Effects of losartan and captopril on mortality and morbidity in high-risk patients after acute myocardial infarction: the OPTIMAAL randomised trial. Optimal Trial in Myocardial Infarction with Angiotensin II Antagonist Losartan

Abstract

Background: ACE inhibitors attenuate the detrimental effects of angiotensin II, and improve survival and reduce morbidity in patients with acute myocardial infarction and evidence of heart failure or left-ventricular dysfunction. Selective antagonism of the angiotensin type 1 receptor represents an alternative approach to inhibition of the renin-angiotensin system. We did a multicentre, randomised trial to test the hypothesis that the angiotensin II antagonist losartan would be superior or non-inferior to the ACE inhibitor captopril in decreasing all-cause mortality in high-risk patients after acute myocardial infarction.

Methods: 5477 patients 50 years of age or older (mean age 67.4 years [SD 9.8]), with confirmed acute myocardial infarction and heart failure during the acute phase or a new Q-wave anterior infarction or reinfarction, were recruited from 329 centres in seven European countries. Patients were randomly assigned and titrated to a target dose of losartan (50 mg once daily) or captopril (50 mg three times daily) as tolerated. The primary endpoint was all-cause mortality. Analysis was by intention to treat.

Findings: There were 946 deaths during a mean follow-up of 2.7 (0.9) years: 499 (18%) in the losartan group and 447 (16%) in the captopril group (relative risk 1.13 [95% CI 0.99-1.28], p=0.07). The results for the secondary and tertiary endpoints were as follows: sudden cardiac death or resuscitated cardiac arrest 239 (9%) versus 203 (7%), 1.19 (0.98-1.43), p=0.07, and fatal or non-fatal reinfarction 384 (14%) versus 379 (14%), 1.03 (0.89-1.18), p=0.72. The all-cause hospital admission rates were 1806 (66%) versus 1774 (65%), 1.03 (0.97-1.10), p=0.37. Losartan was significantly better tolerated than captopril, with fewer patients discontinuing study medication (458 [17%] vs 624 [23%], 0.70 [0.62-0.79], p<0.0001).

Interpretation: Since we saw a non-significant difference in total mortality in favour of captopril, ACE inhibitors should remain first-choice treatment in patients after complicated acute myocardial infarction. Losartan cannot be generally recommended in this population. However, it was better tolerated than captopril, and was associated with significantly fewer discontinuations. Although the role of losartan in patients intolerant of ACE inhibition is not clearly defined, it can be considered in such patients.