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Long-term treatment of severe chronic heart failure with captopril: a double-blind, randomized, placebo-controlled,
Insights
Captopril significantly improved heart function in patients with severe heart failure by reducing filling pressures and increasing cardiac output. This ACE inhibitor also enhanced renal blood flow and reduced norepinephrine levels, demonstrating its efficacy in managing advanced heart failure.
Area of Science:
- Cardiology
- Pharmacology
- Nephrology
Background:
- Severe heart failure (NYHA classes III-IV) poses significant challenges in management.
- Current treatments with digitalis and diuretics may not fully address all aspects of the condition.
Purpose of the Study:
- To evaluate the efficacy of captopril as an add-on therapy in patients with severe heart failure.
- To assess the impact of captopril on hemodynamic parameters, cardiac output, renal blood flow, and neurohormonal activity.
Main Methods:
- A randomized, double-blind, placebo-controlled study over 6 months.
- 23 patients with severe heart failure received either captopril (n=12) or placebo (n=11) in addition to digitalis and diuretics.
- Measurements included left-ventricular filling pressure, cardiac index, renal blood flow (Hippuran clearance), peripheral vascular resistance, heart rate, blood pressure, heart volume, and plasma norepinephrine.
Main Results:
- Captopril significantly reduced left-ventricular filling pressures at rest and during exercise compared to placebo.
- Cardiac index increased substantially with captopril, indicating improved cardiac output, while renal blood flow improved significantly.
- Peripheral vascular resistance decreased markedly with captopril, and plasma norepinephrine levels were reduced, suggesting inhibition of the renin-angiotensin system and sympathetic activity.
Conclusions:
- Captopril demonstrates significant benefits in severe heart failure by improving hemodynamic function, enhancing cardiac output and renal perfusion.
- The drug's efficacy is attributed to its inhibitory effects on the renin-angiotensin system and sympathetic nervous system, leading to myocardial unloading.
- Captopril offers a valuable therapeutic option for advanced heart failure, improving clinical status and potentially reducing mortality.
Abstract:
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 less than 0.01 (p less than 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 1/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 less than 0.02 (p less than 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 less than 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-5, from 1,834 to 1,710; p less than 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 less than 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.