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.
In his year-in-review lecture, the cardiologist highlighted five important advances, five big disappointments, and a pair of randomized trials of treatment of sleep apnea in heart failure which, while negative overall, showed a strong positive signal that’s now being followed up.
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;373:2117-28).
“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;376:440-50).
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;388:2895-903).
“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;314:2251-62), 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.
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