Effects of advancing age on the efficacy and side effects of antiarrhythmic drugs in post-myocardial infarction patients with ventricular arrhythmias. The CAST Investigators.

OBJECTIVE

To determine the effect of age on the response to anti-arrhythmic drugs.

DESIGN

Randomized controlled trial comparing particular drugs.

SETTING

Multi-institutional (The Cardiac Arrhythmia Suppression Trial, CAST).

PARTICIPANTS

2,371 patients, age less than 80, with ventricular arrhythmias after a recent myocardial infarction. Subjects classified by age as less than or equal to 55, 56-65, and 66-79 years.

INTERVENTION

Upwardly titrated doses of encainide, flecainide or moricizine. After identification of a tolerated and effective dose of one of the drugs, participants were randomized to that drug and dose versus its placebo for up to 10 months.

MAIN OUTCOME MEASURES

Efficacy of drug (suppression of ventricular premature depolarizations and/or non-sustained ventricular tachycardia), side effects and mortality.

RESULTS

Older patients had more previous MIs, congestive heart failure (CHF), hypertension, NSVT, repolarization abnormalities, digitalis use, and diuretic use. They had less pathologic Q-waves or electrocardiographic injury pattern, and their left ventricular ejection fraction (LVEF) was lower. First dose VPD suppression with the first drug averaged 53% and is not associated with age (P = 0.29). Adverse events including death are more frequent in older patients taking study drugs (P less than 0.001). This trend is consistent in all three study drugs and at varying LVEFs. History of prior MI, low LVEF, VPD (in log scale), and digitalis therapy also correlates with adverse events (all P less than 0.05). Following adjustment for these factors, older age is an independent predictor of adverse events (relative risk 1.30 per decade of age, P less than 0.001).

CONCLUSIONS

Older age increases the susceptibility to adverse cardiac events from a class of relatively toxic antiarrhythmic agents.