HEAAL: High-dose losartan associated with reduced mortality, HF hospitalization

An up-titration of the angiotensin receptor blocker in patients with HF bestowed incremental clinical benefit.

American Heart Association Scientific Sessions 2009

A higher dose of the angiotensin receptor-blocker losartan (Cozaar, Merck) was associated with a reduction in all-cause mortality and HF hospitalization, according to new study results.

Researchers enrolled 3,846 patients with left ventricular ejection fraction ≤40% and NYHA Class II to IV HF in the study and randomly assigned them to receive either a high dose of losartan at 150 mg (n=1,921) or a low dose of losartan at 50 mg (n=1,913). Six patients were excluded from the final analysis due to poor data quality, resulting in a final study population of 3,834. The primary study endpoint was death or hospitalization from HF. The patients were followed for a median of 4.7 years.

The researchers reported that the primary endpoint of all-cause mortality or HF hospitalization was reduced in patients receiving the high-dose losartan vs. the low-dose losartan at four years (HR=0.90; 95% CI, 0.82-0.99). A total of 828 patients in the high-dose group and 889 in the low-dose group experienced the endpoint of death or HF hospitalization (P=.027).

There were also reductions in the secondary endpoints of HF hospitalization (P=.025) and CV hospitalization (P=.023) in the high-dose losartan group. A trend toward reduced death or CV hospitalization was also reported in the high-dose group (P=.068). Adverse events in the high-dose losartan group included elevated rates of renal impairment (P<.001), hypotension (P=.002) and hyperkalemia (P<.001).

“In patients with HF, reduced LVEF and ACE inhibitor intolerance, incremental value is derived from up-titrating angiotensin receptor-blocker doses to levels demonstrated to confer benefit on clinical outcomes,” Marvin Konstam, MD, a professor of medicine at Tufts University School of Medicine, said during his presentation. “Our findings confirm the view that incremental inhibition of the renin-angiotensin system, within the range of explored in HF trials to date, achieves a progressively favorable impact on clinical outcomes.” – by Eric Raible

A higher dose of losartan, as shown in the HEAAL study, provided incremental benefit. This also means that all ongoing losartan treatments need to be reevaluated as the low dose is not effective on clinical outcomes, and we have a dose that is more effective. It also emphasizes the need to up-titrate angiotensin receptor-blockers in HF to documented dose levels, which, in these trials, have been fairly high.

– Karl Swedberg, MD

Professor of Medicine, Göteborg University
Göteborg, Sweden

For more information:

Konstam M. LBCT 04 #148. Presented at: American Heart Association Scientific Sessions; Nov. 14-18, 2009; Orlando, Fla.