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Moricizine increased short-term mortality in survivors of myocardial infarction with low ejection fractions and ventricular premature depolarizations

ACP J Club. 1992 Nov-Dec;117:75. doi:10.7326/ACPJC-1992-117-3-075

Source Citation

The Cardiac Arrhythmia Suppression Trial II Investigators. Effect of the antiarrhythmic agent moricizine on survival after myocardial infarction. N Engl J Med. 1992 Jul 23;327:227-33



To determine whether moricizine reduces the risk for death or nonfatal cardiac arrest in survivors of myocardial infarction with asymptomatic or mildly symptomatic ventricular premature depolarizations and low ejection fractions.


2 linked, randomized, multicenter trials.


Hospitals and university-affiliated medical centers throughout North America and Sweden.


Patients averaged ≥ 6 ventricular premature depolarizations per hour on ambulatory electrocardiographic recordings within 90 days of myocardial infarction and had reduced ejection fractions (≥ 30 seconds at a rate of ≥ 120 complexes per minute were excluded. 1325 patients were included in a 14-day study to evaluate the risk of starting moricizine (Study 1), and 1374 patients whose arrhythmias were adequately (n = 1155) or partially (n = 219) suppressed by moricizine were included in a long-term study (average follow-up, 18 mo) to evaluate overall survival (Study 2).


In Study 1, patients received 600 mg of moricizine per day (200 mg every 8 h) or no treatment. In Study 2, patients received placebo or moricizine (either 600, 750, or 900 mg/d in 3 divided doses, as required to obtain adequate suppression of ventricular premature depolarizations).

Main outcome measures

In Study 1 the primary end point was death or nonfatal cardiac arrest from any cause within the 2-week period. In Study 2 the primary end point was death or nonfatal cardiac arrest caused by arrhythmia.

Main results

Both trials were stopped early when patients taking moricizine in Study 1 had an excess 2-week mortality compared with patients on no treatment (17 deaths or cardiac arrests [2.6%] vs 3 deaths [0.5%], P < 0.02). {This absolute risk increase of 2.1% means that 1 additional death or cardiac arrest occurred for every 48 patients who received moricizine (compared with no treatment), 95% CI 27 to 113; the relative risk increase was 462%, CI 77% to 1691%.}* At the same time, 49 suppressed and 10 partially suppressed patients on moricizine in Study 2 had died or suffered cardiac arrest caused by arrhythmia, compared with 42 and 9 patients, respectively on placebo (P > 0.2). It was estimated that the likelihood of observing a statistically significant benefit from moricizine within the planned duration of Study 2 was only 8%.


Moricizine increased short-term mortality in patients who survived a myocardial infarction with low ejection fractions and asymptomatic or mildly symptomatic ventricular premature depolarizations.

Source of funding: National Heart, Lung, and Blood Institute.

For article reprint: CAST Coordinating Center, 1107 N.E. 45th Street, Room 505, Seattle, WA 98105, USA.

*Numbers calculated from data in article.


This well-presented study confirms data accumulating on the dangers of treating asymptomatic or minimally symptomatic ventricular premature depolarization in patients after myocardial infarction. In applying these results in clinical practice, it is important to note that CAST-II, reported here, has made protocol changes from CAST-I (1) that raise the average patient risk (patients with less severe reductions of left ventricular ejection fraction were excluded; higher drug doses were permitted; patients could only be enrolled within 90 days of their infarction; and admission was opened to patients with sustained asymptomatic ventricular tachycardia). Nonetheless—and mirroring CAST-I—the result was increased mortality, this time with moricizine.

We continue to be disturbed by this high-risk group of postinfarction patients with depressed ejection fractions and ventricular tachycardia because, although their events are rare (1.5% and 6.6% combining drug and placebo groups), they often are fatal. Because arrhythmia suppression alone has not proved beneficial, physicians must avoid empiric antiarrhythmic therapy and consider individualizing patient investigation and management on the basis of additional risk-stratifying strategies, that is, signal-averaged electrocardiogram, electrophysiology studies, and longer hospital monitoring with drug therapy.

These results cannot be extrapolated to symptomatic arrhythmias or postinfarction polymorphic ventricular tachycardia, which may indicate recurrent ischemia or infarction requiring revascularization (2). Certainly, more work is needed in this area, and the results of this study point to the need for close evaluation and avoidance of empiric antiarrhythmic therapy.

Olivia V. Adair, MD
University of Colorado Health Sciences CenterDenver, Colorado, USA

Olivia V. Adair, MD
University of Colorado Health Sciences Center
Denver, Colorado, USA


1. The Cardiac Arrhythmia Suppression Trial (CAST) Investigators. N Engl J Med. 1989;321:406-12.

2. Wolfe CL, Nibley C, Bhandari A, Chatterjee J, Scheinman M. Circulation. 1991;84:1543-51.