Arrhythmias and Conduction Disturbances
Comparison of sotalol versus quinidine for maintenance of normal sinus rhythm in patients with chronic atrial fibrillation

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Abstract

Many clinicians choose sotalol for the prevention of recurrences of atrial fibrillation (AF) as an alternative to quinidine, which has been associated with an increase in long-term mortality. Using meta-analytic techniques, we compared the effects on maintenance of sinus rhythm and mortality of combined groups of patients with chronic AF treated with sotalol, quinidine, or a control drug. Rates of conversion at 6 months and mortality were combined for each group after performing sensitivity analysis to test for homogeneity. Bayesian estimates and corresponding 95% credibility intervals were constructed to compare the probabilities of achieving sinus rhythm and mortality among groups. A literature search revealed 4 sotalol studies, 6 quinidine studies, and 5 control studies that met inclusion criteria established a priori. The point estimates for maintaining normal sinus rhythm (at 6 months) and corresponding credibility intervals for the 3 groups were sotalol 50% (range 42% to 58%), quinidine 53% (range 48% to 59%), and control 32% (range 26% to 39%). When combining and comparing mortality effects, the following studies met the same inclusion criteria: 4 sotalol studies, 9 quinidine studies, and 7 control studies. The point estimates and corresponding credibility intervals for mortality in the 3 groups were sotalol 2.2% (range 0.6% to 4.8%), quinidine 3.0% (range 1.7% to 4.7%), and control 1.1% (range 0.3% to 2.4%). Sotalol and quinidine are comparable in their ability to maintain sinus rhythm at 6 months (about 50%) and both agents are superior to control. There is a trend for both agents to increase mortality with long-term therapy. These data do not support choosing sotalol over quinidine as a safer alternative for preventing recurrences of chronic AF.

Section snippets

Methods

A literature search was performed of the MEDLINE databases of the National Library of Medicine. From 1985 to the present, the search term “sotalol” was crossed with “atrial fibrillation” and “atrial flutter”; results of this search were crossed with the broad search strategy “clinical trial.” A similar search was performed from 1990 to the present using the search term “quinidine” These data were combined with data extracted from the previous meta-analysis1 to form a comprehensive collection of

Results

The literature search identified 19 quinidine-related studies and 14 sotalol-related studies. Of these, 10 sotalol and 10 quinidine studies were excluded for various reasons: study subjects were not being treated for chronic AF or were being treated for paroxysmal AF (6 studies), data were not available for predetermined time points (9 studies), subjects were being treated for postoperative AF (6 studies), inappropriate drug form was used (IV quinidine, nonracemic sotalol) (3 studies), and the

Discussion

Since the early 1900s, quinidine has been considered the drug of first choice for maintaining SR. However, the visible and influential publication of the Coplen et al meta-analysis after the CAST trial17 further questioned the long-term safety of antiarrhythmic drugs. In the analysis of Coplen et al, randomized, controlled trials investigating the efficacy and safety of quinidine in AF were combined. Quinidine was more effective than control (53% vs 32% remaining in normal SR at 6 months), but

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