Effects on ventricular arrhythmias of oral captopril and of oral mononitrate started early in acute myocardial infarction: results of a randomised placebo controlled trial.

Abstract

Objective-To assess the effects of oral vasodilator treatment on ventricular arrhythmias in acute myocardial infarction.Setting-Coronary care units at the John Radcliffe Hospital, Oxford, and the Royal Infirmary, Edinburgh.Patients-100 patients with suspected acute myocardial infarction entered the study at a mean of 13 hours from symptom onset.Design of Intervention-Double blind randomisation to 4 weeks' treatment with captopril (12.5 mg three times a day after a 6-25 mg test dose (n = 32)) or isosorbide mononitrate (20 mg three times a day (n = 31)) or placebo control (n = 37).Outcome measures-Ventricular arrhythmic events assessed by 48 hours of Holter monitoring starting at the time of randomisation.Results-The number of ventricular extrasystoles/hour for captopril, mononitrate, and placebo was respectively (median and range) 6 (0-162), 4 (0-38), and 10 (0-932) (2p < 0-02 mononitrate v placebo). The number of episodes of multiple extrasystoles/hour was 0-2 (0-22), 0-3 (0-4), and 0-5 (0-19); (2p < 0-02 mononitrate v placebo). Episodes of ventricular tachycardia showed a non-significant decrease in the captopril and mononitrate groups (mean (SEM) 3'2 (0.8), 2-4 (0.7), and 4*7 (1.3) for the 48 hour period). The incidence of idioventricular rhythm was also reduced in both active treatment groups (28%, 190/o, and 46% (2p < 0-05Conclusions-Oral mononitrate (and perhaps also captopril) seems to reduce the incidence of ventricular arrhythmias in the early phase of acute myocardial infarction. The effects on life-threatening arrhythmias, such as ventricular fibrillation, and on death can only be assessed in a much larger trial. (Br HeartJ7 1993;69:161-165) The renin-angiotensin system is activated during the first few days after acute myocardial infarction, ' 2 leading to stimulation of the heart and to increased systemic and coronary vascular resistance.3 Increases in systemic vascular resistance may increase myocardial wall stress, predisposing to infarct expansion, aneurysm, or progressive ventricular dilatation during the recovery phase after infarction.4 5 Moreover, both in experimental models and in clinical studies, increases in wall stress have been shown to increase the frequency of ventricular arrhythmias, whereas a reduction in wall stress has the opposite effect.6 7 Studies of patients in whom treatment with angiotensin converting enzyme inhibitors8 '°and nitrates" was started after acute myocardial infarction indicate that these agents can reduce systemic vascular resistance in acute myocardial infarction with favourable effects on the remodelling process. Intravenous glyceryl trinitrate can also reduce ventricular arrhythmias after acute myocardial infarction,'2 13 and similar observations have been made with angiotensin converting enzyme inhibitors among patients with congestive heart failure.'4 There have, however, been no controlled studies of the effects of oral nitrates or of angiotensin converting enzyme inhibitors on arrhythmias in acute myocardial infarction. In the present study, the...