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Effects of Advancing Age on the Efficacy and Side Effects of Antiarrhythmic Drugs in Post‐Myocardial Infarction Patients with Ventricular Arrhythmias
Author(s) -
Akiyama Toshio,
Pawitan Yudi,
Campbell W. Barton,
Papa Louis,
Barker Allan H.,
Rubbert Pat,
Friedman Lawrence,
Keller Marcia,
Josephson Richard A.
Publication year - 1992
Publication title -
journal of the american geriatrics society
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.992
H-Index - 232
eISSN - 1532-5415
pISSN - 0002-8614
DOI - 10.1111/j.1532-5415.1992.tb01957.x
Subject(s) - medicine , ejection fraction , cardiology , myocardial infarction , ventricular tachycardia , digitalis , flecainide , adverse effect , heart failure , placebo , proarrhythmia , randomized controlled trial , atrial fibrillation , alternative medicine , pathology
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 <80, with ventricular arrhythmias after a recent myocardial infarction. Subjects classified by age as ≤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 < 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 < 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 < 0.001). Conclusions Older age increases the susceptibility to adverse cardiac events from a class of relatively toxic antiarrhythmic agents.