Patients with atrial fibrillation compared with those with sinus rhythm are at increased risk for thromboembolism, often mandating therapy directed at thromboembolism prevention. However, the safest, most efficacious strategy to prevent thromboembolism associated with atrial fibrillation is unknown. We developed a decision analysis to compare the risks and benefits of two common clinical strategies to prevent thromboembolism in the patient with atrial fibrillation: (1) sinus rhythm maintenance with quinidine sulfate or with amiodarone hydrochloride after cardioversion and (2) long-term anticoagulation with warfarin sodium.
A search was conducted of the Englishlanguage MEDLINE databases of the National Library of Medicine dated 1966 through December 1992. The search was conducted by intersecting "quinidine," "warfarin," or "amiodarone" with "atrial fibrillation." Six of 249 articles concerning quinidine and five of 20 articles concerning warfarin were judged by multiple reviewers to meet predetermined inclusion and exclusion criteria. To our knowledge, no randomized, placebo-controlled trials of amiodarone therapy for atrial fibrillation have been published. Five of 112 identified articles concerning amiodarone involved nonrandomized trials that met the remaining selection criteria and were included in this analysis.
Thromboembolic events and fatal nonthromboembolic adverse events during the course of therapy (defined as fatal proarrhythmia, fatal hemorrhage, and fatal noncardiac toxic effects) were considered to have equivalent weight. The total risk during therapy, defined as thromboembolic and fatal nonthromboembolic adverse events during the course of therapy, was evaluated over a range of baseline thromboembolism risks, from 1% to 20% per patient-year. Quinidine therapy compared with no therapy was associated with increased total risk, unless baseline thromboembolism risk exceeded 11% per patient-year. Total risk during warfarin therapy was less than total risk during quinidine therapy for the entire range of baseline thromboembolism risks, from 1% to 20% per patient-year. Total risk during warfarin or amiodarone therapy was similar and less than that with no therapy for the entire range of baseline risks.
Based on data from randomized, controlled trials of quinidine and warfarin, warfarin therapy appears to be the safest strategy for thromboembolism prevention in the patient with atrial fibrillation. The role of low-dose amiodarone therapy appears promising and warrants further study in randomized, controlled trials.(Arch Intern Med. 1995;155:913-920)