Angiotensin-converting enzyme inhibition after acute myocardial infarction with special reference to the Fourth International Study of Infarct Survival (ISIS-4)

Abstract

Role of ACE inhibitors in the management of asymptomatic or symptomatic left ventricular (LV) dysfunction after acute myocardial infarction (AMI) is well established. More recently, large clinical trials have evaluated the use of angiotensin-converting enzyme (ACE) inhibitors early after AMI, ie, within 24 hours of symptom onset. This concept has emerged with the understanding of pathophysiological changes occurring after AMI. Neurohormonal activation and ventricular remodelling after AMI form the basis of these changes, whereas the extent of LV dysfunction remains strongly predictive of poor outcome. The large clinical trials with mortality end point have shown modest benefit with early use of ACE inhibitors in an unselected population. However, the generalized use of ACE inhibitors remains controversial because of an overall small benefit. We review the pathophysiological changes occurring after AMI, the rationale for early use of ACE inhibitors, and the data available from the large clinical trials. We recommend consideration of early ACE inhibitor in all but the lowest risk patients. Clinical features of such a low-risk population would include small and nonanterior infarctions in patients less than 65 years of age and with LV ejection fractions greater than 50%. Objective assessment of LV function is warranted during hospitalization for AMI to appropriately select patients for ACE inhibitor therapy. Dosing should be started carefully to avoid hypotension and should be titrated to the goal of doses used in the large trials. Duration of therapy in patients at high risk for death or ventricular enlargement should be indefinite. Further large-scale secondary prevention trials with long-term treatment are underway to assess the effect of ACE inhibition on coronary disease progression and reinfarction.