ANGIOTENSIN-CONVERTING ENZYME-INHIBITION AFTER MYOCARDIAL-INFARCTION - THE TRANDOLAPRIL CARDIAC EVALUATION STUDY

To study the importance of giving an angiotensin-converting enzyme (AC E) inhibitor to patients with reduced systolic function after an infar ction, the Trandodolapril Cardiac Evaluation study was designed to inc lude the majority of patients with echocardiographic signs of left ven tricular dysfunction among consecutively screened patients with infarc tions. A total of 2606 consecutive patients with left ventricular syst olic dysfunction corresponding to an ejection fraction less than or eq ual to 35% were identified. Of these patients, 1749 (67%) were randoml y assigned to receive oral trandolapril or placebo beginning on day 3 to 7 after the infarction. The follow-up period was 2 to 4 years. Tran dolapril reduced all-cause mortality, with a relative risk reduction a ssociated with trandolapril treatment of 0.78 (p = 0.0013). Benefit wa s seen within 1 month of treatment. Trandolapril also reduced cardiova scular death (relative risk 0.75, p = 0.001), sudden death (relative r isk 0.76, p = 0.03), and progression to severe/resistant heart failure (relative risk 0.71, p = 0.003). Recurrent myocardial infarction (fat al or nonfatal) was not significantly reduced (relative risk 0.86, p = 0.29). More than 80% of patients in both treatment groups reached the target dose of 4 mg trandolapril or placebo at the end of dose titrat ion. Nearly half of the patients in both treatment groups discontinued taking study medication before death or trial closure. The need for o pen-label ACE inhibition was the reason for discontinuation for 48 and 75 patients in the trandolapril and placebo groups, respectively. In conclusion, long-term treatment with trandolapril in patients with red uced left ventricular function shortly after myocardial infarction sig nificantly reduced mortality and morbidity. Most patients received the target dose of 4 mg trandolapril daily. The benefit observed is likel y to reflect the benefit in clinical practice because the majority of eligible patients were randomized and the difference patients leaving the trial to receive open-label ACE inhibition was moderate.