and stops her medication at the time of ovulation, attempts conception, and then monitors whether pregnancy has actually started. If it has, she needs to stay off her TKI regimen through at least the first 18 weeks of gestation, although an even longer drug holiday is preferred. If not, she resumes the medication and repeats the process later if she wants.
Once the women is pregnant and remains off her TKI regimen Dr. Patnaik and his associates closely follow the woman for signs of a molecular or hematologic relapse, although the latter are unusual. If a resurgence of CML stem cells occurs, the woman receives treatment with pegylated interferon-alpha, which is safe during pregnancy. When possible, TKI treatment remains on hold into the breast-feeding period.
During pregnancy and delivery, the patient requires careful and regular follow-up by a maternal-fetal medicine specialist and has an ongoing risk for high platelet counts causing placental blood clots, fetuses that are small for gestational age, preterm labor, premature rupture of membranes, and other complications.
“These are manageable with good obstetrical care,” Dr. Patnaik said. “We have developed a good system to work out the obstetrical complications.
“By and large we can be successful, but it requires a lot of monitoring and a lot of patient compliance with regular follow-ups,” he stressed.
In a video interview at the meeting, Dr. Patnaik discussed the approach he takes with his patients.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
mzoler@frontlinemedcom.com
On Twitter @mitchelzoler
EXPERT ANALYSIS FROM A MEETING ON HEMATOLOGIC MALIGNANCIES
Decision tool helps patients compare SAVR, TAVR
WASHINGTON – A decision-assistance tool will soon be available that is designed to help intermediate-risk patients with severe aortic stenosis and their physicians better compare each patient’s expected outcome from surgical or transcatheter valve replacement based on each patient’s individual clinical and demographic features.
The decision tool will be available as both a web-based calculator and a downloadable app. It is derived from the outcomes of 4,732 patients who underwent surgical aortic valve replacement (SAVR) during 2011-2013 and who were included in the registry maintained by the Society of Thoracic Surgeons (STS), as well as an equal number of closely matched patients who underwent transcatheter aortic valve replacement (TAVR) during 2014-2015 and entered in the Transcatheter Valve (TVT) registry run by STS and the American College of Cardiology. Tool development also used longer-term outcomes data collected through Medicare.
After receiving patient-specific data, the decision tool estimates the patient’s short-term and 1-year predicted risks for death and stroke and likelihood of being discharged home, as well as the predicted number of days the patient would remain alive and out of the hospital during the first postprocedural year, J. Matthew Brennan, MD, said at the annual meeting of the American College of Cardiology.
Cardiologists and cardiac surgeons “are desperately looking for something like this” because, currently, the only option is to estimate a patient’s risk after SAVR or TAVR using tools developed only from patients who underwent one of these procedures. The new tool gives clinicians and patients a way to compare the two options for an individual patient in a way that “minimizes the biases,” said Dr. Brennan, an interventional cardiologist at Duke University in Durham, N.C., and principal investigator for development of the website and the tool.
Dr. Brennan and his associates developed the decision assistance tool with funding from the Patient-Center Outcomes Research Institute, and it will be available online at no cost at valveadvice.org. The website was already up and running when Dr. Brennan announced the tool during the meeting, and it currently has patient-centered information about aortic valve disease and the options available for treating it. He expects the decision tool to be posted on the site by April or May.
The data he and his associates used to create the decision tool came from a total of more than 197,000 SAVR patients entered into the STS SAVR database during 2011-2013 and more than 25,000 TAVR patients enrolled in the TVT registry during 2014-2015. They used propensity score matching to identify 4,732 matched patients from each group. The patients averaged 81-82 years old, nearly half were women, and their average STS risk score was 5.5-5.8, which meant that patients fell in an intermediate-risk range by this criterion. Just over three-quarters of the TAVR patients had their procedure done via a transfemoral route.
The analysis showed that, overall, 1-year mortality and stroke rates following each type of procedure were not significantly different, and several subgroup analyses failed to identify any type of patient who fell outside this overall pattern. The TAVR patients had a stroke rate that continued to rise during 12-month follow-up, compared with a much flatter pattern among the SAVR patients. While this did not result in an excess stroke rate, the pattern over time suggested that TAVR patients may not have received optimal anticoagulant treatment during the year following their procedure, Dr. Brennan said. The number of months that patients were alive and not hospitalized was also very similar in the SAVR and TAVR groups.
While the 1-year outcomes were very similar, the periprocedural outcomes showed several statistically significant differences. In-hospital mortality was significantly higher in the SAVR patients at 5%, compared with 3% in the TAVR patients. The SAVR patients also were significantly more likely to develop a need for dialysis and a need for red cells and to have a doubled duration in their ICU stay and in their postprocedural length of hospitalization, compared with TAVR patients. On the other hand, TAVR patients were significantly more likely to need a new pacemaker while hospitalized and had a 10 times higher rate of major vascular complications. The stroke rates were very similar in both arms, Dr. Brennan reported.
According to Dr. Brennan, the most striking difference in hospital outcomes was the discharge destination for patients: 70% of TAVR patients went home after their procedural hospitalization, compared with 41% of the SAVR patients. Discharges home following periprocedural hospitalization were “substantially higher” with TAVR, he said.
Another notable feature of these data was how they contrasted with the 1-year outcomes reported from the German Aortic Valve Registry at the American Heart Association Scientific Sessions in November 2016. In the German registry, 1-year mortality after propensity-score adjustment was about 11% among SAVR patients and about 14% among TAVR patients treated with a transfemoral approach, a statistically significant difference, reported Nicolas Werner, MD, of the Ludwigshafen (Germany) Clinic.
“I think the reason we see a difference in the German data is they weren’t able to remove from their analysis the really high-risk patients” who preferentially underwent TAVR, suggested Dr. Brennan. “We had the ability to match patients who had equipoise for undergoing SAVR or TAVR. That’s why our results are more consistent with the findings from the TAVR clinical trials.”
“One of the most important findings from [Dr. Brennan’s] study is [that] it makes the German Registry results look like the outliers rather than the results from the TAVR clinical trials,” commented Howard C. Hermann, MD, professor of cardiovascular disease and director of the cardiac catheterization laboratories at the University of Pennsylvania in Philadelphia.
The data analysis and development of the valveadvice.org website and decision tool received no commercial support. Dr. Brennan had no disclosures. Dr. Hermann has received honoraria and research support from Edwards Pharmaceuticals, research support from Medtronic, and honoraria and research support from several other companies.
mzoler@frontlinemedcom.com
On Twitter @mitchelzoler
WASHINGTON – A decision-assistance tool will soon be available that is designed to help intermediate-risk patients with severe aortic stenosis and their physicians better compare each patient’s expected outcome from surgical or transcatheter valve replacement based on each patient’s individual clinical and demographic features.
The decision tool will be available as both a web-based calculator and a downloadable app. It is derived from the outcomes of 4,732 patients who underwent surgical aortic valve replacement (SAVR) during 2011-2013 and who were included in the registry maintained by the Society of Thoracic Surgeons (STS), as well as an equal number of closely matched patients who underwent transcatheter aortic valve replacement (TAVR) during 2014-2015 and entered in the Transcatheter Valve (TVT) registry run by STS and the American College of Cardiology. Tool development also used longer-term outcomes data collected through Medicare.
After receiving patient-specific data, the decision tool estimates the patient’s short-term and 1-year predicted risks for death and stroke and likelihood of being discharged home, as well as the predicted number of days the patient would remain alive and out of the hospital during the first postprocedural year, J. Matthew Brennan, MD, said at the annual meeting of the American College of Cardiology.
Cardiologists and cardiac surgeons “are desperately looking for something like this” because, currently, the only option is to estimate a patient’s risk after SAVR or TAVR using tools developed only from patients who underwent one of these procedures. The new tool gives clinicians and patients a way to compare the two options for an individual patient in a way that “minimizes the biases,” said Dr. Brennan, an interventional cardiologist at Duke University in Durham, N.C., and principal investigator for development of the website and the tool.
Dr. Brennan and his associates developed the decision assistance tool with funding from the Patient-Center Outcomes Research Institute, and it will be available online at no cost at valveadvice.org. The website was already up and running when Dr. Brennan announced the tool during the meeting, and it currently has patient-centered information about aortic valve disease and the options available for treating it. He expects the decision tool to be posted on the site by April or May.
The data he and his associates used to create the decision tool came from a total of more than 197,000 SAVR patients entered into the STS SAVR database during 2011-2013 and more than 25,000 TAVR patients enrolled in the TVT registry during 2014-2015. They used propensity score matching to identify 4,732 matched patients from each group. The patients averaged 81-82 years old, nearly half were women, and their average STS risk score was 5.5-5.8, which meant that patients fell in an intermediate-risk range by this criterion. Just over three-quarters of the TAVR patients had their procedure done via a transfemoral route.
The analysis showed that, overall, 1-year mortality and stroke rates following each type of procedure were not significantly different, and several subgroup analyses failed to identify any type of patient who fell outside this overall pattern. The TAVR patients had a stroke rate that continued to rise during 12-month follow-up, compared with a much flatter pattern among the SAVR patients. While this did not result in an excess stroke rate, the pattern over time suggested that TAVR patients may not have received optimal anticoagulant treatment during the year following their procedure, Dr. Brennan said. The number of months that patients were alive and not hospitalized was also very similar in the SAVR and TAVR groups.
While the 1-year outcomes were very similar, the periprocedural outcomes showed several statistically significant differences. In-hospital mortality was significantly higher in the SAVR patients at 5%, compared with 3% in the TAVR patients. The SAVR patients also were significantly more likely to develop a need for dialysis and a need for red cells and to have a doubled duration in their ICU stay and in their postprocedural length of hospitalization, compared with TAVR patients. On the other hand, TAVR patients were significantly more likely to need a new pacemaker while hospitalized and had a 10 times higher rate of major vascular complications. The stroke rates were very similar in both arms, Dr. Brennan reported.
According to Dr. Brennan, the most striking difference in hospital outcomes was the discharge destination for patients: 70% of TAVR patients went home after their procedural hospitalization, compared with 41% of the SAVR patients. Discharges home following periprocedural hospitalization were “substantially higher” with TAVR, he said.
Another notable feature of these data was how they contrasted with the 1-year outcomes reported from the German Aortic Valve Registry at the American Heart Association Scientific Sessions in November 2016. In the German registry, 1-year mortality after propensity-score adjustment was about 11% among SAVR patients and about 14% among TAVR patients treated with a transfemoral approach, a statistically significant difference, reported Nicolas Werner, MD, of the Ludwigshafen (Germany) Clinic.
“I think the reason we see a difference in the German data is they weren’t able to remove from their analysis the really high-risk patients” who preferentially underwent TAVR, suggested Dr. Brennan. “We had the ability to match patients who had equipoise for undergoing SAVR or TAVR. That’s why our results are more consistent with the findings from the TAVR clinical trials.”
“One of the most important findings from [Dr. Brennan’s] study is [that] it makes the German Registry results look like the outliers rather than the results from the TAVR clinical trials,” commented Howard C. Hermann, MD, professor of cardiovascular disease and director of the cardiac catheterization laboratories at the University of Pennsylvania in Philadelphia.
The data analysis and development of the valveadvice.org website and decision tool received no commercial support. Dr. Brennan had no disclosures. Dr. Hermann has received honoraria and research support from Edwards Pharmaceuticals, research support from Medtronic, and honoraria and research support from several other companies.
mzoler@frontlinemedcom.com
On Twitter @mitchelzoler
WASHINGTON – A decision-assistance tool will soon be available that is designed to help intermediate-risk patients with severe aortic stenosis and their physicians better compare each patient’s expected outcome from surgical or transcatheter valve replacement based on each patient’s individual clinical and demographic features.
The decision tool will be available as both a web-based calculator and a downloadable app. It is derived from the outcomes of 4,732 patients who underwent surgical aortic valve replacement (SAVR) during 2011-2013 and who were included in the registry maintained by the Society of Thoracic Surgeons (STS), as well as an equal number of closely matched patients who underwent transcatheter aortic valve replacement (TAVR) during 2014-2015 and entered in the Transcatheter Valve (TVT) registry run by STS and the American College of Cardiology. Tool development also used longer-term outcomes data collected through Medicare.
After receiving patient-specific data, the decision tool estimates the patient’s short-term and 1-year predicted risks for death and stroke and likelihood of being discharged home, as well as the predicted number of days the patient would remain alive and out of the hospital during the first postprocedural year, J. Matthew Brennan, MD, said at the annual meeting of the American College of Cardiology.
Cardiologists and cardiac surgeons “are desperately looking for something like this” because, currently, the only option is to estimate a patient’s risk after SAVR or TAVR using tools developed only from patients who underwent one of these procedures. The new tool gives clinicians and patients a way to compare the two options for an individual patient in a way that “minimizes the biases,” said Dr. Brennan, an interventional cardiologist at Duke University in Durham, N.C., and principal investigator for development of the website and the tool.
Dr. Brennan and his associates developed the decision assistance tool with funding from the Patient-Center Outcomes Research Institute, and it will be available online at no cost at valveadvice.org. The website was already up and running when Dr. Brennan announced the tool during the meeting, and it currently has patient-centered information about aortic valve disease and the options available for treating it. He expects the decision tool to be posted on the site by April or May.
The data he and his associates used to create the decision tool came from a total of more than 197,000 SAVR patients entered into the STS SAVR database during 2011-2013 and more than 25,000 TAVR patients enrolled in the TVT registry during 2014-2015. They used propensity score matching to identify 4,732 matched patients from each group. The patients averaged 81-82 years old, nearly half were women, and their average STS risk score was 5.5-5.8, which meant that patients fell in an intermediate-risk range by this criterion. Just over three-quarters of the TAVR patients had their procedure done via a transfemoral route.
The analysis showed that, overall, 1-year mortality and stroke rates following each type of procedure were not significantly different, and several subgroup analyses failed to identify any type of patient who fell outside this overall pattern. The TAVR patients had a stroke rate that continued to rise during 12-month follow-up, compared with a much flatter pattern among the SAVR patients. While this did not result in an excess stroke rate, the pattern over time suggested that TAVR patients may not have received optimal anticoagulant treatment during the year following their procedure, Dr. Brennan said. The number of months that patients were alive and not hospitalized was also very similar in the SAVR and TAVR groups.
While the 1-year outcomes were very similar, the periprocedural outcomes showed several statistically significant differences. In-hospital mortality was significantly higher in the SAVR patients at 5%, compared with 3% in the TAVR patients. The SAVR patients also were significantly more likely to develop a need for dialysis and a need for red cells and to have a doubled duration in their ICU stay and in their postprocedural length of hospitalization, compared with TAVR patients. On the other hand, TAVR patients were significantly more likely to need a new pacemaker while hospitalized and had a 10 times higher rate of major vascular complications. The stroke rates were very similar in both arms, Dr. Brennan reported.
According to Dr. Brennan, the most striking difference in hospital outcomes was the discharge destination for patients: 70% of TAVR patients went home after their procedural hospitalization, compared with 41% of the SAVR patients. Discharges home following periprocedural hospitalization were “substantially higher” with TAVR, he said.
Another notable feature of these data was how they contrasted with the 1-year outcomes reported from the German Aortic Valve Registry at the American Heart Association Scientific Sessions in November 2016. In the German registry, 1-year mortality after propensity-score adjustment was about 11% among SAVR patients and about 14% among TAVR patients treated with a transfemoral approach, a statistically significant difference, reported Nicolas Werner, MD, of the Ludwigshafen (Germany) Clinic.
“I think the reason we see a difference in the German data is they weren’t able to remove from their analysis the really high-risk patients” who preferentially underwent TAVR, suggested Dr. Brennan. “We had the ability to match patients who had equipoise for undergoing SAVR or TAVR. That’s why our results are more consistent with the findings from the TAVR clinical trials.”
“One of the most important findings from [Dr. Brennan’s] study is [that] it makes the German Registry results look like the outliers rather than the results from the TAVR clinical trials,” commented Howard C. Hermann, MD, professor of cardiovascular disease and director of the cardiac catheterization laboratories at the University of Pennsylvania in Philadelphia.
The data analysis and development of the valveadvice.org website and decision tool received no commercial support. Dr. Brennan had no disclosures. Dr. Hermann has received honoraria and research support from Edwards Pharmaceuticals, research support from Medtronic, and honoraria and research support from several other companies.
mzoler@frontlinemedcom.com
On Twitter @mitchelzoler
AT ACC 17
Key clinical point:
Major finding: In matched U.S. patients, TAVR led to 29% more patients being discharged home following their procedures, compared with SAVR.
Data source: Records for 9,464 U.S. patients who underwent TAVR or SAVR during 2011-2015.
Disclosures: Data analysis and development of the valveadvice.org website and decision tool received no commercial support. Dr. Brennan had no disclosures. Dr. Hermann has received honoraria and research support from Edwards Pharmaceuticals, research support from Medtronic, and honoraria and research support from several other companies.
Stroke hospitals owe all patients rapid thrombolysis
The best way to minimize death and disability in most patients having an acute ischemic stroke is rapid thrombolysis by infusion of tissue plasminogen activator. Mechanical clot removal – thrombectomy – has recently been shown even better, but it’s applicable to just a fraction of these stroke patients, and even for them thrombolysis remains, for the time being, the recommended first step, with thrombectomy following soon after.
The good news is that more eligible U.S. stroke patients than ever before get this effective treatment. As I reported recently from the International Stroke Conference, as of mid-2016, 68% of U.S. acute ischemic stroke patients treated at about 2,000 of the largest and most focused U.S. stroke hospitals received thrombolytic treatment within 60 minutes of their hospital arrival. That’s up from 30% in late 2009. Hooray! The sad news is that many eligible stroke patients seen at these hospitals don’t get treated this way. Simple math puts that figure at 32%. In other words, last year, nearly a third of U.S. stroke patients who should have received quick thrombolysis didn’t, even though they were taken to the country’s top stroke hospitals.
How do I know that more universal rapid thrombolysis is possible? The 2016 numbers reported from the Get With the Guidelines (GWTG)–Stroke hospitals showed that roughly 2% of the 788 hospitals included in this analysis treated 90% or more of their eligible stroke patients with thrombolysis within an hour. That’s about 16 hospitals. Another 8%, upward of 60 hospitals, treated 80%-89% of their eligible stroke patients within this window. So a high level of thrombolysis treatment is possible. It just isn’t being done everywhere. About 20% of the hospitals in the program treated 40% or fewer of eligible patients they saw within the 60-minute window.
I have no idea why some hospitals do so well while others don’t, despite being in the GWTG-Stroke program that promotes excellence in stroke care delivery. In the most recent iteration of the GWTG–Stroke Target Stroke program, phase II, the organization promoted 11 steps for hospitals to take to optimize rapid delivery of thrombolysis. The obvious inference is that some hospitals are doing all 11 steps very well and consistently, and many others aren’t. Underperforming hospitals owe it to their patients to do a much better job; the top-performing hospitals show it’s possible.
I have heard a lot recently at meetings about how research has established that a range of medical treatments, if used diligently by patients as directed, will substantially improve and prolong their life. Patient compliance then becomes a big issue, and so now I’m hearing more about new approaches to improve compliance. But what about hospital compliance?
Treating acute ischemic stroke as well as possible is different from most disorders – it’s not about patient compliance. It’s about the ambulance that picks up the patient and the hospital where the patient gets taken. The success or failure of the acute treatment that the roughly 700,000 annual U.S. acute ischemic stroke patients receive lies entirely in the hands of the hospital staff. Fewer than 10% of U.S. stroke hospitals offer the vast majority of these patients the best care currently available. Many others don’t do as well, and a huge fraction remain woefully slow, even though everyone knows the pathway to doing better. Underperforming hospitals owe it to patients to up their game, and they need to start doing it now.
mzoler@frontlinemedcom.com
On Twitter @mitchelzoler
The best way to minimize death and disability in most patients having an acute ischemic stroke is rapid thrombolysis by infusion of tissue plasminogen activator. Mechanical clot removal – thrombectomy – has recently been shown even better, but it’s applicable to just a fraction of these stroke patients, and even for them thrombolysis remains, for the time being, the recommended first step, with thrombectomy following soon after.
The good news is that more eligible U.S. stroke patients than ever before get this effective treatment. As I reported recently from the International Stroke Conference, as of mid-2016, 68% of U.S. acute ischemic stroke patients treated at about 2,000 of the largest and most focused U.S. stroke hospitals received thrombolytic treatment within 60 minutes of their hospital arrival. That’s up from 30% in late 2009. Hooray! The sad news is that many eligible stroke patients seen at these hospitals don’t get treated this way. Simple math puts that figure at 32%. In other words, last year, nearly a third of U.S. stroke patients who should have received quick thrombolysis didn’t, even though they were taken to the country’s top stroke hospitals.
How do I know that more universal rapid thrombolysis is possible? The 2016 numbers reported from the Get With the Guidelines (GWTG)–Stroke hospitals showed that roughly 2% of the 788 hospitals included in this analysis treated 90% or more of their eligible stroke patients with thrombolysis within an hour. That’s about 16 hospitals. Another 8%, upward of 60 hospitals, treated 80%-89% of their eligible stroke patients within this window. So a high level of thrombolysis treatment is possible. It just isn’t being done everywhere. About 20% of the hospitals in the program treated 40% or fewer of eligible patients they saw within the 60-minute window.
I have no idea why some hospitals do so well while others don’t, despite being in the GWTG-Stroke program that promotes excellence in stroke care delivery. In the most recent iteration of the GWTG–Stroke Target Stroke program, phase II, the organization promoted 11 steps for hospitals to take to optimize rapid delivery of thrombolysis. The obvious inference is that some hospitals are doing all 11 steps very well and consistently, and many others aren’t. Underperforming hospitals owe it to their patients to do a much better job; the top-performing hospitals show it’s possible.
I have heard a lot recently at meetings about how research has established that a range of medical treatments, if used diligently by patients as directed, will substantially improve and prolong their life. Patient compliance then becomes a big issue, and so now I’m hearing more about new approaches to improve compliance. But what about hospital compliance?
Treating acute ischemic stroke as well as possible is different from most disorders – it’s not about patient compliance. It’s about the ambulance that picks up the patient and the hospital where the patient gets taken. The success or failure of the acute treatment that the roughly 700,000 annual U.S. acute ischemic stroke patients receive lies entirely in the hands of the hospital staff. Fewer than 10% of U.S. stroke hospitals offer the vast majority of these patients the best care currently available. Many others don’t do as well, and a huge fraction remain woefully slow, even though everyone knows the pathway to doing better. Underperforming hospitals owe it to patients to up their game, and they need to start doing it now.
mzoler@frontlinemedcom.com
On Twitter @mitchelzoler
The best way to minimize death and disability in most patients having an acute ischemic stroke is rapid thrombolysis by infusion of tissue plasminogen activator. Mechanical clot removal – thrombectomy – has recently been shown even better, but it’s applicable to just a fraction of these stroke patients, and even for them thrombolysis remains, for the time being, the recommended first step, with thrombectomy following soon after.
The good news is that more eligible U.S. stroke patients than ever before get this effective treatment. As I reported recently from the International Stroke Conference, as of mid-2016, 68% of U.S. acute ischemic stroke patients treated at about 2,000 of the largest and most focused U.S. stroke hospitals received thrombolytic treatment within 60 minutes of their hospital arrival. That’s up from 30% in late 2009. Hooray! The sad news is that many eligible stroke patients seen at these hospitals don’t get treated this way. Simple math puts that figure at 32%. In other words, last year, nearly a third of U.S. stroke patients who should have received quick thrombolysis didn’t, even though they were taken to the country’s top stroke hospitals.
How do I know that more universal rapid thrombolysis is possible? The 2016 numbers reported from the Get With the Guidelines (GWTG)–Stroke hospitals showed that roughly 2% of the 788 hospitals included in this analysis treated 90% or more of their eligible stroke patients with thrombolysis within an hour. That’s about 16 hospitals. Another 8%, upward of 60 hospitals, treated 80%-89% of their eligible stroke patients within this window. So a high level of thrombolysis treatment is possible. It just isn’t being done everywhere. About 20% of the hospitals in the program treated 40% or fewer of eligible patients they saw within the 60-minute window.
I have no idea why some hospitals do so well while others don’t, despite being in the GWTG-Stroke program that promotes excellence in stroke care delivery. In the most recent iteration of the GWTG–Stroke Target Stroke program, phase II, the organization promoted 11 steps for hospitals to take to optimize rapid delivery of thrombolysis. The obvious inference is that some hospitals are doing all 11 steps very well and consistently, and many others aren’t. Underperforming hospitals owe it to their patients to do a much better job; the top-performing hospitals show it’s possible.
I have heard a lot recently at meetings about how research has established that a range of medical treatments, if used diligently by patients as directed, will substantially improve and prolong their life. Patient compliance then becomes a big issue, and so now I’m hearing more about new approaches to improve compliance. But what about hospital compliance?
Treating acute ischemic stroke as well as possible is different from most disorders – it’s not about patient compliance. It’s about the ambulance that picks up the patient and the hospital where the patient gets taken. The success or failure of the acute treatment that the roughly 700,000 annual U.S. acute ischemic stroke patients receive lies entirely in the hands of the hospital staff. Fewer than 10% of U.S. stroke hospitals offer the vast majority of these patients the best care currently available. Many others don’t do as well, and a huge fraction remain woefully slow, even though everyone knows the pathway to doing better. Underperforming hospitals owe it to patients to up their game, and they need to start doing it now.
mzoler@frontlinemedcom.com
On Twitter @mitchelzoler
New-onset AF boosts bad HFrEF outcomes
WASHINGTON – New onset atrial fibrillation more than doubled the rate of adverse outcomes in patients with heart failure with reduced ejection fraction in a review of more than 15,000 such patients.
In 9,934 patients with heart failure with reduced ejection fraction (HFrEF) and no history of atrial fibrillation (AF), development of new-onset AF was linked with a greater than twofold increased risk of cardiovascular disease death or hospitalization for heart failure during follow-up, compared with HFrEF patients who did not initially have or later develop heart failure, after adjustment for several demographic and clinical variables, John J.V. McMurray, MD, said at the annual meeting of the American College of Cardiology. This difference for the primary endpoint of his analysis was statistically significant.
The 1,645 patients with paroxysmal AF at the start of their follow-up also had a significantly increased rate of cardiovascular death or heart failure hospitalization, but their increased risk when compared with HFrEF patients who didn’t develop AF was a much more modest 20% in his fully adjusted analysis. The patients who began follow-up with paroxysmal AF also had a relatively increased relative stroke rate of 33% when compared with HFrEF patients without AF at baseline who remained AF free, but the all-cause mortality rate among those with paroxysmal AF wasn’t significantly elevated, compared with the comparator group.
The 3,770 patients with persistent or permanent AF at baseline showed no statistically significant spike in their adverse event rates, compared with patients without AF, for any of the examined endpoints. The study group also included 66 patients with an undefined form of AF who weren’t included in these analyses.
“It’s the first episodes and paroxysmal episodes that cause trouble, and the trouble they cause is stroke,” Dr. McMurray said in an interview. Their stroke risk gets exacerbated in clinical practice, because these patients often don’t receive the stroke prevention they need in the form of anticoagulation treatment.
“We find over and over that patients with paroxysmal AF are not anticoagulated as frequently as they should be,” Dr. McMurray said. And HFrEF patients with a first AF episode need anticoagulation, too, as soon as AF is diagnosed, he advised.
He went a step further and speculated that the reason why HFrEF patients with new onset AF did so poorly in his analysis was because they already had several prior, brief AF episodes that had gone undetected. “Many of these patients probably had undiagnosed, clinically unapparent AF episodes” that then resulted in strokes, he suggested.
The upshot is that patients with HFrEF may need more aggressive monitoring for new-onset AF, possibly in the form of small, implanted arrhythmia-detection devices. Dr. McMurray said that he and other researchers are currently testing whether this hypothesis is correct. “We and others are now looking at this because these new data are convincing that new-onset AF is bad news [for HFrEF patients].”
In the analysis, “we looked only at clinically recognized and adjudicated new-onset AF. Goodness knows how many HFrEF patients are having unrecognized paroxysmal AF. Almost certainly there is a lot that is unrecognized” that potentially could be detected using a small implanted arrhythmia monitor, which could then lead to earlier anticoagulant treatment as well as possible treatment with antiarrhythmic drugs or with catheter ablation, Dr. McMurray said. Looking for undetected AF in HFrEF patients “is where the science is moving.”
The findings that Dr. McMurray reported are “something we should act on,” commented Adrian F. Hernandez, MD, professor of medicine and a cardiologist at Duke University in Durham, N.C. The comorbidity of AF in HFrEF patients requires “aggressive anticoagulation, and also a review of their heart failure medical treatment to be sure that is optimized, because AF could be a sign of worsening heart failure,” Dr. Hernandez said in an interview. “We may need to more aggressively get HFrEF patients with AF into normal sinus rhythm.”
When Mikhail Kosiborod, MD, treats HFrEF patients with a high risk for AF, such as patients with lower ejection fractions, a dilated left ventricle, or a dilated atrium, “I frequently do 30-day loop recordings in these patients because of their risk for incident AF,” Dr. Kosiborod said in an interview. “We don’t yet have convincing evidence for this, but it makes sense.”
Another finding from his analysis was that the HFrEF patients enrolled in these two trials did not get treatment with a mineralocorticoid receptor antagonist – spironolactone or eplerenone – “as often as they should,” with treatment rates of 44%-48%, compared with use of a beta-blocker in 92%-95% of patients. Treatment with eplerenone (Inspra) “has been shown to reduce the risk for new onset AF, so adding eplerenone or spironolactone is an important step that could be taken to try to prevent AF as well as treat the HFrEF and reduce mortality,” Dr. McMurray said.
PARADIGM-HF and ATMOSPHERE were funded by Novartis. Dr. McMurray has been a consultant to and has received travel and research support from Novartis, and he has received research and travel support from Amgen. Dr. Hernandez has received honoraria from Amgen, AstraZeneca, Janssen, Merck, and Novartis, and has received research support from Amgen, Bayer, Merck, and Portola. Dr. Kosiborod has been a consultant to several drug companies, and he has received research funding from AstraZeneca, Boehringer Ingelheim, Gilead, and Sanofi-Aventis.
mzoler@frontlinemedcom.com
On Twitter @mitchelzoler
WASHINGTON – New onset atrial fibrillation more than doubled the rate of adverse outcomes in patients with heart failure with reduced ejection fraction in a review of more than 15,000 such patients.
In 9,934 patients with heart failure with reduced ejection fraction (HFrEF) and no history of atrial fibrillation (AF), development of new-onset AF was linked with a greater than twofold increased risk of cardiovascular disease death or hospitalization for heart failure during follow-up, compared with HFrEF patients who did not initially have or later develop heart failure, after adjustment for several demographic and clinical variables, John J.V. McMurray, MD, said at the annual meeting of the American College of Cardiology. This difference for the primary endpoint of his analysis was statistically significant.
The 1,645 patients with paroxysmal AF at the start of their follow-up also had a significantly increased rate of cardiovascular death or heart failure hospitalization, but their increased risk when compared with HFrEF patients who didn’t develop AF was a much more modest 20% in his fully adjusted analysis. The patients who began follow-up with paroxysmal AF also had a relatively increased relative stroke rate of 33% when compared with HFrEF patients without AF at baseline who remained AF free, but the all-cause mortality rate among those with paroxysmal AF wasn’t significantly elevated, compared with the comparator group.
The 3,770 patients with persistent or permanent AF at baseline showed no statistically significant spike in their adverse event rates, compared with patients without AF, for any of the examined endpoints. The study group also included 66 patients with an undefined form of AF who weren’t included in these analyses.
“It’s the first episodes and paroxysmal episodes that cause trouble, and the trouble they cause is stroke,” Dr. McMurray said in an interview. Their stroke risk gets exacerbated in clinical practice, because these patients often don’t receive the stroke prevention they need in the form of anticoagulation treatment.
“We find over and over that patients with paroxysmal AF are not anticoagulated as frequently as they should be,” Dr. McMurray said. And HFrEF patients with a first AF episode need anticoagulation, too, as soon as AF is diagnosed, he advised.
He went a step further and speculated that the reason why HFrEF patients with new onset AF did so poorly in his analysis was because they already had several prior, brief AF episodes that had gone undetected. “Many of these patients probably had undiagnosed, clinically unapparent AF episodes” that then resulted in strokes, he suggested.
The upshot is that patients with HFrEF may need more aggressive monitoring for new-onset AF, possibly in the form of small, implanted arrhythmia-detection devices. Dr. McMurray said that he and other researchers are currently testing whether this hypothesis is correct. “We and others are now looking at this because these new data are convincing that new-onset AF is bad news [for HFrEF patients].”
In the analysis, “we looked only at clinically recognized and adjudicated new-onset AF. Goodness knows how many HFrEF patients are having unrecognized paroxysmal AF. Almost certainly there is a lot that is unrecognized” that potentially could be detected using a small implanted arrhythmia monitor, which could then lead to earlier anticoagulant treatment as well as possible treatment with antiarrhythmic drugs or with catheter ablation, Dr. McMurray said. Looking for undetected AF in HFrEF patients “is where the science is moving.”
The findings that Dr. McMurray reported are “something we should act on,” commented Adrian F. Hernandez, MD, professor of medicine and a cardiologist at Duke University in Durham, N.C. The comorbidity of AF in HFrEF patients requires “aggressive anticoagulation, and also a review of their heart failure medical treatment to be sure that is optimized, because AF could be a sign of worsening heart failure,” Dr. Hernandez said in an interview. “We may need to more aggressively get HFrEF patients with AF into normal sinus rhythm.”
When Mikhail Kosiborod, MD, treats HFrEF patients with a high risk for AF, such as patients with lower ejection fractions, a dilated left ventricle, or a dilated atrium, “I frequently do 30-day loop recordings in these patients because of their risk for incident AF,” Dr. Kosiborod said in an interview. “We don’t yet have convincing evidence for this, but it makes sense.”
Another finding from his analysis was that the HFrEF patients enrolled in these two trials did not get treatment with a mineralocorticoid receptor antagonist – spironolactone or eplerenone – “as often as they should,” with treatment rates of 44%-48%, compared with use of a beta-blocker in 92%-95% of patients. Treatment with eplerenone (Inspra) “has been shown to reduce the risk for new onset AF, so adding eplerenone or spironolactone is an important step that could be taken to try to prevent AF as well as treat the HFrEF and reduce mortality,” Dr. McMurray said.
PARADIGM-HF and ATMOSPHERE were funded by Novartis. Dr. McMurray has been a consultant to and has received travel and research support from Novartis, and he has received research and travel support from Amgen. Dr. Hernandez has received honoraria from Amgen, AstraZeneca, Janssen, Merck, and Novartis, and has received research support from Amgen, Bayer, Merck, and Portola. Dr. Kosiborod has been a consultant to several drug companies, and he has received research funding from AstraZeneca, Boehringer Ingelheim, Gilead, and Sanofi-Aventis.
mzoler@frontlinemedcom.com
On Twitter @mitchelzoler
WASHINGTON – New onset atrial fibrillation more than doubled the rate of adverse outcomes in patients with heart failure with reduced ejection fraction in a review of more than 15,000 such patients.
In 9,934 patients with heart failure with reduced ejection fraction (HFrEF) and no history of atrial fibrillation (AF), development of new-onset AF was linked with a greater than twofold increased risk of cardiovascular disease death or hospitalization for heart failure during follow-up, compared with HFrEF patients who did not initially have or later develop heart failure, after adjustment for several demographic and clinical variables, John J.V. McMurray, MD, said at the annual meeting of the American College of Cardiology. This difference for the primary endpoint of his analysis was statistically significant.
The 1,645 patients with paroxysmal AF at the start of their follow-up also had a significantly increased rate of cardiovascular death or heart failure hospitalization, but their increased risk when compared with HFrEF patients who didn’t develop AF was a much more modest 20% in his fully adjusted analysis. The patients who began follow-up with paroxysmal AF also had a relatively increased relative stroke rate of 33% when compared with HFrEF patients without AF at baseline who remained AF free, but the all-cause mortality rate among those with paroxysmal AF wasn’t significantly elevated, compared with the comparator group.
The 3,770 patients with persistent or permanent AF at baseline showed no statistically significant spike in their adverse event rates, compared with patients without AF, for any of the examined endpoints. The study group also included 66 patients with an undefined form of AF who weren’t included in these analyses.
“It’s the first episodes and paroxysmal episodes that cause trouble, and the trouble they cause is stroke,” Dr. McMurray said in an interview. Their stroke risk gets exacerbated in clinical practice, because these patients often don’t receive the stroke prevention they need in the form of anticoagulation treatment.
“We find over and over that patients with paroxysmal AF are not anticoagulated as frequently as they should be,” Dr. McMurray said. And HFrEF patients with a first AF episode need anticoagulation, too, as soon as AF is diagnosed, he advised.
He went a step further and speculated that the reason why HFrEF patients with new onset AF did so poorly in his analysis was because they already had several prior, brief AF episodes that had gone undetected. “Many of these patients probably had undiagnosed, clinically unapparent AF episodes” that then resulted in strokes, he suggested.
The upshot is that patients with HFrEF may need more aggressive monitoring for new-onset AF, possibly in the form of small, implanted arrhythmia-detection devices. Dr. McMurray said that he and other researchers are currently testing whether this hypothesis is correct. “We and others are now looking at this because these new data are convincing that new-onset AF is bad news [for HFrEF patients].”
In the analysis, “we looked only at clinically recognized and adjudicated new-onset AF. Goodness knows how many HFrEF patients are having unrecognized paroxysmal AF. Almost certainly there is a lot that is unrecognized” that potentially could be detected using a small implanted arrhythmia monitor, which could then lead to earlier anticoagulant treatment as well as possible treatment with antiarrhythmic drugs or with catheter ablation, Dr. McMurray said. Looking for undetected AF in HFrEF patients “is where the science is moving.”
The findings that Dr. McMurray reported are “something we should act on,” commented Adrian F. Hernandez, MD, professor of medicine and a cardiologist at Duke University in Durham, N.C. The comorbidity of AF in HFrEF patients requires “aggressive anticoagulation, and also a review of their heart failure medical treatment to be sure that is optimized, because AF could be a sign of worsening heart failure,” Dr. Hernandez said in an interview. “We may need to more aggressively get HFrEF patients with AF into normal sinus rhythm.”
When Mikhail Kosiborod, MD, treats HFrEF patients with a high risk for AF, such as patients with lower ejection fractions, a dilated left ventricle, or a dilated atrium, “I frequently do 30-day loop recordings in these patients because of their risk for incident AF,” Dr. Kosiborod said in an interview. “We don’t yet have convincing evidence for this, but it makes sense.”
Another finding from his analysis was that the HFrEF patients enrolled in these two trials did not get treatment with a mineralocorticoid receptor antagonist – spironolactone or eplerenone – “as often as they should,” with treatment rates of 44%-48%, compared with use of a beta-blocker in 92%-95% of patients. Treatment with eplerenone (Inspra) “has been shown to reduce the risk for new onset AF, so adding eplerenone or spironolactone is an important step that could be taken to try to prevent AF as well as treat the HFrEF and reduce mortality,” Dr. McMurray said.
PARADIGM-HF and ATMOSPHERE were funded by Novartis. Dr. McMurray has been a consultant to and has received travel and research support from Novartis, and he has received research and travel support from Amgen. Dr. Hernandez has received honoraria from Amgen, AstraZeneca, Janssen, Merck, and Novartis, and has received research support from Amgen, Bayer, Merck, and Portola. Dr. Kosiborod has been a consultant to several drug companies, and he has received research funding from AstraZeneca, Boehringer Ingelheim, Gilead, and Sanofi-Aventis.
mzoler@frontlinemedcom.com
On Twitter @mitchelzoler
AT ACC 17
Key clinical point:
Major finding: Adverse outcomes were more than twice as frequent in HFrEF patients with incident atrial fibrillation, compared with those without AF.
Data source: Post hoc analysis of 15,415 heart failure patients enrolled in the PARADIGM-HF and ATMOSPHERE trials.
Disclosures: PARADIGM-HF and ATMOSPHERE were funded by Novartis. Dr. McMurray has been a consultant to and has received travel and research support from Novartis, and he has received research and travel support from Amgen.
Gliflozins’ heart failure protection in type 2 diabetes confirmed
WASHINGTON – The remarkable and unexpected findings first reported from the EMPA-REG OUTCOME trial in late 2015 – that treatment of type 2 diabetes patients with the SGLT-2 inhibitor empagliflozin led to significantly reduced rates of heart failure hospitalization and all-cause death – received its first major confirmation in an analysis of observational data collected from more than 300,000 patients with type 2 diabetes treated in six countries including the United States.
The new findings also, for the first time, extended the EMPA-REG OUTCOME results (N Engl J Med. 2015 Nov 26;373[22]:2117-28) beyond empagliflozin with evidence that the heart failure and mortality benefit also occurred with other drugs from the sodium glucose cotransporter–2 (SGLT-2) inhibitor class, specifically canagliflozin and dapagliflozin, Mikhail Kosiborod, MD, said at the annual meeting of the American College of Cardiology.
The analysis showed that type 2 diabetes patients who were newly started on treatment with one of these SGLT-2 inhibitors had during follow-up a 39% reduced rate of heart failure hospitalizations, a 51% reduced mortality rate, and a 46% reduced rate of the combined endpoint of heart failure hospitalization or death, compared with patients treated with any other type of oral glucose-lowering drug, reported Dr. Kosiborod. The risk reductions were “remarkably similar to those seen in EMPA-REG OUTCOME,” he noted.
The findings address three “key questions” raised by the EMPA-REG OUTCOME results, Dr. Kosiborod, a cardiologist and professor of medicine at Saint Luke’s Mid America Heart Institute in Kansas City, Mo., said in an interview:
• Is this a class effect? The data “seem to suggest that the benefits seen in the EMPA-REG OUTCOME study are likely a class effect.” The study population of 154,523 patients in the heart failure hospitalization analysis who began treatment with an SGLT-2 inhibitor included 53% who received canagliflozin (Invokana), 42% who received dapagliflozin (Farxiga), and 6% who received empagliflozin (Jardiance) (percentages total 101% because of rounding). Dr. Kosiborod also highlighted that within several of the six countries that contributed data to this analysis – the United States, Denmark, Germany, Norway, Sweden, and the United Kingdom – the percentages of patients on each of these three drugs varied substantially, but despite that the relative reduced risks for heart failure hospitalization and mortality were roughly the same within each country, giving further credence to the notion that a class effect exists.
• Do lower-risk patients benefit? “The benefits of SGLT-2 inhibitor treatment appeared to extend to lower risk patients” than those enrolled in EMPA-REG OUTCOME. In the randomized trial, which enrolled 7,028 patients, more than 99% had established cardiovascular disease. In the new analysis patients had a 13% prevalence of any cardiovascular disease at baseline, and the prevalence of heart failure was 3%.
• Is this relevant to clinical practice? Unlike the highly selected patients entered in the EMPA-REG OUTCOME trial, the patients started on an SGLT-2 inhibitor in the observational study were unselected and came from routine practice situations, “suggesting that the benefits seen in EMPA-REG OUTCOME translate into real-world clinical practice,” Dr. Kosiborod said. “With these data we see for the first time in a large number of patients from multiple countries important evidence suggesting that the SGLT-2 inhibitors may provide in the real world a similar benefit to what was observed in EMPA-REG OUTCOME.”
“The lesson from Dr. Kosiborod’s study is that among patients with type 2 diabetes, treatment with an SGLT-2 inhibitor seems to result in lowered rates of heart failure hospitalizations and mortality, and it’s a safe class of drugs. In the past, we worried about worsening heart failure in patients at risk for developing heart failure” such as patients with type 2 diabetes, said Adrian F. Hernandez, MD, professor of medicine and a cardiologist at Duke University in Durham, N.C. The new data make it seem like using an SGLT-2 inhibitor to treat patients with type 2 diabetes “is an appropriate strategy.” But Dr. Hernandez added that in his opinion metformin remains the top drug for type 2 diabetes, while SGLT-2 inhibitors are now “the next drug class to add,” he said in an interview.
Dr. Kosiborod had a somewhat different take. “If a patient with type 2 diabetes did not want to enter a trial or couldn’t get into a trial and fit the profile of a patient who could benefit, I would absolutely treat that patient with an SGLT-2 inhibitor. I’m using these medications clinically as a cardiologist,” he said. “Treatments that have significant benefits for important outcomes should be prioritized over treatments that may reduce hemoglobin A1c but do not have similar benefits.”
The CVD-REAL (Comparative Effectiveness of Cardiovascular Outcomes in New Users of SGLT-2 Inhibitors) study used data from adult, previously untreated patients with type 2 diabetes in national registries from the five included European countries. U.S. data were from the Truven Health MarketScan database and from Medicare. This produced a total pool of 160,010 patients who began treatment on an SGLT-2 inhibitor and 1,139,905 patients who began treatment with another oral antidiabetes drug.
Dr. Kosiborod and his associates then performed propensity-score matching to identify 154,523 patients started on an SGLT-2 inhibitor who each closely matched a patient from the other subgroup for baseline demographic and clinical features, producing an analysis dataset of just over 309,000 matched patients. The average age of the included patients was 57 years; 45% were women. During follow-up, 961 patients had a heart failure hospitalization and 1,334 patients died.
Dr. Kosiborod noted that while a potential limitation to his findings is residual confounding not eliminated by the propensity score matching, he was confident about the results because the incidence of other outcomes not expected to be influenced by treatment with SGLT-2 inhibitors were similar in the two study subgroups, suggesting that the linkages between the kind of drug used and differences in heart failure hospitalization rates and in mortality weren’t spurious.
“If there was residual confounding, you’d expect to see similar associations for other endpoints, which we didn’t see,” he said. In addition, the heart failure hospitalization rate differences seen between the SGLT-2 inhibitor recipients and the other patients were consistent in a trio of sensitivity analyses, further buttressing the findings’ plausibility.
CVD-REAL was sponsored by AstraZeneca, the company that markets dapagliflozin (Farxiga). Dr. Kosiborod has been a consultant to and/or received research funding from AstraZeneca, Boehringer Ingelheim, Sanofi-Aventis and Gilead. Dr. Hernandez has received honoraria and/or research support from AstraZeneca, Amgen, Janssen, Merck, Novartis, and Portola. Several of the coauthors on the CVD-REAL study were AstraZeneca employees.
mzoler@frontlinemedcom.com
On Twitter @mitchelzoler
WASHINGTON – The remarkable and unexpected findings first reported from the EMPA-REG OUTCOME trial in late 2015 – that treatment of type 2 diabetes patients with the SGLT-2 inhibitor empagliflozin led to significantly reduced rates of heart failure hospitalization and all-cause death – received its first major confirmation in an analysis of observational data collected from more than 300,000 patients with type 2 diabetes treated in six countries including the United States.
The new findings also, for the first time, extended the EMPA-REG OUTCOME results (N Engl J Med. 2015 Nov 26;373[22]:2117-28) beyond empagliflozin with evidence that the heart failure and mortality benefit also occurred with other drugs from the sodium glucose cotransporter–2 (SGLT-2) inhibitor class, specifically canagliflozin and dapagliflozin, Mikhail Kosiborod, MD, said at the annual meeting of the American College of Cardiology.
The analysis showed that type 2 diabetes patients who were newly started on treatment with one of these SGLT-2 inhibitors had during follow-up a 39% reduced rate of heart failure hospitalizations, a 51% reduced mortality rate, and a 46% reduced rate of the combined endpoint of heart failure hospitalization or death, compared with patients treated with any other type of oral glucose-lowering drug, reported Dr. Kosiborod. The risk reductions were “remarkably similar to those seen in EMPA-REG OUTCOME,” he noted.
The findings address three “key questions” raised by the EMPA-REG OUTCOME results, Dr. Kosiborod, a cardiologist and professor of medicine at Saint Luke’s Mid America Heart Institute in Kansas City, Mo., said in an interview:
• Is this a class effect? The data “seem to suggest that the benefits seen in the EMPA-REG OUTCOME study are likely a class effect.” The study population of 154,523 patients in the heart failure hospitalization analysis who began treatment with an SGLT-2 inhibitor included 53% who received canagliflozin (Invokana), 42% who received dapagliflozin (Farxiga), and 6% who received empagliflozin (Jardiance) (percentages total 101% because of rounding). Dr. Kosiborod also highlighted that within several of the six countries that contributed data to this analysis – the United States, Denmark, Germany, Norway, Sweden, and the United Kingdom – the percentages of patients on each of these three drugs varied substantially, but despite that the relative reduced risks for heart failure hospitalization and mortality were roughly the same within each country, giving further credence to the notion that a class effect exists.
• Do lower-risk patients benefit? “The benefits of SGLT-2 inhibitor treatment appeared to extend to lower risk patients” than those enrolled in EMPA-REG OUTCOME. In the randomized trial, which enrolled 7,028 patients, more than 99% had established cardiovascular disease. In the new analysis patients had a 13% prevalence of any cardiovascular disease at baseline, and the prevalence of heart failure was 3%.
• Is this relevant to clinical practice? Unlike the highly selected patients entered in the EMPA-REG OUTCOME trial, the patients started on an SGLT-2 inhibitor in the observational study were unselected and came from routine practice situations, “suggesting that the benefits seen in EMPA-REG OUTCOME translate into real-world clinical practice,” Dr. Kosiborod said. “With these data we see for the first time in a large number of patients from multiple countries important evidence suggesting that the SGLT-2 inhibitors may provide in the real world a similar benefit to what was observed in EMPA-REG OUTCOME.”
“The lesson from Dr. Kosiborod’s study is that among patients with type 2 diabetes, treatment with an SGLT-2 inhibitor seems to result in lowered rates of heart failure hospitalizations and mortality, and it’s a safe class of drugs. In the past, we worried about worsening heart failure in patients at risk for developing heart failure” such as patients with type 2 diabetes, said Adrian F. Hernandez, MD, professor of medicine and a cardiologist at Duke University in Durham, N.C. The new data make it seem like using an SGLT-2 inhibitor to treat patients with type 2 diabetes “is an appropriate strategy.” But Dr. Hernandez added that in his opinion metformin remains the top drug for type 2 diabetes, while SGLT-2 inhibitors are now “the next drug class to add,” he said in an interview.
Dr. Kosiborod had a somewhat different take. “If a patient with type 2 diabetes did not want to enter a trial or couldn’t get into a trial and fit the profile of a patient who could benefit, I would absolutely treat that patient with an SGLT-2 inhibitor. I’m using these medications clinically as a cardiologist,” he said. “Treatments that have significant benefits for important outcomes should be prioritized over treatments that may reduce hemoglobin A1c but do not have similar benefits.”
The CVD-REAL (Comparative Effectiveness of Cardiovascular Outcomes in New Users of SGLT-2 Inhibitors) study used data from adult, previously untreated patients with type 2 diabetes in national registries from the five included European countries. U.S. data were from the Truven Health MarketScan database and from Medicare. This produced a total pool of 160,010 patients who began treatment on an SGLT-2 inhibitor and 1,139,905 patients who began treatment with another oral antidiabetes drug.
Dr. Kosiborod and his associates then performed propensity-score matching to identify 154,523 patients started on an SGLT-2 inhibitor who each closely matched a patient from the other subgroup for baseline demographic and clinical features, producing an analysis dataset of just over 309,000 matched patients. The average age of the included patients was 57 years; 45% were women. During follow-up, 961 patients had a heart failure hospitalization and 1,334 patients died.
Dr. Kosiborod noted that while a potential limitation to his findings is residual confounding not eliminated by the propensity score matching, he was confident about the results because the incidence of other outcomes not expected to be influenced by treatment with SGLT-2 inhibitors were similar in the two study subgroups, suggesting that the linkages between the kind of drug used and differences in heart failure hospitalization rates and in mortality weren’t spurious.
“If there was residual confounding, you’d expect to see similar associations for other endpoints, which we didn’t see,” he said. In addition, the heart failure hospitalization rate differences seen between the SGLT-2 inhibitor recipients and the other patients were consistent in a trio of sensitivity analyses, further buttressing the findings’ plausibility.
CVD-REAL was sponsored by AstraZeneca, the company that markets dapagliflozin (Farxiga). Dr. Kosiborod has been a consultant to and/or received research funding from AstraZeneca, Boehringer Ingelheim, Sanofi-Aventis and Gilead. Dr. Hernandez has received honoraria and/or research support from AstraZeneca, Amgen, Janssen, Merck, Novartis, and Portola. Several of the coauthors on the CVD-REAL study were AstraZeneca employees.
mzoler@frontlinemedcom.com
On Twitter @mitchelzoler
WASHINGTON – The remarkable and unexpected findings first reported from the EMPA-REG OUTCOME trial in late 2015 – that treatment of type 2 diabetes patients with the SGLT-2 inhibitor empagliflozin led to significantly reduced rates of heart failure hospitalization and all-cause death – received its first major confirmation in an analysis of observational data collected from more than 300,000 patients with type 2 diabetes treated in six countries including the United States.
The new findings also, for the first time, extended the EMPA-REG OUTCOME results (N Engl J Med. 2015 Nov 26;373[22]:2117-28) beyond empagliflozin with evidence that the heart failure and mortality benefit also occurred with other drugs from the sodium glucose cotransporter–2 (SGLT-2) inhibitor class, specifically canagliflozin and dapagliflozin, Mikhail Kosiborod, MD, said at the annual meeting of the American College of Cardiology.
The analysis showed that type 2 diabetes patients who were newly started on treatment with one of these SGLT-2 inhibitors had during follow-up a 39% reduced rate of heart failure hospitalizations, a 51% reduced mortality rate, and a 46% reduced rate of the combined endpoint of heart failure hospitalization or death, compared with patients treated with any other type of oral glucose-lowering drug, reported Dr. Kosiborod. The risk reductions were “remarkably similar to those seen in EMPA-REG OUTCOME,” he noted.
The findings address three “key questions” raised by the EMPA-REG OUTCOME results, Dr. Kosiborod, a cardiologist and professor of medicine at Saint Luke’s Mid America Heart Institute in Kansas City, Mo., said in an interview:
• Is this a class effect? The data “seem to suggest that the benefits seen in the EMPA-REG OUTCOME study are likely a class effect.” The study population of 154,523 patients in the heart failure hospitalization analysis who began treatment with an SGLT-2 inhibitor included 53% who received canagliflozin (Invokana), 42% who received dapagliflozin (Farxiga), and 6% who received empagliflozin (Jardiance) (percentages total 101% because of rounding). Dr. Kosiborod also highlighted that within several of the six countries that contributed data to this analysis – the United States, Denmark, Germany, Norway, Sweden, and the United Kingdom – the percentages of patients on each of these three drugs varied substantially, but despite that the relative reduced risks for heart failure hospitalization and mortality were roughly the same within each country, giving further credence to the notion that a class effect exists.
• Do lower-risk patients benefit? “The benefits of SGLT-2 inhibitor treatment appeared to extend to lower risk patients” than those enrolled in EMPA-REG OUTCOME. In the randomized trial, which enrolled 7,028 patients, more than 99% had established cardiovascular disease. In the new analysis patients had a 13% prevalence of any cardiovascular disease at baseline, and the prevalence of heart failure was 3%.
• Is this relevant to clinical practice? Unlike the highly selected patients entered in the EMPA-REG OUTCOME trial, the patients started on an SGLT-2 inhibitor in the observational study were unselected and came from routine practice situations, “suggesting that the benefits seen in EMPA-REG OUTCOME translate into real-world clinical practice,” Dr. Kosiborod said. “With these data we see for the first time in a large number of patients from multiple countries important evidence suggesting that the SGLT-2 inhibitors may provide in the real world a similar benefit to what was observed in EMPA-REG OUTCOME.”
“The lesson from Dr. Kosiborod’s study is that among patients with type 2 diabetes, treatment with an SGLT-2 inhibitor seems to result in lowered rates of heart failure hospitalizations and mortality, and it’s a safe class of drugs. In the past, we worried about worsening heart failure in patients at risk for developing heart failure” such as patients with type 2 diabetes, said Adrian F. Hernandez, MD, professor of medicine and a cardiologist at Duke University in Durham, N.C. The new data make it seem like using an SGLT-2 inhibitor to treat patients with type 2 diabetes “is an appropriate strategy.” But Dr. Hernandez added that in his opinion metformin remains the top drug for type 2 diabetes, while SGLT-2 inhibitors are now “the next drug class to add,” he said in an interview.
Dr. Kosiborod had a somewhat different take. “If a patient with type 2 diabetes did not want to enter a trial or couldn’t get into a trial and fit the profile of a patient who could benefit, I would absolutely treat that patient with an SGLT-2 inhibitor. I’m using these medications clinically as a cardiologist,” he said. “Treatments that have significant benefits for important outcomes should be prioritized over treatments that may reduce hemoglobin A1c but do not have similar benefits.”
The CVD-REAL (Comparative Effectiveness of Cardiovascular Outcomes in New Users of SGLT-2 Inhibitors) study used data from adult, previously untreated patients with type 2 diabetes in national registries from the five included European countries. U.S. data were from the Truven Health MarketScan database and from Medicare. This produced a total pool of 160,010 patients who began treatment on an SGLT-2 inhibitor and 1,139,905 patients who began treatment with another oral antidiabetes drug.
Dr. Kosiborod and his associates then performed propensity-score matching to identify 154,523 patients started on an SGLT-2 inhibitor who each closely matched a patient from the other subgroup for baseline demographic and clinical features, producing an analysis dataset of just over 309,000 matched patients. The average age of the included patients was 57 years; 45% were women. During follow-up, 961 patients had a heart failure hospitalization and 1,334 patients died.
Dr. Kosiborod noted that while a potential limitation to his findings is residual confounding not eliminated by the propensity score matching, he was confident about the results because the incidence of other outcomes not expected to be influenced by treatment with SGLT-2 inhibitors were similar in the two study subgroups, suggesting that the linkages between the kind of drug used and differences in heart failure hospitalization rates and in mortality weren’t spurious.
“If there was residual confounding, you’d expect to see similar associations for other endpoints, which we didn’t see,” he said. In addition, the heart failure hospitalization rate differences seen between the SGLT-2 inhibitor recipients and the other patients were consistent in a trio of sensitivity analyses, further buttressing the findings’ plausibility.
CVD-REAL was sponsored by AstraZeneca, the company that markets dapagliflozin (Farxiga). Dr. Kosiborod has been a consultant to and/or received research funding from AstraZeneca, Boehringer Ingelheim, Sanofi-Aventis and Gilead. Dr. Hernandez has received honoraria and/or research support from AstraZeneca, Amgen, Janssen, Merck, Novartis, and Portola. Several of the coauthors on the CVD-REAL study were AstraZeneca employees.
mzoler@frontlinemedcom.com
On Twitter @mitchelzoler
AT ACC 17
Key clinical point:
Major finding: Treatment with an SGLT-2 inhibitor was associated with a significant 39% reduction in heart failure hospitalizations compared with other antidiabetes drugs.
Data source: CVD-REAL, which used observational data collected from 309,046 patients with type 2 diabetes in six countries.
Disclosures: CVD-REAL was sponsored by AstraZeneca, the company that markets dapagliflozin (Farxiga). Dr. Kosiborod has been a consultant to AstraZeneca and to several other drug companies, and he has received research funding from AstraZeneca, Boehringer Ingelheim, Sanofi-Aventis and Gilead. Dr. Hernandez has received honoraria and research support from AstraZeneca and has also received honoraria from Amgen, Janssen, Merck, and Novartis, and has also received research support from Amgen, Bayer, Merck, and Portola. Several of the coauthors on the CVD-REAL study were AstraZeneca employees.