By Bruce Sylvester
ORLANDO, Fla -- November 18, 2009 -- A higher dose of the angiotensin-receptor blocker (ARB) losartan appears to be more effective than a lower dose in the treatment of patients with heart failure, according to trial data presented at the American Heart Association (AHA) Scientific Sessions 2009.
Researchers reported their findings from the Comparison of Low-Dose Versus High-Dose Losartan Treatment on Morbidity and Mortality in Angiotensin Converting Enzyme Inhibitor-Intolerant Patients With Heart Failure and Reduced Left Ventricular Ejection Fraction (HEAAL) study here on November 17.
"HEALL was the first study to investigate the dose response of an ARB on clinical outcomes in patients with heart failure," said lead investigator Marvin Konstam, MD, Tufts University School of Medicine, Boston, Massachusetts. "Compared with losartan 50 mg daily, losartan 150 mg daily significantly reduced the rate of the combined endpoint of all-cause mortality or heart failure hospitalisation," he added.
Eligibility for the trial included a diagnosis of heart failure, left-ventricular ejection fraction of 40% or less, and intolerance to angiotensin-converting enzyme inhibitor therapy.
The investigators randomised 3,834 subjects to either losartan 150 mg daily (n = 1,921) or losartan 50 mg daily (n = 1,913). The median follow-up was 4.7 years.
Baseline demographics were similar for both arms, with a mean age of about 64 years in both groups and about 70% males in each group.
Dr. Konstam reported that 1,710 subjects had primary-endpoint events (combined all-cause mortality or heart failure hospitalisation) during the follow-up period. There were 828 such events in the high-dose group and 889 in the low-dose group. The difference was statistically significant (P = .027), and translated into a 10% risk reduction for the higher dose versus the lower dose, attributable mostly to a 13% reduction in the risk of heart failure hospitalisation.
There was no difference in all-cause mortality.
Dr. Konstam also reported that the 150-mg losartan dosing was associated with higher rates of hypotension, hyperkalaemia, and renal impairment, but that the overall rates of clinically relevant adverse events were small.
"The findings confirm the view that incremental inhibition of the renin-angiotensin system, within the range explored in heart failure trials to date, achieves a progressively favourable impact on clinical outcomes," he concluded.
Funding for this study was provided by Merck Inc.
[Presentation title: Comparison of Low-Dose Versus High-Dose Losartan Treatment on Morbidity and Mortality in Angiotensin Converting Enzyme Inhibitor-Intolerant Patients With Heart Failure and Reduced Left Ventricular Ejection Fraction: Results of the HEAAL Study. Abstract 09-LBCT-19918-AHA]
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