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What drives readmissions within 90 days after MI hospitalization
WASHINGTON – In a large population of Medicare patients hospitalized for acute MI, four factors stood out as predictors of increased likelihood of readmission within 90 days, Aaron D. Kugelmass, MD, reported at the annual meeting of the American College of Cardiology.
These four predictors of 90-day readmission were end-stage renal disease at the time of the initial admission for MI, which in a logistic regression model was independently associated with an 88% relative increase in readmission risk; no percutaneous coronary intervention (PCI) during the index hospitalization, which carried a 64% increase in risk; type 1 diabetes, with a 57% increased readmission rate; and heart failure at the initial hospitalization, with an associated 34% greater risk, according to Dr. Kugelmass, chief of cardiology and medical director of the heart and vascular center at Baystate Medical Center in Springfield, Mass.
“This is going to be a learning curve for everyone,” he said.
“The best way to deal with this change is to understand the factors driving costs and morbidity and mortality,” Dr. Kugelmass said, in explaining why he conducted a retrospective study of readmissions within 90 days in a population of 143,286 Medicare beneficiaries hospitalized for acute MI in 2014. The study focus was on readmissions because they add so much to total cost of care for a 90-day episode.
Twenty-eight percent of patients were readmitted at least once within 90 days of discharge following their acute MI. The Medicare bundled payment plan divides MI patients into two separate groups: those who undergo PCI during their initial hospitalization and those who receive medical management only. Thirty-one percent of the readmitted patients in Dr. Kugelmass’s study had undergone PCI during their index hospitalization, while the other 69% were managed medically.
Heart failure was the No. 1 reason for readmission within 90 days in patients who had PCI during the index hospitalization. It was the primary reason for 17.6% of readmissions. Next came recurrent angina or chest pain, which accounted for 6.6% of readmissions; chronic obstructive pulmonary disease or pneumonia, 6.3%; and GI bleeding with hemorrhage, which was the primary reason for 6.0% of readmissions. Together these four causes accounted for more than 36% of all readmissions in the PCI group.
“The GI bleeding data were really interesting,” the cardiologist said. “There’s a lot of talk now about reducing the duration of dual-antiplatelet therapy [DAPT] after PCI. This is an administrative data set that’s quite large, and it shows that GI bleeding in a post-PCI group early in the duration of DAPT is in fact a significant cause of readmission and poses significant hazard.”
Among patients who were medically managed during their index hospitalization, the top four reasons for readmission were heart failure, accounting for 20.6% of readmissions; cardiac surgery, 13.5%; sepsis, 7.8%; and chronic obstructive pulmonary disease/pneumonia, 6.3%. GI bleeding wasn’t a significant cause of readmission in this group.
“I think what we need to do next is dive deeper into the medically managed group. There is a cohort in there that’s incredibly sick and are likely to drive costs and be prone to readmission. And there’s another component of the medically managed group that had to be fairly healthy because they were able to undergo coronary artery bypass surgery within 90 days,” Dr. Kugelmass said.
He reported having no financial conflicts regarding his study.
WASHINGTON – In a large population of Medicare patients hospitalized for acute MI, four factors stood out as predictors of increased likelihood of readmission within 90 days, Aaron D. Kugelmass, MD, reported at the annual meeting of the American College of Cardiology.
These four predictors of 90-day readmission were end-stage renal disease at the time of the initial admission for MI, which in a logistic regression model was independently associated with an 88% relative increase in readmission risk; no percutaneous coronary intervention (PCI) during the index hospitalization, which carried a 64% increase in risk; type 1 diabetes, with a 57% increased readmission rate; and heart failure at the initial hospitalization, with an associated 34% greater risk, according to Dr. Kugelmass, chief of cardiology and medical director of the heart and vascular center at Baystate Medical Center in Springfield, Mass.
“This is going to be a learning curve for everyone,” he said.
“The best way to deal with this change is to understand the factors driving costs and morbidity and mortality,” Dr. Kugelmass said, in explaining why he conducted a retrospective study of readmissions within 90 days in a population of 143,286 Medicare beneficiaries hospitalized for acute MI in 2014. The study focus was on readmissions because they add so much to total cost of care for a 90-day episode.
Twenty-eight percent of patients were readmitted at least once within 90 days of discharge following their acute MI. The Medicare bundled payment plan divides MI patients into two separate groups: those who undergo PCI during their initial hospitalization and those who receive medical management only. Thirty-one percent of the readmitted patients in Dr. Kugelmass’s study had undergone PCI during their index hospitalization, while the other 69% were managed medically.
Heart failure was the No. 1 reason for readmission within 90 days in patients who had PCI during the index hospitalization. It was the primary reason for 17.6% of readmissions. Next came recurrent angina or chest pain, which accounted for 6.6% of readmissions; chronic obstructive pulmonary disease or pneumonia, 6.3%; and GI bleeding with hemorrhage, which was the primary reason for 6.0% of readmissions. Together these four causes accounted for more than 36% of all readmissions in the PCI group.
“The GI bleeding data were really interesting,” the cardiologist said. “There’s a lot of talk now about reducing the duration of dual-antiplatelet therapy [DAPT] after PCI. This is an administrative data set that’s quite large, and it shows that GI bleeding in a post-PCI group early in the duration of DAPT is in fact a significant cause of readmission and poses significant hazard.”
Among patients who were medically managed during their index hospitalization, the top four reasons for readmission were heart failure, accounting for 20.6% of readmissions; cardiac surgery, 13.5%; sepsis, 7.8%; and chronic obstructive pulmonary disease/pneumonia, 6.3%. GI bleeding wasn’t a significant cause of readmission in this group.
“I think what we need to do next is dive deeper into the medically managed group. There is a cohort in there that’s incredibly sick and are likely to drive costs and be prone to readmission. And there’s another component of the medically managed group that had to be fairly healthy because they were able to undergo coronary artery bypass surgery within 90 days,” Dr. Kugelmass said.
He reported having no financial conflicts regarding his study.
WASHINGTON – In a large population of Medicare patients hospitalized for acute MI, four factors stood out as predictors of increased likelihood of readmission within 90 days, Aaron D. Kugelmass, MD, reported at the annual meeting of the American College of Cardiology.
These four predictors of 90-day readmission were end-stage renal disease at the time of the initial admission for MI, which in a logistic regression model was independently associated with an 88% relative increase in readmission risk; no percutaneous coronary intervention (PCI) during the index hospitalization, which carried a 64% increase in risk; type 1 diabetes, with a 57% increased readmission rate; and heart failure at the initial hospitalization, with an associated 34% greater risk, according to Dr. Kugelmass, chief of cardiology and medical director of the heart and vascular center at Baystate Medical Center in Springfield, Mass.
“This is going to be a learning curve for everyone,” he said.
“The best way to deal with this change is to understand the factors driving costs and morbidity and mortality,” Dr. Kugelmass said, in explaining why he conducted a retrospective study of readmissions within 90 days in a population of 143,286 Medicare beneficiaries hospitalized for acute MI in 2014. The study focus was on readmissions because they add so much to total cost of care for a 90-day episode.
Twenty-eight percent of patients were readmitted at least once within 90 days of discharge following their acute MI. The Medicare bundled payment plan divides MI patients into two separate groups: those who undergo PCI during their initial hospitalization and those who receive medical management only. Thirty-one percent of the readmitted patients in Dr. Kugelmass’s study had undergone PCI during their index hospitalization, while the other 69% were managed medically.
Heart failure was the No. 1 reason for readmission within 90 days in patients who had PCI during the index hospitalization. It was the primary reason for 17.6% of readmissions. Next came recurrent angina or chest pain, which accounted for 6.6% of readmissions; chronic obstructive pulmonary disease or pneumonia, 6.3%; and GI bleeding with hemorrhage, which was the primary reason for 6.0% of readmissions. Together these four causes accounted for more than 36% of all readmissions in the PCI group.
“The GI bleeding data were really interesting,” the cardiologist said. “There’s a lot of talk now about reducing the duration of dual-antiplatelet therapy [DAPT] after PCI. This is an administrative data set that’s quite large, and it shows that GI bleeding in a post-PCI group early in the duration of DAPT is in fact a significant cause of readmission and poses significant hazard.”
Among patients who were medically managed during their index hospitalization, the top four reasons for readmission were heart failure, accounting for 20.6% of readmissions; cardiac surgery, 13.5%; sepsis, 7.8%; and chronic obstructive pulmonary disease/pneumonia, 6.3%. GI bleeding wasn’t a significant cause of readmission in this group.
“I think what we need to do next is dive deeper into the medically managed group. There is a cohort in there that’s incredibly sick and are likely to drive costs and be prone to readmission. And there’s another component of the medically managed group that had to be fairly healthy because they were able to undergo coronary artery bypass surgery within 90 days,” Dr. Kugelmass said.
He reported having no financial conflicts regarding his study.
Key clinical point:
Major finding: Twenty-eight percent of Medicare patients hospitalized for acute MI were readmitted within 90 days.
Data source: A retrospective study of readmissions within 90 days among more than 143,000 Medicare beneficiaries hospitalized for acute MI in 2014.
Disclosures: The study presenter reported having no financial conflicts.
CRT-D beneficial in mild HF with ejection fraction above 30%
WASHINGTON – Patients with mild heart failure symptoms, left bundle branch block, and a left ventricular ejection fraction of 31% to 44% who received cardiac resynchronization therapy with a built-in defibrillator experienced a significant reduction in all-cause mortality, compared with those randomized to an implantable cardioverter-defibrillator alone during 7 years of follow-up.
These results from a new MADIT-CRT (Multicenter Automatic Defibrillator Implantation Trial With Cardiac Resynchronization Therapy) long-term follow-up substudy “suggest that patients with a relatively preserved ejection fraction greater than 30% benefit from CRT-D [cardiac resynchronization therapy defibrillator] and could potentially be considered for this therapy,” said Katherine Vermilye, MD, at the annual meeting of the American College of Cardiology.
In a subsequent publication, the MADIT-CRT investigators reported that, with extension of follow-up to 7 years, CRT-D also provided a significant benefit in terms of all-cause mortality in addition to the reduced rate of heart failure events (N Engl J Med. 2014 May 1;370[18]:1694-701).
However, even though an LVEF of 30% or less was a requirement for participation in MADIT-CRT, it turned out that, when the initial screening echocardiograms were eventually analyzed in a central core laboratory, one-third of study participants actually had a baseline LVEF of 31% to 44%, with the majority of excessive values being in the 31%-35% range.
Dr. Vermilye, of the University of Rochester in New York, presented a post hoc analysis of long-term outcomes in the subgroup having a baseline LVEF greater than 30%. They totaled 450 of 1,224 MADIT-CRT participants with left bundle branch block. They were significantly older and more likely to be female than the 824 subjects with an LVEF of 30% or less. They also had a shorter QRS duration – an average of 160 ms, versus 165 ms in patients with an LVEF of 30% or lower – and a smaller baseline left ventricular end systolic volume of 151 mL, compared with 196 mL in patients with a lower LVEF.
In a multivariate Cox regression analysis adjusted for potential confounders, CRT-D in patients with a baseline LVEF greater than 30% was associated with a 54% reduction in the risk of all-cause mortality at 7 years of follow-up, compared with receipt of an ICD-only device and with a smaller yet significant 31% reduction in risk in those with an LVEF of 30% or less. Worsening heart failure events were reduced by 64% in patients with a baseline LVEF greater than 30% who received CRT-D, compared with ICD-only, and by 54% in those with a lower baseline LVEF.
The reduction in all-cause mortality seen with CRT-D was confined to patients who were high responders to CRT as defined echocardiographically by at least a 35% change in left ventricular end systolic volume 1 year post implantation. They had an 85% reduction in the risk of death during 7 years of follow-up with CRT-D if their baseline LVEF was greater than 30% and a 58% relative risk reduction if their LVEF was 30% or less.
In contrast, CRT-D brought a significantly reduced risk of heart failure events regardless of whether a patient was a low or high responder, although the magnitude of benefit was greater in the high responders. Among patients with a baseline LVEF greater than 30%, CRT-D low responders had a 52% reduction in risk of heart failure events, compared with ICD recipients, while CRT-D high responders had an 81% relative risk reduction. Similarly, in patients with a baseline LVEF of 30% or less, CRT-D low responders had 48% reduction in heart failure events and high responders had a 79% risk reduction, compared with the ICD-only group.
Because this is a post hoc analysis, these new MADIT-CRT findings require validation in future studies, Dr. Vermilye observed.
MADIT-CRT was supported by Boston Scientific. Dr.. Vermilye reported having no financial conflicts.
The authors demonstrate the benefit of cardiac resynchronization therapy in patients with a defibrillator. The reduction in mortality at 5 years was greater in high responders to CRT-D, although overall mortality was significantly reduced in all comers.
The authors demonstrate the benefit of cardiac resynchronization therapy in patients with a defibrillator. The reduction in mortality at 5 years was greater in high responders to CRT-D, although overall mortality was significantly reduced in all comers.
The authors demonstrate the benefit of cardiac resynchronization therapy in patients with a defibrillator. The reduction in mortality at 5 years was greater in high responders to CRT-D, although overall mortality was significantly reduced in all comers.
WASHINGTON – Patients with mild heart failure symptoms, left bundle branch block, and a left ventricular ejection fraction of 31% to 44% who received cardiac resynchronization therapy with a built-in defibrillator experienced a significant reduction in all-cause mortality, compared with those randomized to an implantable cardioverter-defibrillator alone during 7 years of follow-up.
These results from a new MADIT-CRT (Multicenter Automatic Defibrillator Implantation Trial With Cardiac Resynchronization Therapy) long-term follow-up substudy “suggest that patients with a relatively preserved ejection fraction greater than 30% benefit from CRT-D [cardiac resynchronization therapy defibrillator] and could potentially be considered for this therapy,” said Katherine Vermilye, MD, at the annual meeting of the American College of Cardiology.
In a subsequent publication, the MADIT-CRT investigators reported that, with extension of follow-up to 7 years, CRT-D also provided a significant benefit in terms of all-cause mortality in addition to the reduced rate of heart failure events (N Engl J Med. 2014 May 1;370[18]:1694-701).
However, even though an LVEF of 30% or less was a requirement for participation in MADIT-CRT, it turned out that, when the initial screening echocardiograms were eventually analyzed in a central core laboratory, one-third of study participants actually had a baseline LVEF of 31% to 44%, with the majority of excessive values being in the 31%-35% range.
Dr. Vermilye, of the University of Rochester in New York, presented a post hoc analysis of long-term outcomes in the subgroup having a baseline LVEF greater than 30%. They totaled 450 of 1,224 MADIT-CRT participants with left bundle branch block. They were significantly older and more likely to be female than the 824 subjects with an LVEF of 30% or less. They also had a shorter QRS duration – an average of 160 ms, versus 165 ms in patients with an LVEF of 30% or lower – and a smaller baseline left ventricular end systolic volume of 151 mL, compared with 196 mL in patients with a lower LVEF.
In a multivariate Cox regression analysis adjusted for potential confounders, CRT-D in patients with a baseline LVEF greater than 30% was associated with a 54% reduction in the risk of all-cause mortality at 7 years of follow-up, compared with receipt of an ICD-only device and with a smaller yet significant 31% reduction in risk in those with an LVEF of 30% or less. Worsening heart failure events were reduced by 64% in patients with a baseline LVEF greater than 30% who received CRT-D, compared with ICD-only, and by 54% in those with a lower baseline LVEF.
The reduction in all-cause mortality seen with CRT-D was confined to patients who were high responders to CRT as defined echocardiographically by at least a 35% change in left ventricular end systolic volume 1 year post implantation. They had an 85% reduction in the risk of death during 7 years of follow-up with CRT-D if their baseline LVEF was greater than 30% and a 58% relative risk reduction if their LVEF was 30% or less.
In contrast, CRT-D brought a significantly reduced risk of heart failure events regardless of whether a patient was a low or high responder, although the magnitude of benefit was greater in the high responders. Among patients with a baseline LVEF greater than 30%, CRT-D low responders had a 52% reduction in risk of heart failure events, compared with ICD recipients, while CRT-D high responders had an 81% relative risk reduction. Similarly, in patients with a baseline LVEF of 30% or less, CRT-D low responders had 48% reduction in heart failure events and high responders had a 79% risk reduction, compared with the ICD-only group.
Because this is a post hoc analysis, these new MADIT-CRT findings require validation in future studies, Dr. Vermilye observed.
MADIT-CRT was supported by Boston Scientific. Dr.. Vermilye reported having no financial conflicts.
WASHINGTON – Patients with mild heart failure symptoms, left bundle branch block, and a left ventricular ejection fraction of 31% to 44% who received cardiac resynchronization therapy with a built-in defibrillator experienced a significant reduction in all-cause mortality, compared with those randomized to an implantable cardioverter-defibrillator alone during 7 years of follow-up.
These results from a new MADIT-CRT (Multicenter Automatic Defibrillator Implantation Trial With Cardiac Resynchronization Therapy) long-term follow-up substudy “suggest that patients with a relatively preserved ejection fraction greater than 30% benefit from CRT-D [cardiac resynchronization therapy defibrillator] and could potentially be considered for this therapy,” said Katherine Vermilye, MD, at the annual meeting of the American College of Cardiology.
In a subsequent publication, the MADIT-CRT investigators reported that, with extension of follow-up to 7 years, CRT-D also provided a significant benefit in terms of all-cause mortality in addition to the reduced rate of heart failure events (N Engl J Med. 2014 May 1;370[18]:1694-701).
However, even though an LVEF of 30% or less was a requirement for participation in MADIT-CRT, it turned out that, when the initial screening echocardiograms were eventually analyzed in a central core laboratory, one-third of study participants actually had a baseline LVEF of 31% to 44%, with the majority of excessive values being in the 31%-35% range.
Dr. Vermilye, of the University of Rochester in New York, presented a post hoc analysis of long-term outcomes in the subgroup having a baseline LVEF greater than 30%. They totaled 450 of 1,224 MADIT-CRT participants with left bundle branch block. They were significantly older and more likely to be female than the 824 subjects with an LVEF of 30% or less. They also had a shorter QRS duration – an average of 160 ms, versus 165 ms in patients with an LVEF of 30% or lower – and a smaller baseline left ventricular end systolic volume of 151 mL, compared with 196 mL in patients with a lower LVEF.
In a multivariate Cox regression analysis adjusted for potential confounders, CRT-D in patients with a baseline LVEF greater than 30% was associated with a 54% reduction in the risk of all-cause mortality at 7 years of follow-up, compared with receipt of an ICD-only device and with a smaller yet significant 31% reduction in risk in those with an LVEF of 30% or less. Worsening heart failure events were reduced by 64% in patients with a baseline LVEF greater than 30% who received CRT-D, compared with ICD-only, and by 54% in those with a lower baseline LVEF.
The reduction in all-cause mortality seen with CRT-D was confined to patients who were high responders to CRT as defined echocardiographically by at least a 35% change in left ventricular end systolic volume 1 year post implantation. They had an 85% reduction in the risk of death during 7 years of follow-up with CRT-D if their baseline LVEF was greater than 30% and a 58% relative risk reduction if their LVEF was 30% or less.
In contrast, CRT-D brought a significantly reduced risk of heart failure events regardless of whether a patient was a low or high responder, although the magnitude of benefit was greater in the high responders. Among patients with a baseline LVEF greater than 30%, CRT-D low responders had a 52% reduction in risk of heart failure events, compared with ICD recipients, while CRT-D high responders had an 81% relative risk reduction. Similarly, in patients with a baseline LVEF of 30% or less, CRT-D low responders had 48% reduction in heart failure events and high responders had a 79% risk reduction, compared with the ICD-only group.
Because this is a post hoc analysis, these new MADIT-CRT findings require validation in future studies, Dr. Vermilye observed.
MADIT-CRT was supported by Boston Scientific. Dr.. Vermilye reported having no financial conflicts.
AT ACC 2017
Key clinical point:
Major finding: The risk of all-cause mortality was reduced by 54% with CRT-D as compared with an ICD alone in MADIT-CRT participants with a baseline LVEF greater than 30% and by 31% in those with an LVEF of 30% or lower.
Data source: An analysis of 7-year rates of all-cause mortality and worsening heart failure events in 1,224 MADIT-CRT participants with left bundle branch block, 450 of whom had a baseline LVEF greater than 30%.
Disclosures: The MADIT-CRT study was supported by Boston Scientific. The presenter reported having no financial conflicts.
It’s been a good year for heart failure research ... mostly
WASHINGTON – It’s been a “relatively positive” year for heart failure research and advances in patient care, Christopher M. O’Connor, MD, said at the annual meeting of the American College of Cardiology.
“Having been in this field for 30 years looking at clinical trials, generally for every 10 important trials done in a year, 1 has been positive and 9 have been negative; if we look at the past year, it’s more like 5 and 6. So, not a bad year for cardiomyopathy,” declared Dr. O’Connor, CEO and executive director of the Inova Heart and Vascular Institute in Falls Church, Va., and president-elect of the Heart Failure Society of America.
The good news
• Empagliflozin (Jardiance) earns FDA approval for reduction in risk of cardiovascular death in type 2 diabetes patients. “This is one of the most amazing stories in heart failure,” said Dr. O’Connor, who is also professor of medicine at Duke University in Durham, N.C.
The pivotal EMPA-REG OUTCOME study showed a highly significant 35% reduction in the secondary endpoint of risk of hospitalization for heart failure, as well the decrease in cardiovascular mortality which was the primary endpoint and proved persuasive to the FDA (N Engl J Med. 2015 Nov 26;373[22]:2117-28).
“It was a remarkable development. Because of this trial, there are now a number of ongoing phase III clinical trials looking at this class of drugs in heart failure patients with and without diabetes, which makes this a very important research movement. We are now looking deeper at phenotypes and trying to get more specific with these drug therapies,” he said.
• A new and improved LVAD. This fully magnetically levitated centrifugal-flow pump type of left ventricular assist device for advanced heart failure showed superior event-free survival, compared with a commercially available axial continuous-flow pump LVAD in the randomized MOMENTUM-3 trial (N Engl J Med. 2017 Feb 2;376[5]:440-50).
The novel pump was designed to overcome a significant problem with axial continuous-flow LVADs: a proclivity for pump thrombosis. The magnetically levitated centrifugal-flow pump proved a smashing success in this regard, with zero cases of pump thrombosis occurring during the 6-month study.
“This may be the first time in the history of heart failure research that the engineers have beaten the biologists in important clinical outcomes,” the cardiologist quipped.
• Omecamtiv mecarbil successfully addresses impaired contractility in heart failure with reduced ejection fraction (HFrEF). This drug, a selective cardiac myosin activator, resulted in increased duration of systole and improved stroke volume accompanied by reductions in heart rate, left ventricular end-diastolic and -systolic dimensions, and NT-proBNP in the 87-site, 13-country, phase II COSMIC-HF study (Lancet. 2016 Dec 10;388[10062]:2895-903).
“This is probably the most novel new drug mechanism out there in clinical trials,” according to Dr. O’Connor.
On the basis of the highly encouraging results for the surrogate endpoints assessed in COSMIC-HF, a large phase III clinical trial known as GALACTIC is underway.
• Palliative care gets a welcome boost. Dr. O’Connor was a coinvestigator in PAL-HF, a single-center study presented at the 2016 annual meeting of the Heart Failure Society of America.
“This is a very important trial of palliative care in advanced heart failure. We probably don’t have as much evidence in this space as we should,” he observed. “This was a multidisciplinary intervention in which we gave the patients a medical tool kit to alleviate pain, dyspnea, and discomfort. The tool kit included benzodiazepines, sleep medications, sublingual nitroglycerin, and morphinelike products, all very carefully monitored by staff coordinators.”
The primary outcome was change in two validated heart failure quality of life measures. Both instruments documented significant improvement compared with usual care.
“There was no decrease in mortality, which wasn’t a goal in this advanced heart failure population, and no reduction in heart failure hospitalizations, but there were significant reductions in depression and anxiety,” Dr. O’Connor said.
• Vericiguat. This oral soluble cyclic guanylate cyclase stimulator missed its primary endpoint in the phase II dose-escalation SOCRATES-REDUCED trial in patients with HFrEF (JAMA. 2015 Dec 1;314[21]:2251-62), but showed an impressive improvement in quality of life. It is now the subject of the ongoing, randomized, phase III VICTORIA trial involving a planned 4,000 patients with HFrEF with the composite primary endpoint of cardiovascular death or heart failure hospitalization.
The phase II SOCRATES-PRESERVED trial also missed its primary endpoint but showed a clinically meaningful improvement in quality of life in patients with heart failure with preserved ejection fraction (HFpEF) (Eur Heart J. 2017 Mar 22. doi: 10.1093/eurheartj/ehw593). Discussions are ongoing as to whether the next step should be a confirmatory phase II study or a move straight to phase III.
The bad news
• NSAIDs linked to increased risk of heart failure. European investigators analyzed five population-based databases totaling more than 8.3 million individuals and determined that current use of any of more than two dozen NSAIDs was associated with significantly increased risk of hospital admission for heart failure. The risk appeared to be dose dependent and varied between individual agents, ranging from a 16% increased risk with naproxen to an 83% increase with ketorolac (Toradol) (BMJ. 2016 Sep 28. doi: 10.1136/bmj.4857).
• Therapeutic natriuretic peptides hit bottom. The negative results for the investigational agent ularitide in patients with acute decompensated heart failure in the large phase III TRUE-AHF trial presented at the 2016 meeting of the American Heart Association, following upon an earlier negative study of the related drug nesiritide (Natrecor) in more than 7,100 acute heart failure patients (N Engl J Med. 2011 Jul 7; 365:32-43), probably spells the end of the line for this strategy of boosting outcomes in acute heart failure, according to Dr. O’Connor.
Moreover, Novartis has announced that the phase III RELAX-AHF-2 trial of serelaxin in 6,600 patients with acute heart failure failed to meet its primary endpoints of reduced cardiovascular deaths or reduced worsening of heart failure. The trial will be formally presented later this year.
“Ularitide seemed to show an early improvement in heart failure events that was not sustained in-hospital, and there was absolutely no difference in mortality. The drug probably acts like a pharmacologic tourniquet, in my view. So I think this field of therapeutic natriuretic peptides is probably closed,” he said.
• ICDs don’t reduce mortality in patients with nonischemic heart failure. This was the conclusion reached in the DANISH trial, in which more than 1,100 patients with symptomatic systolic heart failure were randomized to an ICD or usual care (N Engl J Med. 2016 Sep 29;375[13]:1221-30).
“This study really shook up the field, raising the question, ‘Are we using defibrillators too frequently in this population?’ It has stimulated a lot of discussion, including within the guidelines committee,” according to Dr. O’Connor.
• Tolvaptan nixed for acute decompensated heart failure. The TACTICS-HF trial studied the use of tolvaptan (Samsca), an oral vasopressin-2 receptor antagonist, to reduce dyspnea in patients hospitalized with acute decompensated heart failure. Dr. O’Connor was a coinvestigator in the study, which showed that tolvaptan was no better than placebo at 8 and 24 hours (J Am Coll Cardiol. 2017 Mar 21;69[11]:1399-406).
“For now, the routine use of vasopressin antagonists in acute heart failure is not to be encouraged, although there may still be subsets where it’s worth trying – certainly in severe hyponatremia,” the cardiologist said.
• GUIDE-IT gets lost. This was a roughly 1,000-patient randomized trial of a treatment strategy aimed at improving clinical outcomes by aggressively titrating evidence-based heart failure therapies in order to suppress natriuretic peptide biomarkers. GUIDE-IT was stopped early by the data safety monitoring board due to a lack of discernible difference in outcomes, compared with usual care. Dr. O’Connor, a coinvestigator, termed the soon-to-be-published study “a disappointment.”
Sleep apnea studies show silver lining
Sleep apnea is common in patients with heart failure and is associated with worse clinical heart failure outcomes. But in the large, randomized SERVE-HF trial, investigators showed that treatment of central sleep apnea with adaptive servo-ventilation in patients with HFrEF unexpectedly increased mortality, compared with optimal medical therapy (N Engl J Med. 2015 Sep 17;373:1095-105). In a more recent secondary analysis, however, the SERVE-HF investigators found that the increased risk for cardiovascular death associated with adaptive servo-ventilation was actually restricted to patients with a very poor left ventricular ejection fraction of 30% or less, and there was a signal of possible benefit in patients in the top tier of LVEF, at 36%-45% (Lancet Respir Med. 2016 Nov; 4[11]:873-81).
This observation dovetails nicely with the findings of the CAT-HF trial presented by Dr. O’Connor at the 2016 World Congress on Heart Failure. In this phase II study, 215 patients with acute decompensated heart failure and either obstructive or central sleep apnea were randomized to optimal medical therapy alone or in combination with adaptive servo-ventilation. There was no overall difference in outcome between the two groups; however, in the subgroup of patients with HFpEF, the risk of the primary composite endpoint was reduced by 62% with adaptive servo-ventilation.
As a result of these intriguing findings from SERVE-HF and CAT-HF, a registry and/or randomized clinical trial of adaptive servo-ventilation in patients with HFpEF is now being considered under NIH sponsorship, according to Dr. O’Connor.
He reported having no financial conflicts.
WASHINGTON – It’s been a “relatively positive” year for heart failure research and advances in patient care, Christopher M. O’Connor, MD, said at the annual meeting of the American College of Cardiology.
“Having been in this field for 30 years looking at clinical trials, generally for every 10 important trials done in a year, 1 has been positive and 9 have been negative; if we look at the past year, it’s more like 5 and 6. So, not a bad year for cardiomyopathy,” declared Dr. O’Connor, CEO and executive director of the Inova Heart and Vascular Institute in Falls Church, Va., and president-elect of the Heart Failure Society of America.
The good news
• Empagliflozin (Jardiance) earns FDA approval for reduction in risk of cardiovascular death in type 2 diabetes patients. “This is one of the most amazing stories in heart failure,” said Dr. O’Connor, who is also professor of medicine at Duke University in Durham, N.C.
The pivotal EMPA-REG OUTCOME study showed a highly significant 35% reduction in the secondary endpoint of risk of hospitalization for heart failure, as well the decrease in cardiovascular mortality which was the primary endpoint and proved persuasive to the FDA (N Engl J Med. 2015 Nov 26;373[22]:2117-28).
“It was a remarkable development. Because of this trial, there are now a number of ongoing phase III clinical trials looking at this class of drugs in heart failure patients with and without diabetes, which makes this a very important research movement. We are now looking deeper at phenotypes and trying to get more specific with these drug therapies,” he said.
• A new and improved LVAD. This fully magnetically levitated centrifugal-flow pump type of left ventricular assist device for advanced heart failure showed superior event-free survival, compared with a commercially available axial continuous-flow pump LVAD in the randomized MOMENTUM-3 trial (N Engl J Med. 2017 Feb 2;376[5]:440-50).
The novel pump was designed to overcome a significant problem with axial continuous-flow LVADs: a proclivity for pump thrombosis. The magnetically levitated centrifugal-flow pump proved a smashing success in this regard, with zero cases of pump thrombosis occurring during the 6-month study.
“This may be the first time in the history of heart failure research that the engineers have beaten the biologists in important clinical outcomes,” the cardiologist quipped.
• Omecamtiv mecarbil successfully addresses impaired contractility in heart failure with reduced ejection fraction (HFrEF). This drug, a selective cardiac myosin activator, resulted in increased duration of systole and improved stroke volume accompanied by reductions in heart rate, left ventricular end-diastolic and -systolic dimensions, and NT-proBNP in the 87-site, 13-country, phase II COSMIC-HF study (Lancet. 2016 Dec 10;388[10062]:2895-903).
“This is probably the most novel new drug mechanism out there in clinical trials,” according to Dr. O’Connor.
On the basis of the highly encouraging results for the surrogate endpoints assessed in COSMIC-HF, a large phase III clinical trial known as GALACTIC is underway.
• Palliative care gets a welcome boost. Dr. O’Connor was a coinvestigator in PAL-HF, a single-center study presented at the 2016 annual meeting of the Heart Failure Society of America.
“This is a very important trial of palliative care in advanced heart failure. We probably don’t have as much evidence in this space as we should,” he observed. “This was a multidisciplinary intervention in which we gave the patients a medical tool kit to alleviate pain, dyspnea, and discomfort. The tool kit included benzodiazepines, sleep medications, sublingual nitroglycerin, and morphinelike products, all very carefully monitored by staff coordinators.”
The primary outcome was change in two validated heart failure quality of life measures. Both instruments documented significant improvement compared with usual care.
“There was no decrease in mortality, which wasn’t a goal in this advanced heart failure population, and no reduction in heart failure hospitalizations, but there were significant reductions in depression and anxiety,” Dr. O’Connor said.
• Vericiguat. This oral soluble cyclic guanylate cyclase stimulator missed its primary endpoint in the phase II dose-escalation SOCRATES-REDUCED trial in patients with HFrEF (JAMA. 2015 Dec 1;314[21]:2251-62), but showed an impressive improvement in quality of life. It is now the subject of the ongoing, randomized, phase III VICTORIA trial involving a planned 4,000 patients with HFrEF with the composite primary endpoint of cardiovascular death or heart failure hospitalization.
The phase II SOCRATES-PRESERVED trial also missed its primary endpoint but showed a clinically meaningful improvement in quality of life in patients with heart failure with preserved ejection fraction (HFpEF) (Eur Heart J. 2017 Mar 22. doi: 10.1093/eurheartj/ehw593). Discussions are ongoing as to whether the next step should be a confirmatory phase II study or a move straight to phase III.
The bad news
• NSAIDs linked to increased risk of heart failure. European investigators analyzed five population-based databases totaling more than 8.3 million individuals and determined that current use of any of more than two dozen NSAIDs was associated with significantly increased risk of hospital admission for heart failure. The risk appeared to be dose dependent and varied between individual agents, ranging from a 16% increased risk with naproxen to an 83% increase with ketorolac (Toradol) (BMJ. 2016 Sep 28. doi: 10.1136/bmj.4857).
• Therapeutic natriuretic peptides hit bottom. The negative results for the investigational agent ularitide in patients with acute decompensated heart failure in the large phase III TRUE-AHF trial presented at the 2016 meeting of the American Heart Association, following upon an earlier negative study of the related drug nesiritide (Natrecor) in more than 7,100 acute heart failure patients (N Engl J Med. 2011 Jul 7; 365:32-43), probably spells the end of the line for this strategy of boosting outcomes in acute heart failure, according to Dr. O’Connor.
Moreover, Novartis has announced that the phase III RELAX-AHF-2 trial of serelaxin in 6,600 patients with acute heart failure failed to meet its primary endpoints of reduced cardiovascular deaths or reduced worsening of heart failure. The trial will be formally presented later this year.
“Ularitide seemed to show an early improvement in heart failure events that was not sustained in-hospital, and there was absolutely no difference in mortality. The drug probably acts like a pharmacologic tourniquet, in my view. So I think this field of therapeutic natriuretic peptides is probably closed,” he said.
• ICDs don’t reduce mortality in patients with nonischemic heart failure. This was the conclusion reached in the DANISH trial, in which more than 1,100 patients with symptomatic systolic heart failure were randomized to an ICD or usual care (N Engl J Med. 2016 Sep 29;375[13]:1221-30).
“This study really shook up the field, raising the question, ‘Are we using defibrillators too frequently in this population?’ It has stimulated a lot of discussion, including within the guidelines committee,” according to Dr. O’Connor.
• Tolvaptan nixed for acute decompensated heart failure. The TACTICS-HF trial studied the use of tolvaptan (Samsca), an oral vasopressin-2 receptor antagonist, to reduce dyspnea in patients hospitalized with acute decompensated heart failure. Dr. O’Connor was a coinvestigator in the study, which showed that tolvaptan was no better than placebo at 8 and 24 hours (J Am Coll Cardiol. 2017 Mar 21;69[11]:1399-406).
“For now, the routine use of vasopressin antagonists in acute heart failure is not to be encouraged, although there may still be subsets where it’s worth trying – certainly in severe hyponatremia,” the cardiologist said.
• GUIDE-IT gets lost. This was a roughly 1,000-patient randomized trial of a treatment strategy aimed at improving clinical outcomes by aggressively titrating evidence-based heart failure therapies in order to suppress natriuretic peptide biomarkers. GUIDE-IT was stopped early by the data safety monitoring board due to a lack of discernible difference in outcomes, compared with usual care. Dr. O’Connor, a coinvestigator, termed the soon-to-be-published study “a disappointment.”
Sleep apnea studies show silver lining
Sleep apnea is common in patients with heart failure and is associated with worse clinical heart failure outcomes. But in the large, randomized SERVE-HF trial, investigators showed that treatment of central sleep apnea with adaptive servo-ventilation in patients with HFrEF unexpectedly increased mortality, compared with optimal medical therapy (N Engl J Med. 2015 Sep 17;373:1095-105). In a more recent secondary analysis, however, the SERVE-HF investigators found that the increased risk for cardiovascular death associated with adaptive servo-ventilation was actually restricted to patients with a very poor left ventricular ejection fraction of 30% or less, and there was a signal of possible benefit in patients in the top tier of LVEF, at 36%-45% (Lancet Respir Med. 2016 Nov; 4[11]:873-81).
This observation dovetails nicely with the findings of the CAT-HF trial presented by Dr. O’Connor at the 2016 World Congress on Heart Failure. In this phase II study, 215 patients with acute decompensated heart failure and either obstructive or central sleep apnea were randomized to optimal medical therapy alone or in combination with adaptive servo-ventilation. There was no overall difference in outcome between the two groups; however, in the subgroup of patients with HFpEF, the risk of the primary composite endpoint was reduced by 62% with adaptive servo-ventilation.
As a result of these intriguing findings from SERVE-HF and CAT-HF, a registry and/or randomized clinical trial of adaptive servo-ventilation in patients with HFpEF is now being considered under NIH sponsorship, according to Dr. O’Connor.
He reported having no financial conflicts.
WASHINGTON – It’s been a “relatively positive” year for heart failure research and advances in patient care, Christopher M. O’Connor, MD, said at the annual meeting of the American College of Cardiology.
“Having been in this field for 30 years looking at clinical trials, generally for every 10 important trials done in a year, 1 has been positive and 9 have been negative; if we look at the past year, it’s more like 5 and 6. So, not a bad year for cardiomyopathy,” declared Dr. O’Connor, CEO and executive director of the Inova Heart and Vascular Institute in Falls Church, Va., and president-elect of the Heart Failure Society of America.
The good news
• Empagliflozin (Jardiance) earns FDA approval for reduction in risk of cardiovascular death in type 2 diabetes patients. “This is one of the most amazing stories in heart failure,” said Dr. O’Connor, who is also professor of medicine at Duke University in Durham, N.C.
The pivotal EMPA-REG OUTCOME study showed a highly significant 35% reduction in the secondary endpoint of risk of hospitalization for heart failure, as well the decrease in cardiovascular mortality which was the primary endpoint and proved persuasive to the FDA (N Engl J Med. 2015 Nov 26;373[22]:2117-28).
“It was a remarkable development. Because of this trial, there are now a number of ongoing phase III clinical trials looking at this class of drugs in heart failure patients with and without diabetes, which makes this a very important research movement. We are now looking deeper at phenotypes and trying to get more specific with these drug therapies,” he said.
• A new and improved LVAD. This fully magnetically levitated centrifugal-flow pump type of left ventricular assist device for advanced heart failure showed superior event-free survival, compared with a commercially available axial continuous-flow pump LVAD in the randomized MOMENTUM-3 trial (N Engl J Med. 2017 Feb 2;376[5]:440-50).
The novel pump was designed to overcome a significant problem with axial continuous-flow LVADs: a proclivity for pump thrombosis. The magnetically levitated centrifugal-flow pump proved a smashing success in this regard, with zero cases of pump thrombosis occurring during the 6-month study.
“This may be the first time in the history of heart failure research that the engineers have beaten the biologists in important clinical outcomes,” the cardiologist quipped.
• Omecamtiv mecarbil successfully addresses impaired contractility in heart failure with reduced ejection fraction (HFrEF). This drug, a selective cardiac myosin activator, resulted in increased duration of systole and improved stroke volume accompanied by reductions in heart rate, left ventricular end-diastolic and -systolic dimensions, and NT-proBNP in the 87-site, 13-country, phase II COSMIC-HF study (Lancet. 2016 Dec 10;388[10062]:2895-903).
“This is probably the most novel new drug mechanism out there in clinical trials,” according to Dr. O’Connor.
On the basis of the highly encouraging results for the surrogate endpoints assessed in COSMIC-HF, a large phase III clinical trial known as GALACTIC is underway.
• Palliative care gets a welcome boost. Dr. O’Connor was a coinvestigator in PAL-HF, a single-center study presented at the 2016 annual meeting of the Heart Failure Society of America.
“This is a very important trial of palliative care in advanced heart failure. We probably don’t have as much evidence in this space as we should,” he observed. “This was a multidisciplinary intervention in which we gave the patients a medical tool kit to alleviate pain, dyspnea, and discomfort. The tool kit included benzodiazepines, sleep medications, sublingual nitroglycerin, and morphinelike products, all very carefully monitored by staff coordinators.”
The primary outcome was change in two validated heart failure quality of life measures. Both instruments documented significant improvement compared with usual care.
“There was no decrease in mortality, which wasn’t a goal in this advanced heart failure population, and no reduction in heart failure hospitalizations, but there were significant reductions in depression and anxiety,” Dr. O’Connor said.
• Vericiguat. This oral soluble cyclic guanylate cyclase stimulator missed its primary endpoint in the phase II dose-escalation SOCRATES-REDUCED trial in patients with HFrEF (JAMA. 2015 Dec 1;314[21]:2251-62), but showed an impressive improvement in quality of life. It is now the subject of the ongoing, randomized, phase III VICTORIA trial involving a planned 4,000 patients with HFrEF with the composite primary endpoint of cardiovascular death or heart failure hospitalization.
The phase II SOCRATES-PRESERVED trial also missed its primary endpoint but showed a clinically meaningful improvement in quality of life in patients with heart failure with preserved ejection fraction (HFpEF) (Eur Heart J. 2017 Mar 22. doi: 10.1093/eurheartj/ehw593). Discussions are ongoing as to whether the next step should be a confirmatory phase II study or a move straight to phase III.
The bad news
• NSAIDs linked to increased risk of heart failure. European investigators analyzed five population-based databases totaling more than 8.3 million individuals and determined that current use of any of more than two dozen NSAIDs was associated with significantly increased risk of hospital admission for heart failure. The risk appeared to be dose dependent and varied between individual agents, ranging from a 16% increased risk with naproxen to an 83% increase with ketorolac (Toradol) (BMJ. 2016 Sep 28. doi: 10.1136/bmj.4857).
• Therapeutic natriuretic peptides hit bottom. The negative results for the investigational agent ularitide in patients with acute decompensated heart failure in the large phase III TRUE-AHF trial presented at the 2016 meeting of the American Heart Association, following upon an earlier negative study of the related drug nesiritide (Natrecor) in more than 7,100 acute heart failure patients (N Engl J Med. 2011 Jul 7; 365:32-43), probably spells the end of the line for this strategy of boosting outcomes in acute heart failure, according to Dr. O’Connor.
Moreover, Novartis has announced that the phase III RELAX-AHF-2 trial of serelaxin in 6,600 patients with acute heart failure failed to meet its primary endpoints of reduced cardiovascular deaths or reduced worsening of heart failure. The trial will be formally presented later this year.
“Ularitide seemed to show an early improvement in heart failure events that was not sustained in-hospital, and there was absolutely no difference in mortality. The drug probably acts like a pharmacologic tourniquet, in my view. So I think this field of therapeutic natriuretic peptides is probably closed,” he said.
• ICDs don’t reduce mortality in patients with nonischemic heart failure. This was the conclusion reached in the DANISH trial, in which more than 1,100 patients with symptomatic systolic heart failure were randomized to an ICD or usual care (N Engl J Med. 2016 Sep 29;375[13]:1221-30).
“This study really shook up the field, raising the question, ‘Are we using defibrillators too frequently in this population?’ It has stimulated a lot of discussion, including within the guidelines committee,” according to Dr. O’Connor.
• Tolvaptan nixed for acute decompensated heart failure. The TACTICS-HF trial studied the use of tolvaptan (Samsca), an oral vasopressin-2 receptor antagonist, to reduce dyspnea in patients hospitalized with acute decompensated heart failure. Dr. O’Connor was a coinvestigator in the study, which showed that tolvaptan was no better than placebo at 8 and 24 hours (J Am Coll Cardiol. 2017 Mar 21;69[11]:1399-406).
“For now, the routine use of vasopressin antagonists in acute heart failure is not to be encouraged, although there may still be subsets where it’s worth trying – certainly in severe hyponatremia,” the cardiologist said.
• GUIDE-IT gets lost. This was a roughly 1,000-patient randomized trial of a treatment strategy aimed at improving clinical outcomes by aggressively titrating evidence-based heart failure therapies in order to suppress natriuretic peptide biomarkers. GUIDE-IT was stopped early by the data safety monitoring board due to a lack of discernible difference in outcomes, compared with usual care. Dr. O’Connor, a coinvestigator, termed the soon-to-be-published study “a disappointment.”
Sleep apnea studies show silver lining
Sleep apnea is common in patients with heart failure and is associated with worse clinical heart failure outcomes. But in the large, randomized SERVE-HF trial, investigators showed that treatment of central sleep apnea with adaptive servo-ventilation in patients with HFrEF unexpectedly increased mortality, compared with optimal medical therapy (N Engl J Med. 2015 Sep 17;373:1095-105). In a more recent secondary analysis, however, the SERVE-HF investigators found that the increased risk for cardiovascular death associated with adaptive servo-ventilation was actually restricted to patients with a very poor left ventricular ejection fraction of 30% or less, and there was a signal of possible benefit in patients in the top tier of LVEF, at 36%-45% (Lancet Respir Med. 2016 Nov; 4[11]:873-81).
This observation dovetails nicely with the findings of the CAT-HF trial presented by Dr. O’Connor at the 2016 World Congress on Heart Failure. In this phase II study, 215 patients with acute decompensated heart failure and either obstructive or central sleep apnea were randomized to optimal medical therapy alone or in combination with adaptive servo-ventilation. There was no overall difference in outcome between the two groups; however, in the subgroup of patients with HFpEF, the risk of the primary composite endpoint was reduced by 62% with adaptive servo-ventilation.
As a result of these intriguing findings from SERVE-HF and CAT-HF, a registry and/or randomized clinical trial of adaptive servo-ventilation in patients with HFpEF is now being considered under NIH sponsorship, according to Dr. O’Connor.
He reported having no financial conflicts.
EXPERT ANALYSIS FROM ACC 17
PAP sensor may cut real-world heart failure hospitalization
Implantation of a pulmonary artery pressure sensor to guide care in chronic heart failure was associated with a significant 45% reduction in HF hospitalization and its attendant substantial costs in a real-world patient population, Akshay S. Desai, MD, said at the annual meeting of the American College of Cardiology.
The PAP sensor is used to monitor pulmonary artery filling pressure, which rises in many HF patients during the weeks preceding an HF exacerbation. This early detection of progressing congestion allows clinicians to intervene earlier and head off hospitalization for the exacerbation.
Their intention was to determine whether the positive results of the CHAMPION clinical trial, which prompted FDA approval of the device as a means to reduce HF-associated hospitalizations, could be replicated in a real-world population, said Dr. Desai of Brigham and Women’s Hospital, Boston.
The results of their study were presented March 19 at the annual meeting of the American College of Cardiology and simultaneously published online in the Journal of the American College of Cardiology (2017 Mar 19. doi: 10.1016/j.jacc.2017.03.009).
The mean age of the study cohort was 71 years, and 40% of the participants were at least 75 years of age. Women composed 40% of the cohort. There was a high burden of comorbid illness, including diabetes, hypertension, and chronic obstructive pulmonary disease. This represents a broader sample than was enrolled in the CHAMPION trial, he noted.
There were 1,020 HF hospitalizations before implantation and 381 afterward. A total of 59% of patients had at least one HF hospitalization before the PAP implantation, compared with 22% afterward. The median number of HF hospitalizations was 0.92 per patient before implantation and 0.37 per patient afterward.
Further analysis showed that the cumulative rate of HF hospitalization was 45% lower during the 6 months after implantation than during the 6 months preceding it (hazard ratio, 0.55). This finding remained robust across several subgroups of patients and in several sensitivity analyses.
These reductions were associated with a corresponding decline in costs related to HF care, which dropped by $7,433 per patient.
In addition to HF-related hospitalizations, all-cause hospitalizations also declined by roughly 30% after implantation of a PAP sensor (HR, 0.69).
These findings suggest that the reduction in hospitalizations, along with attendant reductions in the costs of care, may be achievable in real-world practice. The 45% drop in HF hospitalizations in this study “compares favorably with the 28% reduction seen with PAP-guided therapy over the same time period in the randomized CHAMPION study that supported the initial FDA approval,” Dr. Desai said.
Moreover, a subgroup of 480 patients had data for 12 months preceding and 12 months following implantation. Analysis of those data showed that the benefits of PAP monitoring to guide HF care “were consistent over longer-term follow-up, with a 34% reduction in HF hospitalizations sustained at 12 months,” he added.
The study had several limitations. It excluded Medicare Part D data, so medication changes related to implantation could not be examined and may have exerted substantial influence on study outcomes.
It also didn’t include the actual PAP-sensor data, “which makes it challenging to confirm that physicians intervened to treat elevated PAPs” and that that intervention is the reason for the study outcomes.
“We were unable to definitively ascertain whether reduced HF hospitalizations are related to undertreatment in the preimplant period or improved treatment in the postimplant period,” Dr. Desai said.
The study was sponsored by Abbott, maker of the CardioMEMS PAP sensor. Dr. Desai and his associates reported ties to Abbott and St. Jude Medical.
Real-world evidence about the PAP sensor is particularly important, because the FDA approved the device amid considerable controversy over the CHAMPION trial and its sponsor. Employees of the sponsor were considered to have contaminated the initial data, and the FDA initially rejected the device. Substantial uncertainty still persists concerning the sensor’s effectiveness in reducing HF hospitalizations.
In addition, the percentage of HF patients who have received the device is extremely small, given that the study and the highly selected patient sample make both causal inferences and generalizability of the findings difficult.
The net effect of these important limitations is that the study by Desai et al. lacks the strength to change prior assumptions about the PAP sensor’s benefits in any direction. Unfortunately, this study doesn’t have the evidentiary robustness to inform clinical decisions.
Harlan M. Krumholz, MD, and Sanket S. Dhruva, MD, are both in the Robert Wood Johnson Foundation Clinical Scholars Program and at the Yale School of Medicine and Yale School of Public Health in New Haven, Conn. Dr. Krumholz reported ties to Johnson & Johnson and Medtronic; Dr. Dhruva reported having no relevant financial disclosures. They made these remarks in an editorial accompanying the study (J Am Coll Cardiol. 2017 Mar 19. doi:10.1016/j.jacc.2017.03.019).
Real-world evidence about the PAP sensor is particularly important, because the FDA approved the device amid considerable controversy over the CHAMPION trial and its sponsor. Employees of the sponsor were considered to have contaminated the initial data, and the FDA initially rejected the device. Substantial uncertainty still persists concerning the sensor’s effectiveness in reducing HF hospitalizations.
In addition, the percentage of HF patients who have received the device is extremely small, given that the study and the highly selected patient sample make both causal inferences and generalizability of the findings difficult.
The net effect of these important limitations is that the study by Desai et al. lacks the strength to change prior assumptions about the PAP sensor’s benefits in any direction. Unfortunately, this study doesn’t have the evidentiary robustness to inform clinical decisions.
Harlan M. Krumholz, MD, and Sanket S. Dhruva, MD, are both in the Robert Wood Johnson Foundation Clinical Scholars Program and at the Yale School of Medicine and Yale School of Public Health in New Haven, Conn. Dr. Krumholz reported ties to Johnson & Johnson and Medtronic; Dr. Dhruva reported having no relevant financial disclosures. They made these remarks in an editorial accompanying the study (J Am Coll Cardiol. 2017 Mar 19. doi:10.1016/j.jacc.2017.03.019).
Real-world evidence about the PAP sensor is particularly important, because the FDA approved the device amid considerable controversy over the CHAMPION trial and its sponsor. Employees of the sponsor were considered to have contaminated the initial data, and the FDA initially rejected the device. Substantial uncertainty still persists concerning the sensor’s effectiveness in reducing HF hospitalizations.
In addition, the percentage of HF patients who have received the device is extremely small, given that the study and the highly selected patient sample make both causal inferences and generalizability of the findings difficult.
The net effect of these important limitations is that the study by Desai et al. lacks the strength to change prior assumptions about the PAP sensor’s benefits in any direction. Unfortunately, this study doesn’t have the evidentiary robustness to inform clinical decisions.
Harlan M. Krumholz, MD, and Sanket S. Dhruva, MD, are both in the Robert Wood Johnson Foundation Clinical Scholars Program and at the Yale School of Medicine and Yale School of Public Health in New Haven, Conn. Dr. Krumholz reported ties to Johnson & Johnson and Medtronic; Dr. Dhruva reported having no relevant financial disclosures. They made these remarks in an editorial accompanying the study (J Am Coll Cardiol. 2017 Mar 19. doi:10.1016/j.jacc.2017.03.019).
Implantation of a pulmonary artery pressure sensor to guide care in chronic heart failure was associated with a significant 45% reduction in HF hospitalization and its attendant substantial costs in a real-world patient population, Akshay S. Desai, MD, said at the annual meeting of the American College of Cardiology.
The PAP sensor is used to monitor pulmonary artery filling pressure, which rises in many HF patients during the weeks preceding an HF exacerbation. This early detection of progressing congestion allows clinicians to intervene earlier and head off hospitalization for the exacerbation.
Their intention was to determine whether the positive results of the CHAMPION clinical trial, which prompted FDA approval of the device as a means to reduce HF-associated hospitalizations, could be replicated in a real-world population, said Dr. Desai of Brigham and Women’s Hospital, Boston.
The results of their study were presented March 19 at the annual meeting of the American College of Cardiology and simultaneously published online in the Journal of the American College of Cardiology (2017 Mar 19. doi: 10.1016/j.jacc.2017.03.009).
The mean age of the study cohort was 71 years, and 40% of the participants were at least 75 years of age. Women composed 40% of the cohort. There was a high burden of comorbid illness, including diabetes, hypertension, and chronic obstructive pulmonary disease. This represents a broader sample than was enrolled in the CHAMPION trial, he noted.
There were 1,020 HF hospitalizations before implantation and 381 afterward. A total of 59% of patients had at least one HF hospitalization before the PAP implantation, compared with 22% afterward. The median number of HF hospitalizations was 0.92 per patient before implantation and 0.37 per patient afterward.
Further analysis showed that the cumulative rate of HF hospitalization was 45% lower during the 6 months after implantation than during the 6 months preceding it (hazard ratio, 0.55). This finding remained robust across several subgroups of patients and in several sensitivity analyses.
These reductions were associated with a corresponding decline in costs related to HF care, which dropped by $7,433 per patient.
In addition to HF-related hospitalizations, all-cause hospitalizations also declined by roughly 30% after implantation of a PAP sensor (HR, 0.69).
These findings suggest that the reduction in hospitalizations, along with attendant reductions in the costs of care, may be achievable in real-world practice. The 45% drop in HF hospitalizations in this study “compares favorably with the 28% reduction seen with PAP-guided therapy over the same time period in the randomized CHAMPION study that supported the initial FDA approval,” Dr. Desai said.
Moreover, a subgroup of 480 patients had data for 12 months preceding and 12 months following implantation. Analysis of those data showed that the benefits of PAP monitoring to guide HF care “were consistent over longer-term follow-up, with a 34% reduction in HF hospitalizations sustained at 12 months,” he added.
The study had several limitations. It excluded Medicare Part D data, so medication changes related to implantation could not be examined and may have exerted substantial influence on study outcomes.
It also didn’t include the actual PAP-sensor data, “which makes it challenging to confirm that physicians intervened to treat elevated PAPs” and that that intervention is the reason for the study outcomes.
“We were unable to definitively ascertain whether reduced HF hospitalizations are related to undertreatment in the preimplant period or improved treatment in the postimplant period,” Dr. Desai said.
The study was sponsored by Abbott, maker of the CardioMEMS PAP sensor. Dr. Desai and his associates reported ties to Abbott and St. Jude Medical.
Implantation of a pulmonary artery pressure sensor to guide care in chronic heart failure was associated with a significant 45% reduction in HF hospitalization and its attendant substantial costs in a real-world patient population, Akshay S. Desai, MD, said at the annual meeting of the American College of Cardiology.
The PAP sensor is used to monitor pulmonary artery filling pressure, which rises in many HF patients during the weeks preceding an HF exacerbation. This early detection of progressing congestion allows clinicians to intervene earlier and head off hospitalization for the exacerbation.
Their intention was to determine whether the positive results of the CHAMPION clinical trial, which prompted FDA approval of the device as a means to reduce HF-associated hospitalizations, could be replicated in a real-world population, said Dr. Desai of Brigham and Women’s Hospital, Boston.
The results of their study were presented March 19 at the annual meeting of the American College of Cardiology and simultaneously published online in the Journal of the American College of Cardiology (2017 Mar 19. doi: 10.1016/j.jacc.2017.03.009).
The mean age of the study cohort was 71 years, and 40% of the participants were at least 75 years of age. Women composed 40% of the cohort. There was a high burden of comorbid illness, including diabetes, hypertension, and chronic obstructive pulmonary disease. This represents a broader sample than was enrolled in the CHAMPION trial, he noted.
There were 1,020 HF hospitalizations before implantation and 381 afterward. A total of 59% of patients had at least one HF hospitalization before the PAP implantation, compared with 22% afterward. The median number of HF hospitalizations was 0.92 per patient before implantation and 0.37 per patient afterward.
Further analysis showed that the cumulative rate of HF hospitalization was 45% lower during the 6 months after implantation than during the 6 months preceding it (hazard ratio, 0.55). This finding remained robust across several subgroups of patients and in several sensitivity analyses.
These reductions were associated with a corresponding decline in costs related to HF care, which dropped by $7,433 per patient.
In addition to HF-related hospitalizations, all-cause hospitalizations also declined by roughly 30% after implantation of a PAP sensor (HR, 0.69).
These findings suggest that the reduction in hospitalizations, along with attendant reductions in the costs of care, may be achievable in real-world practice. The 45% drop in HF hospitalizations in this study “compares favorably with the 28% reduction seen with PAP-guided therapy over the same time period in the randomized CHAMPION study that supported the initial FDA approval,” Dr. Desai said.
Moreover, a subgroup of 480 patients had data for 12 months preceding and 12 months following implantation. Analysis of those data showed that the benefits of PAP monitoring to guide HF care “were consistent over longer-term follow-up, with a 34% reduction in HF hospitalizations sustained at 12 months,” he added.
The study had several limitations. It excluded Medicare Part D data, so medication changes related to implantation could not be examined and may have exerted substantial influence on study outcomes.
It also didn’t include the actual PAP-sensor data, “which makes it challenging to confirm that physicians intervened to treat elevated PAPs” and that that intervention is the reason for the study outcomes.
“We were unable to definitively ascertain whether reduced HF hospitalizations are related to undertreatment in the preimplant period or improved treatment in the postimplant period,” Dr. Desai said.
The study was sponsored by Abbott, maker of the CardioMEMS PAP sensor. Dr. Desai and his associates reported ties to Abbott and St. Jude Medical.
FROM ACC 17
Key clinical point: Implantation of a pulmonary artery pressure sensor to guide care in chronic heart failure was associated with a significant reduction in HF hospitalizations and associated substantial costs.
Major finding: The cumulative rate of HF hospitalization was 45% lower during the 6 months after implantation than during the 6 months preceding it (hazard ratio, 0.55).
Data source: A retrospective observational cohort study comparing HF hospitalizations during the 6 months before and the 6 months after PAP sensor implantation in 1,114 Medicare patients.
Disclosures: The study was sponsored by Abbott, maker of the CardioMEMS PAP sensor. Dr. Desai and his associates reported ties to Abbott and St. Jude Medical.
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.
Cell sheet transplantation improves ischemic cardiomyopathy at 1 year
For patients with ischemic cardiomyopathy (ICM), transplanting sheets of autologous myoblasts onto the epicardial surface was safe and led to “marked” improvements in functional and laboratory measures, investigators reported.
However, cell sheet transplantation was much less effective for patients with dilated cardiomyopathy in this phase I trial, wrote Shigeru Miyagawa, MD, PhD, of Osaka (Japan) University, and his associates in the Journal of the American Heart Association. The findings merit additional follow-up in larger clinical studies, the investigators asserted.
Heart failure remains life threatening even with the best approved treatments. Previously, the researchers transplanted scaffold-free sheets of autologous myoblasts derived from skeletal muscle into small and large animals with heart failure and found that this approach healed severely damaged myocardium. Transplantation caused secreted cytokines to induce native regeneration through paracrine effects, Dr. Miyagawa noted in a prior review article (BioMed Research International. 2013. doi: 10.1155/2013/583912).
To evaluate this approach in humans, the researchers transplanted 15 patients with ischemic cardiomyopathy and 12 patients with dilated cardiomyopathy (DCM). Patients were 20-75 years old, had ejection fractions under 35% and New York Heart Association (NYHA) classifications of II or more, and were responding inadequately to standard treatment with a beta-blocker or ACE inhibitor and an angiotensin receptor blocker. The sole intervention was transplantation of the cell sheet over the left ventricular-free wall during left thoracotomy (J Am Heart Assoc. 2017 Apr 5. doi: 10.1161/JAHA.116.003918). There were no major procedure-related complications during follow-up, the researchers said. For patients with ICM, NYHA classifications dropped significantly at 6 months, from 2.9 at baseline to 2.1 at 6 months and 1.9 at 1 year. Six-Minute Walk Test scores improved significantly, from 416 m at baseline to 475 m at 6 months to 484 m at 1 year. Transplantation also led to significant drops in serum brain natriuretic peptide levels (baseline average, 308 pg/mL; 6 months, 191 pg/mL; 1 year, 182 pg/mL). Additionally, ICM patients improved significantly on measures of pulmonary artery pressure, pulmonary capillary wedge pressure, pulmonary vein resistance, and left ventricular wall stress.
In contrast, DCM patients did not significantly improve based on the 6-Minute Walk Test, NYHA classification, or brain natriuretic peptide serum levels. Of 12, 3 progressed to NYHA functional class IV by 1-year follow-up and there were five cardiac deaths. There were no cardiac deaths in the ICM group. “It has been reported that regeneration mechanisms in cell sheet mainly depend on angiogenesis induced by secreted cytokines, so cell-sheet implantation may be more suitable for ICM patients, compared with DCM patients, considering pathophysiological aspects,” the researchers wrote.
The study was funded by grants from Regenerative Medicine for Clinical Application, Health and Labor Sciences Research, and the Japan Agency for Medical Research and Development. The investigators disclosed laboratory funding from Terumo for cooperative research in cell sheet.
For patients with ischemic cardiomyopathy (ICM), transplanting sheets of autologous myoblasts onto the epicardial surface was safe and led to “marked” improvements in functional and laboratory measures, investigators reported.
However, cell sheet transplantation was much less effective for patients with dilated cardiomyopathy in this phase I trial, wrote Shigeru Miyagawa, MD, PhD, of Osaka (Japan) University, and his associates in the Journal of the American Heart Association. The findings merit additional follow-up in larger clinical studies, the investigators asserted.
Heart failure remains life threatening even with the best approved treatments. Previously, the researchers transplanted scaffold-free sheets of autologous myoblasts derived from skeletal muscle into small and large animals with heart failure and found that this approach healed severely damaged myocardium. Transplantation caused secreted cytokines to induce native regeneration through paracrine effects, Dr. Miyagawa noted in a prior review article (BioMed Research International. 2013. doi: 10.1155/2013/583912).
To evaluate this approach in humans, the researchers transplanted 15 patients with ischemic cardiomyopathy and 12 patients with dilated cardiomyopathy (DCM). Patients were 20-75 years old, had ejection fractions under 35% and New York Heart Association (NYHA) classifications of II or more, and were responding inadequately to standard treatment with a beta-blocker or ACE inhibitor and an angiotensin receptor blocker. The sole intervention was transplantation of the cell sheet over the left ventricular-free wall during left thoracotomy (J Am Heart Assoc. 2017 Apr 5. doi: 10.1161/JAHA.116.003918). There were no major procedure-related complications during follow-up, the researchers said. For patients with ICM, NYHA classifications dropped significantly at 6 months, from 2.9 at baseline to 2.1 at 6 months and 1.9 at 1 year. Six-Minute Walk Test scores improved significantly, from 416 m at baseline to 475 m at 6 months to 484 m at 1 year. Transplantation also led to significant drops in serum brain natriuretic peptide levels (baseline average, 308 pg/mL; 6 months, 191 pg/mL; 1 year, 182 pg/mL). Additionally, ICM patients improved significantly on measures of pulmonary artery pressure, pulmonary capillary wedge pressure, pulmonary vein resistance, and left ventricular wall stress.
In contrast, DCM patients did not significantly improve based on the 6-Minute Walk Test, NYHA classification, or brain natriuretic peptide serum levels. Of 12, 3 progressed to NYHA functional class IV by 1-year follow-up and there were five cardiac deaths. There were no cardiac deaths in the ICM group. “It has been reported that regeneration mechanisms in cell sheet mainly depend on angiogenesis induced by secreted cytokines, so cell-sheet implantation may be more suitable for ICM patients, compared with DCM patients, considering pathophysiological aspects,” the researchers wrote.
The study was funded by grants from Regenerative Medicine for Clinical Application, Health and Labor Sciences Research, and the Japan Agency for Medical Research and Development. The investigators disclosed laboratory funding from Terumo for cooperative research in cell sheet.
For patients with ischemic cardiomyopathy (ICM), transplanting sheets of autologous myoblasts onto the epicardial surface was safe and led to “marked” improvements in functional and laboratory measures, investigators reported.
However, cell sheet transplantation was much less effective for patients with dilated cardiomyopathy in this phase I trial, wrote Shigeru Miyagawa, MD, PhD, of Osaka (Japan) University, and his associates in the Journal of the American Heart Association. The findings merit additional follow-up in larger clinical studies, the investigators asserted.
Heart failure remains life threatening even with the best approved treatments. Previously, the researchers transplanted scaffold-free sheets of autologous myoblasts derived from skeletal muscle into small and large animals with heart failure and found that this approach healed severely damaged myocardium. Transplantation caused secreted cytokines to induce native regeneration through paracrine effects, Dr. Miyagawa noted in a prior review article (BioMed Research International. 2013. doi: 10.1155/2013/583912).
To evaluate this approach in humans, the researchers transplanted 15 patients with ischemic cardiomyopathy and 12 patients with dilated cardiomyopathy (DCM). Patients were 20-75 years old, had ejection fractions under 35% and New York Heart Association (NYHA) classifications of II or more, and were responding inadequately to standard treatment with a beta-blocker or ACE inhibitor and an angiotensin receptor blocker. The sole intervention was transplantation of the cell sheet over the left ventricular-free wall during left thoracotomy (J Am Heart Assoc. 2017 Apr 5. doi: 10.1161/JAHA.116.003918). There were no major procedure-related complications during follow-up, the researchers said. For patients with ICM, NYHA classifications dropped significantly at 6 months, from 2.9 at baseline to 2.1 at 6 months and 1.9 at 1 year. Six-Minute Walk Test scores improved significantly, from 416 m at baseline to 475 m at 6 months to 484 m at 1 year. Transplantation also led to significant drops in serum brain natriuretic peptide levels (baseline average, 308 pg/mL; 6 months, 191 pg/mL; 1 year, 182 pg/mL). Additionally, ICM patients improved significantly on measures of pulmonary artery pressure, pulmonary capillary wedge pressure, pulmonary vein resistance, and left ventricular wall stress.
In contrast, DCM patients did not significantly improve based on the 6-Minute Walk Test, NYHA classification, or brain natriuretic peptide serum levels. Of 12, 3 progressed to NYHA functional class IV by 1-year follow-up and there were five cardiac deaths. There were no cardiac deaths in the ICM group. “It has been reported that regeneration mechanisms in cell sheet mainly depend on angiogenesis induced by secreted cytokines, so cell-sheet implantation may be more suitable for ICM patients, compared with DCM patients, considering pathophysiological aspects,” the researchers wrote.
The study was funded by grants from Regenerative Medicine for Clinical Application, Health and Labor Sciences Research, and the Japan Agency for Medical Research and Development. The investigators disclosed laboratory funding from Terumo for cooperative research in cell sheet.
Key clinical point: Transplanting a sheet of autologous myoblasts onto the epicardial surface was safe and was associated with functional and symptomatic improvements in patients with ischemic cardiomyopathy.
Major finding: Patients improved significantly on the 6-Minute Walk Test, New York Heart Classification, and on measures of brain natriuretic peptide, pulmonary artery pressure, pulmonary capillary wedge pressure, pulmonary vein resistance, and left ventricular wall stress. These effects did not extend to patients with dilated cardiomyopathy.
Data source: A phase I trial of 27 patients with ischemic or dilated cardiomyopathy.
Disclosures: The study was funded by grants from Regenerative Medicine for Clinical Application, Health and Labor Sciences Research, and the Japan Agency for Medical Research and Development. The investigators disclosed laboratory funding from Terumo for cooperative research in cell sheet.
Uptake of new heart failure drugs slow despite guidelines
SNOWMASS, COLO. – As William T. Abraham, MD, speaks to colleagues around the country about heart failure therapy, he has noticed that the first-in-class drug ivabradine remains below the radar of most physicians.
“I’ve found that this is an agent that very few people know about, even though it’s been FDA [Food and Drug Administration] approved for about 3 years. It’s used fairly extensively in Europe because that’s where the pivotal SHIFT trial was done, but not very much in the United States,” according to Dr. Abraham, professor of medicine, physiology, and cell biology and director of the division of cardiovascular medicine at Ohio State University in Columbus.
That’s likely to change as word spreads about the May 2016 update of the American College of Cardiology/American Heart Association Guideline for the Management of Heart Failure. The update incorporated evidence-based recommendations on the use of two important new heart failure medications: ivabradine (Corlanor), which received a moderate class IIa recommendation, meaning the drug “should be considered,” and sacubitril/valsartan (Entresto), which received the strongest class I recommendation.
In the right patients, these two oral medications improve heart failure morbidity and mortality significantly beyond what’s achievable with what has been the gold standard, guideline-directed medical therapy. Dr. Abraham described how to get started using the two medications at the Annual Cardiovascular Conference at Snowmass.
Ivabradine
Ivabradine is a selective inhibitor of the sinoatrial pacemaker modulating I(f) current. It acts by slowing the sinus rate without reducing myocardial contractility.
“This agent does one thing and one thing alone: It lowers heart rate,” the cardiologist explained.
And that, he added, was sufficient to significantly reduce the risks of death due to heart failure and recurrent hospitalization for worsening heart failure in the pivotal SHIFT trial.
SHIFT included 6,505 patients with moderate to severe heart failure with reduced left ventricular ejection fraction (LVEF) and a resting heart rate above 70 bpm despite background guideline-directed medical therapy. Participants were randomized double blind to ivabradine titrated to a maximum of 7.5 mg twice daily or placebo and followed for a median of about 23 months. The rate of death due to heart failure was 3% with ivabradine and 5% with placebo, for a statistically significant 26% relative risk reduction favoring ivabradine.
But the drug’s main benefit was in reducing recurrent hospitalizations for heart failure, an endpoint of particular interest to health policy officials given that heart failure hospitalizations chew up a substantial proportion of the Medicare budget. Ivabradine reduced first hospitalizations for heart failure during the study period by 25%, second hospitalizations by 34%, and third hospitalizations by 29% (Eur Heart J. 2012 Nov;33[22]:2813-20).
The ACC/AHA guideline update stresses the importance of reserving ivabradine for heart failure patients whose resting heart rate exceeds 70 bpm, despite being on their maximum tolerated dose of a beta-blocker, Dr. Abraham noted.
Ivabradine is contraindicated in the setting of acute decompensated heart failure, severe liver disease, or hypotension, in patients on any of the numerous agents that strongly inhibit the enzyme cytochrome P450 3A4, and in those who have sick sinus syndrome, have sinoatrial block, or are pacemaker dependent.
Sacubitril/valsartan
Sacubitril inhibits neprilysin, an enzyme that blocks the action of endogenous vasoactive peptides including bradykinin, substance P, and natriuretic peptides, all of which counter important maladaptive mechanisms in heart failure. Sacubitril has been combined with the angiotensin receptor blocker valsartan to form the first-in-class angiotensin receptor neprilysin inhibitor, or ARNI, formerly known as LCZ696 and now marketed as Entresto.
In the pivotal double-blind PARADIGM-HF trial, 8,442 patients with heart failure with reduced ejection fraction were randomized to the ARNI at 200 mg b.i.d. or to enalapril at 10 mg b.i.d. on top of background guideline-directed medical therapy. The trial was stopped early because of evidence of overwhelming benefit: a 20% relative risk reduction in cardiovascular death and a 21% decrease in the risk of heart failure hospitalizations in the sacubitril/valsartan group, as well as significant reductions in heart failure symptoms and physical limitations (N Engl J Med. 2014 Sep 11;371[11]:993-1004).
The updated heart failure guidelines strongly recommend that patients with heart failure should be treated with either an ACE inhibitor, an angiotensin receptor blocker, or an ARNI. Further, patients who remain symptomatic on an ACE inhibitor or angiotensin receptor blocker should be switched to an ARNI; that’s a class Ib recommendation based upon the results of PARADIGM-HF.
In getting started using the ARNI, Dr. Abraham said it’s important to understand as background the selective nature of the PARADIGM-HF study design. During the single-blind run-in period of 5-8 weeks, roughly 10% of patients dropped out because they couldn’t tolerate enalapril at 10 mg b.i.d., and a similar percentage dropped out during the ARNI run-in. Thus, patients who couldn’t tolerate a low dose of an ACE inhibitor weren’t in the study. And patients capable of tolerating guideline-recommended full-dose ACE inhibitor therapy were not specifically sought for participation.
“So there are some unanswered questions about the ARNI. If you’re just getting started with this compound in treating your heart failure patients, my own feeling is you should maybe aim for the type of patient that was included in this trial: patients who could tolerate a moderate dose of an ACE inhibitor and had generally good blood pressure. That’s a great way to begin to get experience with this agent in heart failure,” the cardiologist advised.
He reported serving as a consultant to Abbott Vascular, Medtronic, Novartis, and St. Jude Medical.
SNOWMASS, COLO. – As William T. Abraham, MD, speaks to colleagues around the country about heart failure therapy, he has noticed that the first-in-class drug ivabradine remains below the radar of most physicians.
“I’ve found that this is an agent that very few people know about, even though it’s been FDA [Food and Drug Administration] approved for about 3 years. It’s used fairly extensively in Europe because that’s where the pivotal SHIFT trial was done, but not very much in the United States,” according to Dr. Abraham, professor of medicine, physiology, and cell biology and director of the division of cardiovascular medicine at Ohio State University in Columbus.
That’s likely to change as word spreads about the May 2016 update of the American College of Cardiology/American Heart Association Guideline for the Management of Heart Failure. The update incorporated evidence-based recommendations on the use of two important new heart failure medications: ivabradine (Corlanor), which received a moderate class IIa recommendation, meaning the drug “should be considered,” and sacubitril/valsartan (Entresto), which received the strongest class I recommendation.
In the right patients, these two oral medications improve heart failure morbidity and mortality significantly beyond what’s achievable with what has been the gold standard, guideline-directed medical therapy. Dr. Abraham described how to get started using the two medications at the Annual Cardiovascular Conference at Snowmass.
Ivabradine
Ivabradine is a selective inhibitor of the sinoatrial pacemaker modulating I(f) current. It acts by slowing the sinus rate without reducing myocardial contractility.
“This agent does one thing and one thing alone: It lowers heart rate,” the cardiologist explained.
And that, he added, was sufficient to significantly reduce the risks of death due to heart failure and recurrent hospitalization for worsening heart failure in the pivotal SHIFT trial.
SHIFT included 6,505 patients with moderate to severe heart failure with reduced left ventricular ejection fraction (LVEF) and a resting heart rate above 70 bpm despite background guideline-directed medical therapy. Participants were randomized double blind to ivabradine titrated to a maximum of 7.5 mg twice daily or placebo and followed for a median of about 23 months. The rate of death due to heart failure was 3% with ivabradine and 5% with placebo, for a statistically significant 26% relative risk reduction favoring ivabradine.
But the drug’s main benefit was in reducing recurrent hospitalizations for heart failure, an endpoint of particular interest to health policy officials given that heart failure hospitalizations chew up a substantial proportion of the Medicare budget. Ivabradine reduced first hospitalizations for heart failure during the study period by 25%, second hospitalizations by 34%, and third hospitalizations by 29% (Eur Heart J. 2012 Nov;33[22]:2813-20).
The ACC/AHA guideline update stresses the importance of reserving ivabradine for heart failure patients whose resting heart rate exceeds 70 bpm, despite being on their maximum tolerated dose of a beta-blocker, Dr. Abraham noted.
Ivabradine is contraindicated in the setting of acute decompensated heart failure, severe liver disease, or hypotension, in patients on any of the numerous agents that strongly inhibit the enzyme cytochrome P450 3A4, and in those who have sick sinus syndrome, have sinoatrial block, or are pacemaker dependent.
Sacubitril/valsartan
Sacubitril inhibits neprilysin, an enzyme that blocks the action of endogenous vasoactive peptides including bradykinin, substance P, and natriuretic peptides, all of which counter important maladaptive mechanisms in heart failure. Sacubitril has been combined with the angiotensin receptor blocker valsartan to form the first-in-class angiotensin receptor neprilysin inhibitor, or ARNI, formerly known as LCZ696 and now marketed as Entresto.
In the pivotal double-blind PARADIGM-HF trial, 8,442 patients with heart failure with reduced ejection fraction were randomized to the ARNI at 200 mg b.i.d. or to enalapril at 10 mg b.i.d. on top of background guideline-directed medical therapy. The trial was stopped early because of evidence of overwhelming benefit: a 20% relative risk reduction in cardiovascular death and a 21% decrease in the risk of heart failure hospitalizations in the sacubitril/valsartan group, as well as significant reductions in heart failure symptoms and physical limitations (N Engl J Med. 2014 Sep 11;371[11]:993-1004).
The updated heart failure guidelines strongly recommend that patients with heart failure should be treated with either an ACE inhibitor, an angiotensin receptor blocker, or an ARNI. Further, patients who remain symptomatic on an ACE inhibitor or angiotensin receptor blocker should be switched to an ARNI; that’s a class Ib recommendation based upon the results of PARADIGM-HF.
In getting started using the ARNI, Dr. Abraham said it’s important to understand as background the selective nature of the PARADIGM-HF study design. During the single-blind run-in period of 5-8 weeks, roughly 10% of patients dropped out because they couldn’t tolerate enalapril at 10 mg b.i.d., and a similar percentage dropped out during the ARNI run-in. Thus, patients who couldn’t tolerate a low dose of an ACE inhibitor weren’t in the study. And patients capable of tolerating guideline-recommended full-dose ACE inhibitor therapy were not specifically sought for participation.
“So there are some unanswered questions about the ARNI. If you’re just getting started with this compound in treating your heart failure patients, my own feeling is you should maybe aim for the type of patient that was included in this trial: patients who could tolerate a moderate dose of an ACE inhibitor and had generally good blood pressure. That’s a great way to begin to get experience with this agent in heart failure,” the cardiologist advised.
He reported serving as a consultant to Abbott Vascular, Medtronic, Novartis, and St. Jude Medical.
SNOWMASS, COLO. – As William T. Abraham, MD, speaks to colleagues around the country about heart failure therapy, he has noticed that the first-in-class drug ivabradine remains below the radar of most physicians.
“I’ve found that this is an agent that very few people know about, even though it’s been FDA [Food and Drug Administration] approved for about 3 years. It’s used fairly extensively in Europe because that’s where the pivotal SHIFT trial was done, but not very much in the United States,” according to Dr. Abraham, professor of medicine, physiology, and cell biology and director of the division of cardiovascular medicine at Ohio State University in Columbus.
That’s likely to change as word spreads about the May 2016 update of the American College of Cardiology/American Heart Association Guideline for the Management of Heart Failure. The update incorporated evidence-based recommendations on the use of two important new heart failure medications: ivabradine (Corlanor), which received a moderate class IIa recommendation, meaning the drug “should be considered,” and sacubitril/valsartan (Entresto), which received the strongest class I recommendation.
In the right patients, these two oral medications improve heart failure morbidity and mortality significantly beyond what’s achievable with what has been the gold standard, guideline-directed medical therapy. Dr. Abraham described how to get started using the two medications at the Annual Cardiovascular Conference at Snowmass.
Ivabradine
Ivabradine is a selective inhibitor of the sinoatrial pacemaker modulating I(f) current. It acts by slowing the sinus rate without reducing myocardial contractility.
“This agent does one thing and one thing alone: It lowers heart rate,” the cardiologist explained.
And that, he added, was sufficient to significantly reduce the risks of death due to heart failure and recurrent hospitalization for worsening heart failure in the pivotal SHIFT trial.
SHIFT included 6,505 patients with moderate to severe heart failure with reduced left ventricular ejection fraction (LVEF) and a resting heart rate above 70 bpm despite background guideline-directed medical therapy. Participants were randomized double blind to ivabradine titrated to a maximum of 7.5 mg twice daily or placebo and followed for a median of about 23 months. The rate of death due to heart failure was 3% with ivabradine and 5% with placebo, for a statistically significant 26% relative risk reduction favoring ivabradine.
But the drug’s main benefit was in reducing recurrent hospitalizations for heart failure, an endpoint of particular interest to health policy officials given that heart failure hospitalizations chew up a substantial proportion of the Medicare budget. Ivabradine reduced first hospitalizations for heart failure during the study period by 25%, second hospitalizations by 34%, and third hospitalizations by 29% (Eur Heart J. 2012 Nov;33[22]:2813-20).
The ACC/AHA guideline update stresses the importance of reserving ivabradine for heart failure patients whose resting heart rate exceeds 70 bpm, despite being on their maximum tolerated dose of a beta-blocker, Dr. Abraham noted.
Ivabradine is contraindicated in the setting of acute decompensated heart failure, severe liver disease, or hypotension, in patients on any of the numerous agents that strongly inhibit the enzyme cytochrome P450 3A4, and in those who have sick sinus syndrome, have sinoatrial block, or are pacemaker dependent.
Sacubitril/valsartan
Sacubitril inhibits neprilysin, an enzyme that blocks the action of endogenous vasoactive peptides including bradykinin, substance P, and natriuretic peptides, all of which counter important maladaptive mechanisms in heart failure. Sacubitril has been combined with the angiotensin receptor blocker valsartan to form the first-in-class angiotensin receptor neprilysin inhibitor, or ARNI, formerly known as LCZ696 and now marketed as Entresto.
In the pivotal double-blind PARADIGM-HF trial, 8,442 patients with heart failure with reduced ejection fraction were randomized to the ARNI at 200 mg b.i.d. or to enalapril at 10 mg b.i.d. on top of background guideline-directed medical therapy. The trial was stopped early because of evidence of overwhelming benefit: a 20% relative risk reduction in cardiovascular death and a 21% decrease in the risk of heart failure hospitalizations in the sacubitril/valsartan group, as well as significant reductions in heart failure symptoms and physical limitations (N Engl J Med. 2014 Sep 11;371[11]:993-1004).
The updated heart failure guidelines strongly recommend that patients with heart failure should be treated with either an ACE inhibitor, an angiotensin receptor blocker, or an ARNI. Further, patients who remain symptomatic on an ACE inhibitor or angiotensin receptor blocker should be switched to an ARNI; that’s a class Ib recommendation based upon the results of PARADIGM-HF.
In getting started using the ARNI, Dr. Abraham said it’s important to understand as background the selective nature of the PARADIGM-HF study design. During the single-blind run-in period of 5-8 weeks, roughly 10% of patients dropped out because they couldn’t tolerate enalapril at 10 mg b.i.d., and a similar percentage dropped out during the ARNI run-in. Thus, patients who couldn’t tolerate a low dose of an ACE inhibitor weren’t in the study. And patients capable of tolerating guideline-recommended full-dose ACE inhibitor therapy were not specifically sought for participation.
“So there are some unanswered questions about the ARNI. If you’re just getting started with this compound in treating your heart failure patients, my own feeling is you should maybe aim for the type of patient that was included in this trial: patients who could tolerate a moderate dose of an ACE inhibitor and had generally good blood pressure. That’s a great way to begin to get experience with this agent in heart failure,” the cardiologist advised.
He reported serving as a consultant to Abbott Vascular, Medtronic, Novartis, and St. Jude Medical.
EXPERT ANALYSIS FROM THE CARDIOVASCULAR CONFERENCE AT SNOWMASS
Alpha-blockers deemed safe in heart failure
WASHINGTON – Prescribing alpha-adrenergic blocking agents for treatment of benign prostatic hypertrophy in men with heart failure proved to be not only safe, but also was associated with significantly reduced rates of both heart failure readmission and all-cause mortality in a large retrospective cohort study.
“These findings are associative, not necessarily causative. But the novel association between alpha-blocker treatment and improved outcomes may warrant further study,” Alberta L. Warner, MD, said at the annual meeting of the American College of Cardiology. 
Many men with heart failure also have benign prostatic hypertrophy (BPH), for which they receive treatment with an alpha-blocker. Yet little is known about the impact of this drug class on safety and outcomes in the setting of heart failure. Of note, the use of alpha-blockers for treatment of hypertension was associated with increased risk of new-onset heart failure in the ALLHAT study.
To shed light on the safety of alpha-blockers in patients with prevalent heart failure, Dr. Warner and her coinvestigators analyzed data on nearly 170,000 men with a primary diagnosis of heart failure discharged from Veterans Affairs hospitals in 2002-2015. They determined that fully 28% of them left the hospital on an alpha-blocker. From this pool of nearly 48,000 heart failure patients, they were able to propensity-score match 38,991 on the basis of 54 baseline clinical characteristics to an equal number of VA heart failure patients who weren’t on an alpha-blocker. The study outcomes were time to first readmission for heart failure or all-cause mortality during 2 years of follow-up.
Patients on an alpha-blocker had a 38% heart failure readmission rate at 2 years, compared with 40% in nonusers, for a modest, albeit statistically significant, 6% reduction in relative risk. The all-cause mortality rate also was significantly lower in patients on an alpha-blocker: 40% versus 44%, for a 9% relative risk reduction.
In a subanalysis restricted to the heart failure patients on an alpha-blocker, higher-dose therapy was associated with a significantly lower incidence of all-cause mortality than was a lower-dose alpha-blocker during 2 years of follow-up, with a 9% relative risk reduction. A high-dose alpha-blocker, however, wasn’t significantly more effective than lower-dose therapy in terms of reducing heart failure readmissions, said Dr. Warner, a cardiologist at the Veterans Affairs Greater Los Angeles Healthcare System and the University of California, Los Angeles.
Similarly, patients treated with a nonspecific, peripherally vasoactive alpha-blocker had a significantly lower mortality rate than those on an alpha-1a-adrenergic–specific agent, with a highly significant 15% reduction in relative risk. The type of alpha-blocker, however, didn’t make a significant difference in terms of heart failure readmissions, where both types of agents were similarly better than not being on an alpha-blocker at all, she said.
Eighty-five percent of study participants were on a beta-blocker. Heart failure readmissions and all-cause mortality were significantly lower with alpha-blocker therapy, regardless of whether patients were on background beta-blocker therapy.
One audience member, however, noting that the beta-blocker carvedilol possesses some alpha-blocking effects, asked if outcomes differed depending on whether a patient was on carvedilol or metoprolol.
Dr. Warner replied that those numbers are still being crunched, and that the final answer isn’t in yet, but her preliminary impression is that the benefits of alpha-blocker therapy in terms of both heart failure readmissions and all-cause mortality were attenuated in the patients on carvedilol, possibly due to that beta-blocker’s alpha-blocking properties.
She reported having no financial conflicts regarding the study.
WASHINGTON – Prescribing alpha-adrenergic blocking agents for treatment of benign prostatic hypertrophy in men with heart failure proved to be not only safe, but also was associated with significantly reduced rates of both heart failure readmission and all-cause mortality in a large retrospective cohort study.
“These findings are associative, not necessarily causative. But the novel association between alpha-blocker treatment and improved outcomes may warrant further study,” Alberta L. Warner, MD, said at the annual meeting of the American College of Cardiology.
Many men with heart failure also have benign prostatic hypertrophy (BPH), for which they receive treatment with an alpha-blocker. Yet little is known about the impact of this drug class on safety and outcomes in the setting of heart failure. Of note, the use of alpha-blockers for treatment of hypertension was associated with increased risk of new-onset heart failure in the ALLHAT study.
To shed light on the safety of alpha-blockers in patients with prevalent heart failure, Dr. Warner and her coinvestigators analyzed data on nearly 170,000 men with a primary diagnosis of heart failure discharged from Veterans Affairs hospitals in 2002-2015. They determined that fully 28% of them left the hospital on an alpha-blocker. From this pool of nearly 48,000 heart failure patients, they were able to propensity-score match 38,991 on the basis of 54 baseline clinical characteristics to an equal number of VA heart failure patients who weren’t on an alpha-blocker. The study outcomes were time to first readmission for heart failure or all-cause mortality during 2 years of follow-up.
Patients on an alpha-blocker had a 38% heart failure readmission rate at 2 years, compared with 40% in nonusers, for a modest, albeit statistically significant, 6% reduction in relative risk. The all-cause mortality rate also was significantly lower in patients on an alpha-blocker: 40% versus 44%, for a 9% relative risk reduction.
In a subanalysis restricted to the heart failure patients on an alpha-blocker, higher-dose therapy was associated with a significantly lower incidence of all-cause mortality than was a lower-dose alpha-blocker during 2 years of follow-up, with a 9% relative risk reduction. A high-dose alpha-blocker, however, wasn’t significantly more effective than lower-dose therapy in terms of reducing heart failure readmissions, said Dr. Warner, a cardiologist at the Veterans Affairs Greater Los Angeles Healthcare System and the University of California, Los Angeles.
Similarly, patients treated with a nonspecific, peripherally vasoactive alpha-blocker had a significantly lower mortality rate than those on an alpha-1a-adrenergic–specific agent, with a highly significant 15% reduction in relative risk. The type of alpha-blocker, however, didn’t make a significant difference in terms of heart failure readmissions, where both types of agents were similarly better than not being on an alpha-blocker at all, she said.
Eighty-five percent of study participants were on a beta-blocker. Heart failure readmissions and all-cause mortality were significantly lower with alpha-blocker therapy, regardless of whether patients were on background beta-blocker therapy.
One audience member, however, noting that the beta-blocker carvedilol possesses some alpha-blocking effects, asked if outcomes differed depending on whether a patient was on carvedilol or metoprolol.
Dr. Warner replied that those numbers are still being crunched, and that the final answer isn’t in yet, but her preliminary impression is that the benefits of alpha-blocker therapy in terms of both heart failure readmissions and all-cause mortality were attenuated in the patients on carvedilol, possibly due to that beta-blocker’s alpha-blocking properties.
She reported having no financial conflicts regarding the study.
WASHINGTON – Prescribing alpha-adrenergic blocking agents for treatment of benign prostatic hypertrophy in men with heart failure proved to be not only safe, but also was associated with significantly reduced rates of both heart failure readmission and all-cause mortality in a large retrospective cohort study.
“These findings are associative, not necessarily causative. But the novel association between alpha-blocker treatment and improved outcomes may warrant further study,” Alberta L. Warner, MD, said at the annual meeting of the American College of Cardiology.
Many men with heart failure also have benign prostatic hypertrophy (BPH), for which they receive treatment with an alpha-blocker. Yet little is known about the impact of this drug class on safety and outcomes in the setting of heart failure. Of note, the use of alpha-blockers for treatment of hypertension was associated with increased risk of new-onset heart failure in the ALLHAT study.
To shed light on the safety of alpha-blockers in patients with prevalent heart failure, Dr. Warner and her coinvestigators analyzed data on nearly 170,000 men with a primary diagnosis of heart failure discharged from Veterans Affairs hospitals in 2002-2015. They determined that fully 28% of them left the hospital on an alpha-blocker. From this pool of nearly 48,000 heart failure patients, they were able to propensity-score match 38,991 on the basis of 54 baseline clinical characteristics to an equal number of VA heart failure patients who weren’t on an alpha-blocker. The study outcomes were time to first readmission for heart failure or all-cause mortality during 2 years of follow-up.
Patients on an alpha-blocker had a 38% heart failure readmission rate at 2 years, compared with 40% in nonusers, for a modest, albeit statistically significant, 6% reduction in relative risk. The all-cause mortality rate also was significantly lower in patients on an alpha-blocker: 40% versus 44%, for a 9% relative risk reduction.
In a subanalysis restricted to the heart failure patients on an alpha-blocker, higher-dose therapy was associated with a significantly lower incidence of all-cause mortality than was a lower-dose alpha-blocker during 2 years of follow-up, with a 9% relative risk reduction. A high-dose alpha-blocker, however, wasn’t significantly more effective than lower-dose therapy in terms of reducing heart failure readmissions, said Dr. Warner, a cardiologist at the Veterans Affairs Greater Los Angeles Healthcare System and the University of California, Los Angeles.
Similarly, patients treated with a nonspecific, peripherally vasoactive alpha-blocker had a significantly lower mortality rate than those on an alpha-1a-adrenergic–specific agent, with a highly significant 15% reduction in relative risk. The type of alpha-blocker, however, didn’t make a significant difference in terms of heart failure readmissions, where both types of agents were similarly better than not being on an alpha-blocker at all, she said.
Eighty-five percent of study participants were on a beta-blocker. Heart failure readmissions and all-cause mortality were significantly lower with alpha-blocker therapy, regardless of whether patients were on background beta-blocker therapy.
One audience member, however, noting that the beta-blocker carvedilol possesses some alpha-blocking effects, asked if outcomes differed depending on whether a patient was on carvedilol or metoprolol.
Dr. Warner replied that those numbers are still being crunched, and that the final answer isn’t in yet, but her preliminary impression is that the benefits of alpha-blocker therapy in terms of both heart failure readmissions and all-cause mortality were attenuated in the patients on carvedilol, possibly due to that beta-blocker’s alpha-blocking properties.
She reported having no financial conflicts regarding the study.
Key clinical point:
Major finding: The risk of all-cause mortality in heart failure patients on an alpha-blocker was 9% lower than in extensively matched controls during 2 years of follow-up.
Data source: This retrospective cohort study included 38,991 heart failure patients taking an alpha-blocker for benign prostatic hypertrophy who were propensity matched on 54 clinical characteristics to an equal number of heart failure controls not on the medication.
Disclosures: The study presenter reported having no financial conflicts.
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.