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Sex Differences in the Relationship Between Amiodarone Use and the Need for Permanent Pacing in Patients With Atrial Fibrillation
Vidal Essebag, MD, PhD;
Matthew R. Reynolds, MD, MSc;
Tom Hadjis, MD, MS;
Robert Lemery, MD;
Brian Olshansky, MD;
Alfred E. Buxton, MD;
Mark E. Josephson, MD;
Peter Zimetbaum, MD
Arch Intern Med. 2007;167(15):1648-1653.
Background Amiodarone use was associated with an increased need for pacemaker insertion in a retrospective study of patients with atrial fibrillation (AF) and prior myocardial infarction. The aims of this study were to determine prospectively whether amiodarone increases the need for pacemakers in a general population of patients with AF and whether this effect is modified by sex.
Methods The study included 1005 patients with new-onset AF who were enrolled in the Fibrillation Registry Assessing Costs, Therapies, Adverse events, and Lifestyle (FRACTAL). Multivariable Cox regression models, including time-dependent covariates accounting for medication exposure, were used to evaluate the risk of pacemaker insertion associated with amiodarone use.
Results Amiodarone use was associated with an increased risk of pacemaker insertion (hazard ratio [HR], 2.01; 95% confidence interval [CI], 1.08-3.76) after adjustment for age, sex, atrial flutter, coronary artery disease, heart failure, and hypertension. The effect of amiodarone use was modified by sex, with a significant risk in women but not in men (HR, 4.69; 95% CI, 1.99-11.05 vs HR, 1.05; 95% CI, 0.42-2.58 [P = .02]). This interaction remained significant after adjustment for weight, body mass index, weight-adjusted amiodarone dose, and use of other antiarrhythmic or rate control drugs.
Conclusion The risk of bradyarrhythmia requiring pacemaker insertion associated with amiodarone use for AF is significantly greater in women than in men, independent of weight or body mass index.
Author Affiliations: Divisions of Cardiology, McGill University Health Center, Montreal, Quebec, Canada (Drs Essebag and Hadjis), Beth Israel Deaconess Medical Center, Boston, Massachusetts (Drs Reynolds, Josephson, and Zimetbaum), University of Ottawa Heart Institute, Ottawa, Ontario, Canada (Dr Lemery), University of Iowa Hospitals, Iowa City (Dr Olshansky), and Rhode Island Hospital, Providence (Dr Buxton).
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