Early treatment of acute myocardlal infarction with anglotensin-convertlng enzyme inhibition: Safety considerations

Early administration of ACE inhibitors may constitute a safe form of therapy for patients with AMI, particularly when the event is complicated by clinical signs or evidence of ventricular dysfunction.

Abstract

The use of angiotensin-converting enzyme (ACE) inhibitors in acute myocardial infarction (AMI) is based on their capacity to limit ventricular enlargement and dysfunction. To date, the safety profile of administration of ACE inhibitors early in the course of AMI has not been established. In-hospital and long-term consequences of treatment with the ACE inhibitor zofenopril initiated within 24 hours of the onset of symptoms were compared with those of standard treatment in an open-label trial involving 204 patients with AMI who were not undergoing thrombolytic treatment. Zofenopril promptly blocked ACE activation. Blockade was almost complete (91 +/- 6%) after 72 hours and paralleled decreases in systolic blood pressure. Systemic blood pressure was acutely reduced by zofenopril, and severe but reversible hypotension occurred in 15% of hospitalized patients and in 3% of those treated over the long term. No adverse clinical or biochemical events were reported during the course of zofenopril therapy. Overall cardiovascular mortality was not significantly reduced by early zofenopril compared with placebo therapy (7.8% vs 10.7% [difference not significant]). The inhospital incidence of acute left ventricular failure and ventricular arrhythmias decreased by 63% and 39%, respectively, among zofenopril-treated patients, who also reported fewer anginal episodes both acutely (68% reduction) and over the long term (56% reduction) and did not require as much drug treatment (i.e., diuretics, digoxin, and/or anti-ischemic agents) during the follow-up phase. Left ventricular size decreased and ejection fraction (EF) increased in patients who received zofenopril, and the improvement was greater among patients with poorer ventricular function (EF less than 40%). Early administration of ACE inhibitors may therefore constitute a safe form of therapy for patients with AMI, particularly when the event is complicated by clinical signs or evidence of ventricular dysfunction.