Comparison of Changes in Respiratory Function and Exercise Oxygen Uptake With Losartan Versus Enalapril in Congestive Heart Failure Secondary to Ischemic or Idiopathic Dilated Cardiomyopathy

Abstract

In congestive heart failure (CHF), some of the effects of angiotensin-converting enzyme (ACE) inhibitors, such as an increase in exercise oxygen uptake (VO₂), are mediated through prostaglandins. Angiotensin (AT₁) receptor blockers apparently do not share potentiation of this biosystem. We tested whether losartan improves exercise VO₂ in CHF and if the effect is the same as for enalapril. Sixteen men with CHF and 8 volunteers, all nonsmokers and not taking ACE, AT₁ receptor, or cyclooxygenase inhibitors, were randomized to receive placebo, enalapril (10 mg 2 times daily), losartan (50 mg/day), each of these 2 drugs plus aspirin (325 mg/day), aspirin, or the same preparations in a reverse order, each for 3 weeks, with a 3-week washout period between treatments. Pulmonary function and VO₂ were assessed at the end of each treatment. In CHF, losartan and enalapril caused a similar improvement of VO₂ and exercise tolerance, which was absent in controls and was counteracted by aspirin (prostaglandin inhibition) when obtained with enalapril and not with losartan. While on enalapril, we also detected an increase in the diffusing lung capacity for carbon monoxide, which correlated with changes in VO₂ and was antagonized by aspirin, suggesting the possibility that a prostaglandin-mediated functional improvement of the alveolar capillary membrane contributes to the rise in VO₂. Thus, losartan is as effective as enalapril for exercise VO₂ and exercise tolerance, but the mechanism seems to be dissociated from a prostaglandin biosystem activation. Losartan may represent an advancement in CHF because its efficacy on VO₂ is similar to that of enalapril, but is not antagonized by aspirin.