Long-Term Treatment of Severe Chronic Heart Failure with Captopril: A Double-Blind, Randomized, Placebo-Controlled, Long-Term Study

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Twenty-three patients with severe heart failure (NYHA classes III and IV) on treatment with digitalis and diuretics were additionally treated in a randomized double-blind study over a 6-month period with captopril (n = 12; mean daily dose 84 mg) or a placebo (n = 11) and were then reexamined. In the captopril group, the left-ventricular filling pressure decreased by 9 mm Hg (from 23 to 14) at rest and 6 mm Hg (from 35 to 29) during exercise. In the placebo group, there was an increase of 4 mm Hg (from 25 to 29) at rest and 7 mm Hg (from 33 to 40) during exercise;p < 0.01 (p < 0.01). In the captopril group, the cardiac index at rest increased 0.7 1/min/m2 (from 2.1 to 2.8) and during exercise 1.2 l/min/m2 (from 2.8 to 4.0). In the placebo group, the increase in cardiac index was considerably less pronounced at rest (= 0.2 1/min/m2; from 1.9 to 2.1) and during exercise (=0.1 1/min/m2; from 2.7 to 2.8);p < 0.02 (p < 0.01). The improved cardiac output had a beneficial effect on the renal blood flow. Hippuran clearance increased by 46 ml/min (from 271 to 318). whereas in the control group it decreased 25 ml/min (from 259 to 234) (p < 1.02). Both the heart rate and the arterial blood pressure remained constant, whereas the decrease in peripheral vascular resistance was definitely more pronounced in the captopril group (= 562 dyne X s X cm−5, from 1,841 to 1,279) than in the placebo group (= 123 dyne X s X cm“‘, from 1,834 to 1,710; p < 0.02). The heart volume, assessed radiographically, increased slightly in the placebo group, and the left-ventricular end-diastolic diameter remained constant in both groups. In the course of the study, two patients died in the captopril group and three in the placebo group. After six months, eight patients in the captopril group and three in the placebo group had improved by at least one NYHA category. The beneficial effects of captopril are due to its inhibitory effect on the renin-angiotensin system as well as to the inhibition of sympathetic stimulation. Consequently, in the captopril group the quantity of plasma norepinephrine decreased by 188 ng/ml (from 430 to 618);p < 0.03. The indirect vasodilation caused by this mechanism leads to persistent unloading of the myocardium and an improvement in heart failure without loss of action by counterregulatory mechanisms.

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