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Difference in mortality between patients treated with captopril or enalapril in the Xamoterol in Severe Heart Failure
H Pouleur1, M F Rousseau, C Oakley
1University of Louvain Medical School, Brussels, Belgium.
Insights
In severe heart failure patients, captopril showed lower survival rates than enalapril, possibly due to suboptimal dosing affecting angiotensin-converting enzyme inhibition. Further trials should explore optimal dosing for full therapeutic benefit.
Area of Science:
- Cardiology
- Pharmacology
- Clinical Trials
Background:
- Heart failure (HF) management often involves angiotensin-converting enzyme (ACE) inhibitors.
- Comparing the efficacy of different ACE inhibitors in severe HF is crucial for optimizing patient outcomes.
Purpose of the Study:
- To compare the survival rates of patients with severe heart failure treated with captopril versus enalapril.
- To investigate the potential impact of dosing regimens on the efficacy of ACE inhibitors in severe heart failure.
Main Methods:
- A double-blind, placebo-controlled, multinational trial involving 290 patients on captopril and 217 on enalapril.
- Patients were randomized to receive either xamoterol or placebo over a 100-day follow-up period.
- Survival probability was assessed, and patient characteristics and treatment regimens were analyzed.
Main Results:
- The captopril group exhibited a lower cumulative survival probability (90.3%) compared to the enalapril group (97.2%).
- This difference in mortality was observed across various patient subsets and countries, irrespective of HF severity indexes.
- Suboptimal captopril dosing or administration schedule may have led to reduced ACE inhibition compared to enalapril.
Conclusions:
- Captopril, under the trial's dosing conditions, was associated with lower survival in severe heart failure patients compared to enalapril.
- Optimizing the dosing regimen and ensuring adequate circadian ACE inhibition are critical for maximizing the therapeutic benefits of ACE inhibitors in heart failure management.
- Future research should focus on determining the necessary extent of ACE inhibition for optimal HF treatment outcomes.
Abstract:
The double-blind, placebo-controlled, multinational trial Xamoterol in Severe Heart Failure randomized 290 patients treated with captopril and 217 treated with enalapril to xamoterol or placebo. At the end of the 100-day follow-up period, the cumulative probability of survival in patients with coronary artery disease or with dilated cardiomyopathy decreased in the captopril group (90.3%) when compared with the enalapril group (97.2%). The excess mortality in the captopril group could not be related to the indexes of the severity of heart failure, such as baseline exercise duration, functional class, cardiothoracic ratio, ejection fraction or dose of diuretic drugs. Furthermore, the excess in mortality was seen in all subsets of patients examined as well as across countries. Examination of the dosing regimen used, however, suggests that insufficient daily dosage of captopril or the inadequate schedule of administration, or both, might be responsible for different degrees of angiotensin-converting enzyme inhibition between the enalapril and captopril groups and hence for the difference in mortality. It is important in future clinical trials to determine to what extent complete circadian angiotensin-converting enzyme inhibition is necessary to provide the full benefit of this therapy in heart failure.