When is Drug Therapy Warranted to Prevent Sudden Cardiac Death?

Abstract

Sudden arrhythmic death is an important contributor to the mortality rate in patients with cardiac disease, accounting for over 450,000 deaths per year in the USA alone. About 80% of such patients, particularly those survivors of acute myocardial infarction with low ventricular ejection fractions, have coronary artery disease. The remainder have cardiomyopathy or valvular disease and the common denominator in all these subsets of patients is the association with complex and frequent premature ventricular contractions (PVCs). The most common mechanism of death is ventricular tachycardia (VT) deteriorating into ventricular fibrillation (VF); the initiating factor is a PVC (the trigger mechanism). Thus, if an effective antiarrhythmic (? antifibrillatory) regimen could be identified, these subsets of patients clearly constitute targets for mortality reduction by pharmacological suppression. The question that has arisen is whether suppression of PVCs will reduce the incidence of sudden death (the PVC hypothesis). The alternative approach is to modify the arrhythmogenic substrate in the ventricle by eliminating the source of ischaemia, extirpating the ectopic focus, dividing re-entry circuits, or pharmacologically prolonging the refractory period so that VT does not deterioate into VF (the antifibrillatory approach). Whether sudden death in postinfarct survivors could be reduced has been the subject of study. These patients are at high risk of sudden death or reinfarction, the risk being greatest in those with a low ventricular ejection fraction, continuing myocardial ischaemia and asymptomatic high density and complex PVCs. Numerous trials have been performed to determine whether beta-blockers, calcium antagonists and antiarrhythmic agents reduce the incidence of sudden death and reinfarction in survivors of myocardial infarction. beta-Blockers remain the only agents which, when given prophylactically, have been found to reduce the incidence of sudden death and reinfarction (by 18 to 45% in the first 2 years after infarction). The reduced incidence of sudden death appears to be associated with a reduction in VF, but not in PVCs. A meta-analysis of data from trials with calcium antagonists found that these drugs either had no effect or tended to increase mortality (by an average of 6%), indicating that an effect on ischaemia alone is unlikely to be the sole mechanism mediating the effect of beta-blockers. The divergent effects of beta-blockers and calcium antagonists are unexplained, but may be partly due to a lack of a significant bradycardiac effect of calcium antagonists. There were no differences in effect between different calcium antagonists.(ABSTRACT TRUNCATED AT 400 WORDS)