CARDIOVASCULAR MEDICINE

Meta-analysis of randomised controlled trials of the effectiveness of antiarrhythmic agents at promoting sinus rhythm in patients with atrial fibrillation

G Nichol¹, F McAlister², B Pham³, A Laupacis⁴, B Shea⁵, M Green⁶, A Tang⁶, G Wells⁷

¹ Clinical Epidemiology Program, Ottawa Health Research Institute, Ottawa Hospital, Ottawa, Ontario, Canada
² Division of General Internal Medicine, Department of Medicine, University of Alberta, Edmonton, Alberta, Canada
³ Glaxo Wellcome Inc, Mississauga, Ontario, Canada
⁴ Institute of Clinical Evaluative Sciences in Ontario, Toronto, Ontario, Canada
⁵ Institute of Population Health, Ottawa, Ontario, Canada
⁶ University of Ottawa Heart Institute, Ottawa, Ontario, Canada
⁷ Department of Epidemiology and Community Medicine, University of Ottawa, Ottawa, Ontario, Canada

Correspondence to:
Correspondence to:
Dr Graham Nichol, F6, Ottawa Hospital, Civic Site, 1053 Carling Avenue, Ottawa, Ontario, Canada K1Y 4E9;
grahamnichol{at}earthlink.net

Objective: To conduct a meta-analysis of randomised controlled trials to estimate the effectiveness of antiarrhythmic drugs at promoting sinus rhythm in patients with atrial fibrillation.

Design: Articles were identified by using a comprehensive search of English language papers indexed in Medline from 1966 to August 2001. For the outcomes of sinus rhythm and death, a random effects model was used to model repeated assessments within a study at different time points.

Setting: Emergency departments and ambulatory clinics.

Patients: Patients with atrial fibrillation.

Interventions: Antiarrhythmic agents grouped according to their Vaughan-Williams class.

Main outcome measures: Sinus rhythm and mortality.

Results: 91 articles met a priori criteria for inclusion in the analysis. Median duration of follow up was one day (range 0.04–1096, mean (SD) 46 (136) days). The median proportion of patients in sinus rhythm at follow up was 55% (range 0–100%) and 32% (range 0–90%) receiving active treatment and placebo, respectively. Median survival was 99% (range 55–100%) and 99% (range 55–100%). Compared with placebo, the following drug classes were associated with increased sinus rhythm at follow up: IA (treatment difference 21.5%, 95% confidence interval (CI) 16.3% to 26.8%); IC (treatment difference 33.1%, 95% CI 23.3% to 42.9%); and III (treatment difference 17.4%, 95% CI 11.5% to 23.3%). Class IC drugs were associated with increased sinus rhythm at follow up compared with class IV drugs (treatment difference 43.2%, 95% CI 11.5% to 75.0%). There was no significant difference in mortality between any drug classes.

Conclusions: Class IA, IC, and III drugs are associated with increased sinus rhythm at follow up compared with placebo. It is unclear whether any antiarrhythmic drug class is associated with increased or decreased mortality.

Keywords: antiarrhythmic agents; atrial fibrillation; meta-analysis

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