Captopril. A review of its pharmacology and therapeutic efficacy after myocardial infarction and in ischaemic heart disease.
Captopril is an angiotensin converting enzyme (ACE) inhibitor which has been used extensively in the treatment of patients with hypertension and congestive heart failure. In recent years, animal and human studies have demonstrated that captopril attenuates left ventricular remodelling (structural changes and enlargement) which occurs after myocardial infarction, and can lead to left ventricular dysfunction and increased risk of death. Subsequently, large clinical trials have shown reduced mortality and morbidity in patients receiving captopril or other ACE inhibitors (in addition to standard therapy) after acute myocardial infarction. Results of the 4th International Study of Infarct Survival (ISIS-4), a factorial trial which randomised more than 58,000 patients, indicate that captopril, initiated within 24 hours of myocardial infarction and titrated to 50 mg twice daily for 1 month, significantly reduced overall mortality at 5 weeks after randomisation compared with placebo (7.19 vs 7.69%; p = 0.02). This corresponds to an absolute benefit of 5 lives saved per 1000 patients treated with captopril over this period. Furthermore, the survival advantage appeared to be maintained at 1 year post-infarction. Although both high- and low-risk patients were included in the ISIS-4 trial, the greatest survival benefit of captopril occurred in patients at greater risk of mortality, such as those with signs of heart failure or previous infarction. A significant relative reduction in overall mortality of 19% was seen in patients with left ventricular dysfunction (but not overt heart failure or ongoing ischaemia) after acute myocardial infarction treated with captopril in the Survival and Ventricular Enlargement (SAVE) study. Captopril was started within 3 to 16 days after myocardial infarction and titrated to 50 mg 3 times daily for a mean duration of 42 months. In this high-risk group of patients, approximately 40 to 50 lives were saved per 1000 patients treated with captopril over this period. This was similar to survival benefits demonstrated with other ACE inhibitors following acute myocardial infarction in high-risk patients in other large randomised trials. Cost-effectiveness analyses using data from the SAVE trial indicate that captopril compares favourably with other interventions used for survivors of myocardial infarction. In general, captopril was well tolerated by patients in SAVE, ISIS-4 and other studies in this clinical setting. Thus, when added to standard therapy after acute myocardial infarction, early or late administration of captopril improves survival and reduces cardiovascular morbidity, particularly in selected high-risk patients.(ABSTRACT TRUNCATED AT 400 WORDS)
Adis International Limited, Auckland, New Zealand.
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Plosker
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McTavish
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use*; D000818:Animals; D002216:Captopril / Q000494:pharmacology* / Q000627:therapeutic use*; D006801:Humans; D009203:Myocardial Infarction / Q000188:drug therapy*; D017202:Myocardial Ischemia / Q000188:drug therapy*
D000806:Angiotensin-Converting Enzyme Inhibitors; D002216:Captopril