TY - JOUR
T1 - Addition of angiotensin II receptor blockade to maximal angiotensin- converting enzyme inhibition improves exercise capacity in patients with severe congestive heart failure
AU - Hamroff, Glenn
AU - Katz, Stuart D.
AU - Mancini, Donna
AU - Blaufarb, Ira
AU - Bijou, Rachel
AU - Patel, Rajoo
AU - Jondeau, Guillaume
AU - Olivari, Maria Teresa
AU - Thomas, Sylvia
AU - Le Jemtel, Thierry H.
PY - 1999/3/2
Y1 - 1999/3/2
N2 - 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.
AB - 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.
KW - Angiotensin
KW - Exercise
KW - Heart failure
KW - Trials
UR - http://www.scopus.com/inward/record.url?scp=0033514910&partnerID=8YFLogxK
U2 - 10.1161/01.CIR.99.8.990
DO - 10.1161/01.CIR.99.8.990
M3 - Article
C2 - 10051289
AN - SCOPUS:0033514910
SN - 0009-7322
VL - 99
SP - 990
EP - 992
JO - Circulation
JF - Circulation
IS - 8
ER -