ArticlesEffects of losartan and captopril on mortality and morbidity in high-risk patients after acute myocardial infarction: the OPTIMAAL randomised trial
Introduction
Patients with acute myocardial infarction and substantial myocardial injury frequently show clinical evidence of heart failure or left-ventricular dysfunction. Such patients have a high risk of morbidity and mortality. Angiotensin-converting-enzyme (ACE) inhibitors reduce morbidity and improve survival in chronic heart failure and after acute myocardial infarction, especially in selected, high-risk patients.1 Treatment attenuates infarct expansion,2 reduces reinfarction rate,3 reduces the incidence of subsequent heart failure,4 and is regarded as the treatment of choice in such patients.5
Blockade of the production of angiotensin II is incomplete during ACE inhibition:6 some conversion of angiotensin I continues, especially after low-dose and long-term treatment,7 and myocardial production of angiotensin II persists.8 As well as being caused by incomplete ACE inhibition, this continued generation of angiotensin II also results from non-ACE-dependent pathways.6 Angiotensin II production can be almost completely maintained in the myocardium despite effective suppression of circulating angiotensin II by ACE inhibition.8 An increased concentration of plasma angiotensin II despite ACE inhibitor treatment is associated with increased mortality.9 Antagonism of the effects of angiotensin II at the receptor level would therefore seem sensible, as would assessment of whether a selective angiotensin II antagonist could provide equal or better protection than an ACE inhibitor.
OPTIMAAL (Optimal Trial in Myocardial Infarction with the Angiotensin II Antagonist Losartan) was an investigator-initiated, multinational, double-blind, randomised, parallel-group study designed to compare the effects of the receptor antagonist losartan with those of the ACE inhibitor captopril on mortality and morbidity in patients with acute myocardial infarction and evidence of heart failure or left-ventricular dysfunction. Losartan is a highly specific, non-peptide antagonist of the type-1 angiotensin II receptor.10 Captopril was chosen as the ACE inhibitor because it has an established dose and efficacy in patients after complicated acute myocardial infarction compared with placebo.11
Section snippets
Patients
Patients of either sex with documented acute myocardial infarction and who were at least 50 years of age were eligible for screening. A description of the recruitment details, the total cohort at baseline, a comparison between countries, and the results of the screening process have been published.12
Baseline acute myocardial infarction was defined as fulfilling at least two of the following criteria: a history of typical chest pain for longer than 20 min, ST elevation on electrocardiograph, or
Results
5477 patients were randomised and all were included in the final analyses (figure 1). 946 deaths (all-cause mortality) were reported during the 14 866 patient-years of follow-up. Only one patient was lost to follow-up. Table 1 provides a comparison of baseline characteristics for the entire cohort and according to treatment group. The groups were closely matched and no important differences in the specified demographics were detected. Table 2 provides a comparison of major inclusion criteria
Discussion
The OPTIMAAL trial compared the treatment effect of losartan 50 mg once daily with captopril 50 mg three times daily on mortality and morbidity in patients with evidence of heart failure or left-ventricular dysfunction after acute myocardial infarction. This trial did not show superiority or non-inferiority of losartan relative to captopril. A non-significant difference in total mortality was seen in favour of captopril. The incidence of reinfarction, revascularisation, and all-cause hospital
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