Addition of Angiotensin II Receptor Blockade to Maximal Angiotensin-Converting Enzyme Inhibition Improves Exercise Capacity in Patients With Severe Congestive Heart Failure

Abstract

Background —Incomplete suppression of the renin-angiotensin system during long-term ACE inhibition may contribute to symptomatic deterioration in patients with severe congestive heart failure (CHF). Combined angiotensin II type I (AT 1 ) receptor blockade and ACE inhibition more completely suppresses the activated renin-angiotensin system than either intervention alone in sodium-depleted normal individuals. Whether AT 1 receptor blockade with losartan improves exercise capacity in patients with severe CHF already treated with ACE inhibitors is unknown. Methods and Results —Thirty-three patients with severe CHF despite treatment with maximally recommended or tolerated doses of ACE inhibitors were randomized 1:1 to receive 50 mg/d losartan or placebo for 6 months in addition to standard therapy in a multicenter, double-blind trial. Peak aerobic capacity (V̇ o 2 ) during symptom-limited treadmill exercise and NYHA functional class were determined at baseline and after 3 and 6 months of double-blind therapy. Peak V̇ o 2 at baseline and after 3 and 6 months were 13.5±0.6, 15.1±1.0, and 15.7±1.1 mL · kg −1 · min −1 , respectively, in patients receiving losartan and 14.1±0.6, 14.3±0.9, and 13.6±1.1 mL · kg −1 · min −1 , respectively, in patients receiving placebo ( P <0.02 for treatment group–by-time interaction). Functional class improved by at least one NYHA class in 9 of 16 patients receiving losartan and 1 of 17 patients receiving placebo. Conclusions —Losartan enhances peak exercise capacity and alleviates symptoms in patients with CHF who are severely symptomatic despite treatment with maximally recommended or tolerated doses of ACE inhibitors.