High dose ARBs maximise benefits in heart failure

Several studies have determined the efficacy of angiotensin-receptor blockers (ARBs) for treating heart failure. However, the relationship between high and low doses and clinical outcomes has been poorly studied to date.
In this large double-blind study undertaken in 255 centres across 30 countries, 3846 patients with NYHA heart failure class II-IV, a left-ventricular ejection fraction of 40% or less, and intolerance to ACE inhibitors were randomly assigned to either losartan 150mg od (n=1927) or 50mg daily (n=1919). The primary endpoint was death or admission for heart failure. Analysis was by intention to treat.
The median follow-up in each group was 4.7 years. 828 (43%) of patients in the 150mg group versus 889 (46%) in the 50mg group died or were admitted for heart failure (hazard ratio 0.90; p=0.027). For the two primary endpoint components, no difference was seen in deaths (635 patients in the 150mg group vs. 665, hazard ratio 0.94; p=0.24), however 450 versus 503 patients were admitted for heart failure (hazard ratio 0.87; p=0.025). However, renal impairment, hypotension, and hyperkalaemia were more common in the 150mg group, but did not lead to significantly more treatment discontinuations.
Conclusions:
Losartan 150mg, as compared to a 50mg dose, reduced the rate of death or admission for heart failure in patients with heart failure, reduced ejection fraction, and intolerance to ACE inhibitors. ARB doses can be uptitrated for clinical benefit in patients with impaired ventricular function.
• Konstam MA, Neaton JD, Dickstein K et al. Effect of high-dose versus low-dose losartan on clinical outcomes in patients with heart failure (HEAAL study): a randomised, double-blind trial. Lancet 2009; 374: 1840-1848.

Figure 1: Kaplan-Meier curves for patients given 50mg vs 150mg losartan
http://heart.bmj.com/site/misc/April2.pdf

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