Abstract
Background: Angiotensin I–converting enzyme inhibition (ACEI) and angiotensin II AT1-receptor blockade are effective at improving survival and limiting cardiac remodeling in the rat model of postischemic heart failure. Whether their combination yields additive/synergistic effects is unknown. Methods and Results: Rats underwent coronary artery ligation and 7 days later were treated orally for 9 months with placebo (controls), 5 mg/kg valsartan, 1 mg/kg enalapril (doses submaximally effective at reducing mortality in the experimental model used), or 5 mg/kg valsartan and 1 mg/kg enalapril combined. Compared with controls, valsartan, enalapril, and their combination decreased mortality by 40% (P =.006), 21% (P =.065), and 33% (P =.032), respectively, but there was no significant difference between the 3 treatments. At the doses used, valsartan, but neither enalapril nor the combination, slightly limited cardiac hypertrophy and fibrosis development and reduced left ventricular end-diastolic pressure as assessed in the surviving animals at 9 months. Conclusions: In experimental chronic heart failure in rats, valsartan reduces mortality similar to other AT1-receptor blockers and a combination of AT1-receptor blockade (valsartan) and ACEI (enalapril) at submaximal doses does not exert additive/synergistic beneficial effects on mortality.
Published Version
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