Addition of angiotensin II receptor blockade to maximal angiotensin- converting enzyme inhibition improves exercise capacity in patients with severe congestive heart failure

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 (AT₁) receptor blockade and ACE inhibition more completely suppresses the activated renin-angiotensin system than either intervention alone in sodium-depleted normal individuals. Whether AT₁ 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 (V̇O₂) during symptom-limited treadmill exercise and NYHA functional class were determined at baseline and after 3 and 6 months of double-blind therapy. Peak V̇O₂ 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.