CAPTOPRIL - A REVIEW OF ITS PHARMACOLOGY AND THERAPEUTIC EFFICACY AFTER MYOCARDIAL-INFARCTION AND IN ISCHEMIC-HEART-DISEASE

Captopril is an angiotensin converting enzyme (ACE) inhibitor which ha s been used extensively in the treatment of patients with hypertension and congestive heart failure. In recent years, animal and human studi es have demonstrated that captopril attenuates left ventricular remode lling (structural changes and enlargement) which occurs after myocardi al infarction, and can lead to left ventricular dysfunction and increa sed risk of death. Subsequently, large clinical trials have shown redu ced mortality and morbidity in patients receiving captopril or other A CE inhibitors (in addition to standard therapy) after acute myocardial infarction. Results of the 4th International Study of lnfarct Surviva l (ISIS-4), a factorial trial which randomised more than 58 000 patien ts, indicate that captopril, initiated within 24 hours of myocardial i nfarction and titrated to 50 mg twice daily for I month, significantly reduced overall mortality at 5 weeks after randomisation compared wit h placebo (7.19 vs 7.69%; p = 0.02). This corresponds to an absolute b enefit of 5 lives saved per 1000 patients treated with captopril over this period. Furthermore, the survival advantage appeared to be mainta ined at I year post-infarction. Although both high- and low-risk patie nts were included in the ISIS-4 trial, the greatest survival benefit o f captopril occurred in patients at greater risk of mortality, such as those with signs of heart failure or previous infarction. A significa nt relative reduction in overall mortality of 19% was seen inpatients with left ventricular dysfunction (but not overt heart failure or ongo ing ischaemia) after acute myocardial infarction treated with captopri l in the Survival and Ventricular Enlargement (SAVE) study. Captopril was started within 3 to 16 days after myocardial infarction and titrat ed to 50 mg 3 times daily for a mean duration of 42 months. In this hi gh-risk group of patients, approximately 40 to 50 lives were saved per 1000 patients treated with captopril over this period. This was simil ar to survival benefits demonstrated with other ACE inhibitors followi ng acute myocardial infarction in high-risk patients in other large ra ndomised trials. Cost-effectiveness analyses using data from the SAVE trial indicate that captopril compares favourably with other intervent ions used for survivors of myocardial infarction. In general, captopri l was well tolerated by patients in SAVE, ISIS-4 and other studies in this clinical setting. Thus, when added to standard therapy after acut e myocardial infarction, early or late administration of captopril imp roves survival and reduces cardiovascular morbidity, particularly in s elected high-risk patients. In the US, captopril has been approved for use in patients with left ventricular dysfunction after myocardial in farction (the study population of the SAVE trial). Other patient group s also likely to benefit from captopril therapy after myocardial infar ction are clinically stable patients with clinical signs of congestive heart failure and those with an anterior infarction or a previous inf arction; however it is noteworthy that captopril has demonstrated surv ival benefits in large studies of relatively unselected patient popula tions (i. e. including both high- and low-risk patients). Accordingly, captopril represents an important advance in the management of patien ts after acute myocardial infarction.