Objectives:

Atrial fibrillation (AF) is the most common arrhythmia physicians face in clinical practice, with an incidence of up to 2.3 percent per year and a prevalence of almost 9 percent in those age 80--89 years. In addition to having various symptoms, patients with AF have increased risk for stroke and death. This report synthesizes the available evidence on strategies for handling each of the following key aspects in the management of patients with new onset AF: electrical cardioversion and pharmacological conversion, maintenance of sinus rhythm, ventricular rate control, stroke prevention, outpatient management, and echocardiography.

Search Strategy:

The primary sources for the literature search were the Cochrane Collaboration's database of controlled clinical trials (1948 to 1998) and MEDLINE (1966 to 1998). Specific search terms included atrial fibrillation and atrial flutter, both as medical subject headings and as text words.

Selection Criteria:

Articles were included in the evidence synthesis if they reported on original data from a randomized controlled trial addressing noninvasive management of non-post-operative atrial fibrillation in adults. Many of these trials included patients with atrial flutter.

Data Collection and Analysis:

A review of 521 potentially relevant citations yielded 179 articles that met eligibility criteria. Study quality was assessed and data abstracted by pairs of reviewers. Results are presented in evidence tables and, where deemed appropriate, synthesized by meta-analysis and decision analysis.

Main Results:

Questions regarding pharmacological conversion of AF, maintenance of sinus rhythm, pharmacological rate control, and antithrombotic therapy were addressed directly in the clinical trial literature.

For conversion of AF to sinus rhythm, 46 trials were identified that evaluated 18 different medications. Digoxin, verapamil, and diltiazem were found to be no better than placebo and were combined with placebo to form a control group. The bulk of the evidence for any individual agent existed in comparison with this control group, limiting direct agent-to-agent comparisons. The odds ratio (OR) and 95 percent confidence intervals (CI) for successful conversion of AF revealed the strongest evidence of efficacy, and largest treatment effect sizes, for flecainide (OR 24.7, CI 9.0 to 68) and ibutilide/dofetilide (OR 29.1, CI 9.8 to 86) when compared with control. Strong evidence of efficacy with a fairly large treatment effect size also existed for propafenone (OR 4.6, CI 2.6 to 8.2). Quinidine had moderate evidence of efficacy and a modest treatment effect size compared with control treatment (OR 2.9, CI 1.2 to 7.0). Disopyramide (OR 7.0, CI 0.3 to 152) and amiodarone (OR 5.7, CI 1.0 to 33.4) had suggestive evidence of efficacy, while sotalol (OR 0.4, CI 0.0 to 3.0) had suggestive evidence of negative efficacy for conversion. For maintenance of sinus rhythm, 29 trials were identified that evaluated 10 different medications. Strong evidence of efficacy with fairly large treatment effect sizes for maintenance of sinus rhythm, when compared with control treatment, existed for quinidine (OR 4.1, CI 2.5 to 6.7), disopyramide (OR 3.4, CI 1.6 to 7.1), flecainide (OR 3.1, CI 1.5 to 6.2), propafenone (OR 3.7, CI 2.4 to 5.7), and sotalol (OR 7.1, CI 3.8 to 13.4). There were no randomized clinical trials of amiodarone versus control treatment for maintenance of sinus rhythm. One trial provided moderate evidence of efficacy for amiodarone compared with disopyramide for maintenance of sinus rhythm.

For rate control, 45 trials were identified that evaluated 17 medications. The design and outcome measures of these trials were too disparate for meta-analysis. In general, the evidence suggested that calcium-channel blockers and some beta-blockers were effective for controlling heart rate during exercise.

For antithrombotic therapy, 11 trials were identified that evaluated four medications. The aggregate odds of having a stroke for a subject on warfarin compared with a subject on placebo were 0.30 (CI 0.19 to 0.48), indicating strong evidence of the efficacy of warfarin. However, the odds of having a major bleed were 1.90 (CI 0.89 to 4.04), indicating suggestive evidence for a higher bleeding rate for subjects taking warfarin. The evidence on the efficacy of aspirin compared with placebo was moderately strong for subjects without a prior history of stroke (OR 0.65, CI 0.43 to 0.99) but was inconclusive in subjects with a prior history of stroke. The odds of having a major bleed for subjects on aspirin were 0.81 (CI 0.37 to 1.77), indicating inconclusive evidence. The evidence from trials directly comparing warfarin and aspirin was inadequate to permit strong conclusions. The evidence was inconclusive for the use of low molecular weight heparin, induprofen, or a combination of low-dose warfarin and aspirin for stroke prevention.

In decision analysis, one attempt at electrical cardioversion with pharmacological maintenance therapy was estimated to be cost-effective compared with antithrombotic therapy alone for patients 55 years old and older, regardless of risk factors. For stroke prevention in patients at low risk of stroke (~1 percent/year), aspirin was the most cost-effective therapy. In patients with a high risk of stroke (~10 percent/year), warfarin was the most cost-effective strategy for stroke prevention. In those with an intermediate risk of stroke (~3-6 percent/year), the most cost-effective treatment depended on assumptions about the quality-of-life effects of taking warfarin. In patients without risk factors for thromboembolism, transesophageal echo-cardiography was the most cost-effective test for guiding decisions about antithrombotic therapy.

High priorities for additional research are 1) improving the understanding of the effects of treatment of AF on quality of life, 2) assessing the efficacy of amiodarone in randomized controlled clinical trials, 3) evaluating the risks and benefits of each antiarrhythmic medication in subjects with coronary artery disease, and especially the risk of ventricular arrhythmia, 4) directly comparing antithrombotic agents for prevention of stroke, particularly in low- and moderate-risk populations, and 5) determining the safety of outpatient initiation of antiarrhythmic therapy for AF. Many of these priorities and specifically the second one are beginning to be addressed in trials, such as the AFFIRM Study and the PIAF trial.

Conclusions:

Several medications were efficacious in conversion of AF and subsequent maintenance of sinus rhythm. Calcium-channel blockers and beta-blockers were more efficacious than digoxin in controlling ventricular rate during exercise in subjects with AF. Although subjects on warfarin had higher rates of bleeds, warfarin generally was more efficacious than aspirin in preventing stroke in subjects with AF. One attempt of electrical cardioversion with subsequent pharmacological maintenance is cost-effective compared with antithrombotic therapy alone.