The use of the direct renin inhibitor aliskiren failed to improve outcomes for patients with stable heart failure at 6 months or at 12 months, researchers reported here at the annual scientific sessions of the American College of Cardiology.
After a year of treatment, 35% of the aliskiren patients had met the primary endpoint of cardiovascular-caused death or heart failure-related hospitalizations compared with 37.3% of patients treated with best supportive care plus placebo (P=0.36), Mihai Gheorghiade, MD, professor of medicine and surgery at Northwestern University in Chicago, said in a late-breaker oral presentation.
In the aliskiren arm of the trial, 126 cardiovascular deaths were observed and 212 heart failure hospitalizations were recorded at 12 months; there were 137 cardiovascular deaths and 224 heart failure hospitalizations among patients assigned to placebo, Gheorghiade said.
The 6-month figures also failed to distinguish aliskiren from placebo: In the active drug arm 77 cardiovascular deaths and 153 hospitalizations were observed; in the placebo arm, there were 85 cardiovascular deaths and 155 heart failure hospitalizations (P=.41).
“What is troubling about this study,” Gheorghiade said, “was that these patients were very well treated with background medications and yet in 1 year we are experiencing these high mortality rates.” There were 263 cardiovascular deaths among the 1,615 people — 808 on aliskiren and 807 on placebo — included in the study analysis.
All-cause mortality was 144 in the aliskiren group (17.8%) and 148, or 18.3%, of the placebo group (P=0.98).
“We need to find better treatments for these patients,” he said.
Aliskiren, however, does not appear to be the solution, said Elliott Antman, MD, professor of medicine at Brigham & Women’s Hospital and Harvard. “These results are not particularly promising for aliskiren,”, noting that the antihypertensive agent is not used often in clinical practice. He uses the drug only as an add-on treatment for patients who cannot achieve target blood pressure goals on two or three agents.
Gheorghiade noted in a press briefing that diabetic patients did worse on aliskiren, but those without diabetes did better. “I think that information supports the need to attempt a clinical trial in heart failure patients who are not diabetic,”.
However Antman was skeptical about the diabetes data. “I bet this doesn’t pan out in the long run,” he said. “But we will see.” While there were trends in opposite directions among this group of patients, he said a possibility is that there really is no difference, since neither subset analysis is statistically significant.
This so-called ASTRONAUT trial, published simultaneously in the Journal of the American Medical Association, noted that the rates of hyperkalemia, hypotension, and renal impairment/renal failure were higher in the aliskiren group compared with placebo.
The patients analyzed for the trial had a mean age of 64.6; more than 75% were men, mean body mass index was 27.2, and 70.6% were whites.
Gheorghiade noted that the patients were generally well treated for heart failure with decreased left ventricular function: 95.8% were on diuretics; 84.2% were on angiotensin-converting enzyme inhibitors or angiotensin receptor blockers; 82.5% were on beta-blockers; 15.7% of the patients were on implantable cardioverter-defibrillators; and 11.2% were on permanent pacemakers.
Gheorghiade disclosed commercial interests with Bayer Schering Pharma AG,DebioPharm S.A., Medtronic, Novartis Pharma AG, Otsuka Pharmaceuticals, Sigma Tau, Solvay Pharmaceuticals, and Pericor Therapeutics.
Antman disclosed commercial interests with Eli Lilly and Company, Daiichi Sankyo, sanofi-aventis, Novartis Pharmaceuticals, Millennium Pharmaceuticals, Beckman Coulter, Bayer Healthcare, Nuvelo, Ortho-Clinical Diagnostics, Amgen, Inotek Pharmaceuticals, Pfizer, CV Therapeutics, Integrated Therapeutics Corporation, Roche Diagnostics, Roche Diagnostics GmbH, Schering-Plough Research Institute, The National Institutes of Health, GlaxoSmithKline, Accumetrics, Bristol-Myers Squibb Pharmaceutical Research Institute, Sanofi-Synthelabo Recherche, AstraZeneca Pharmaceuticals, Merck & Co, and Biosite.
Gheorghiade M, et al “Effect of aliskiren on postdischarge mortality and heart failure readmissions among patients hospitalized for heart failure: The ASTRONAUT randomized trial” JAMA 2013; DOI: 10.1001/jama.2013.1954.