Draft Key Questions
Disposition of Comments Report
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Archived: This report is greater than 3 years old. Findings may be used for research purposes, but should not be considered current.
There are two generally accepted strategies for managing atrial fibrillation (AF): rate control and rhythm control. However, within each strategic approach there are a large number of potential pharmacological and nonpharmacological therapies, and the comparative safety and effectiveness of these therapies--both within and between strategies--are uncertain.
We searched PubMed®, Embase®, and the Cochrane Database of Systematic Reviews for relevant English-language comparative studies.
Two investigators screened each abstract and full-text article for inclusion, abstracted data, rated quality and applicability, and graded evidence. When possible, random-effects models were used to compute summary estimates of effects.
Our review included 182 articles (148 unique studies): 14 studies relevant to rate-control drugs, 3 relevant to strict versus lenient rate control, 6 relevant to rate-control procedures versus drugs in patients for whom initial pharmacotherapy was ineffective, 42 relevant to antiarrhythmic drugs and electrical cardioversion for conversion to sinus rhythm, 83 relevant to rhythm-control procedures and drugs for maintenance of sinus rhythm, and 14 focusing on the comparison of rate- and rhythm-control strategies. Our ability to draw conclusions for the Key Questions addressing rate-control strategies was limited by the small number of available studies that assessed comparable therapies and outcomes, although we found a high strength of evidence for consistent benefit of calcium channel blockers (verapamil or diltiazem) compared with digoxin for ventricular rate control. For comparisons of methods for electrical cardioversion for conversion to sinus rhythm, there was high strength of evidence that use of a single biphasic waveform was more effective than use of a single monophasic waveform (odds ratio [OR] 4.39; 95% confidence interval [CI], 2.84 to 6.78) and that a 200 Joules (J) biphasic shock was less effective than a 360 J monophasic shock (OR 0.16; 95% CI, 0.05 to 0.53). Drug enhancement of external electrical cardioversion demonstrated a benefit compared with no drug enhancement (moderate strength of evidence), but data evaluating whether any one antiarrhythmic agent was more effective than others at restoring sinus rhythm were inconclusive. Our review found high strength of evidence supporting pulmonary vein isolation (PVI) versus antiarrhythmic drugs for maintenance of sinus rhythm in a select subset of patients (those with paroxysmal AF who were younger and with no more than mild structural heart disease; OR 6.51; 95% CI, 3.22 to 13.16) and moderate strength of evidence for adding a surgical Maze procedure at the time of other cardiac surgery (specifically mitral valve surgery) as opposed to mitral valve surgery alone (OR 5.80; 95% CI, 1.79 to 18.81). Comparing rate- and rhythm-control strategies, there was moderate strength of evidence supporting comparable efficacy with regard to all-cause mortality (OR 1.34; 95% CI, 0.89 to 2.02); cardiovascular mortality (OR 0.96; 95% CI, 0.77 to 1.20); stroke (OR 0.99; 95% CI, 0.76 to 1.30); and bleeding events (OR 1.10; 95% CI, 0.87 to 1.38). Cardiovascular hospitalizations were lower with rate-control strategies than with rhythm-control strategies (OR 0.25; 95% CI, 0.14 to 0.43; high strength of evidence). We were unable to conclude whether treatment effects varied by patient characteristics due to the paucity of studies that focused on specific patient subgroups.
In assessing clinical outcomes associated with rate- versus rhythm-control strategies, our review of recent evidence agrees with prior reviews demonstrating little overall difference in outcomes between these two strategic approaches. Uncertainties still exist within specific subgroups of interest, among the wide variety of pharmacological and procedural therapies within each strategic approach, and in the impact of strategies on long-term clinical outcomes. Specifically, our review highlights the need for additional studies evaluating final outcomes such as mortality, stroke, and cardiovascular hospitalizations.