Ninety-one RCTs (n=8,563) were included.
Effect of anti-arrhythmic agents on sinus rhythm.
Class IA, IC and III drugs were associated with significant increases in the proportion of patients in sinus rhythm compared with placebo. In addition, the class IC drugs were associated with a significant increase in the proportion of patients in sinus rhythm compared with class IV drugs.
Compared with placebo, the mean treatment difference was 21.5% (95% CI: 16.3, 26.8, p<0.0001) for class IA drugs (7 trials), 33.1% (95% CI: 23.3, 42.9, p<0.0001) for class IC (17 trials), 17.4% (95% CI: 11.5, 23.3, p=0.001) for class III (19 trials), and 13.1% (95% CI: -7.2, 33.3, p=0.15) for digoxin (4 trials).
The mean treatment difference was 4.1% (95% CI: -8.0, 16.2, p=0.42) for class IA versus class III drugs (6 trials), -3.4% (95% CI: 17.2, 10.5, p=0.6) for class IC versus class III (10 trials), 43.2% (95% CI: 11.5, 75.0, p=0.03) for class IC versus class IV (4 trials), and 15.2% (95% CI: -43.7, 74.2, p=0.19) for class III versus digoxin (2 trials). There appears to be an error in the result for class IC versus class III drugs since the mean treatment difference (-3.4%) lies outside the confidence range reported (95% CI: 17.2, 10.5).
Effect of anti-arrhythmic agents on mortality.
There was no significant difference in mortality between active treatment and placebo, or between active treatment and comparison drug, for any of the classes of anti-arrhythmic drugs considered.
Compared with placebo, the mean treatment difference was 0.96% (95% CI: -0.45, 2.36, p<0.14) for class IA drugs (5 trials), -0.08% (95% CI: -0.20, 0.04, p<0.16) for class IC (14 trials), -0.11% (95% CI: -0.32, 0.09, p=0.25) for class III (17 trials), and 0.02% (95% CI: -0.01, 0.06, p=0.12) for digoxin (4 trials).
The mean treatment difference was 0.17% (95% CI: -0.58, 0.92, p=0.53) for class IA versus class III drugs (5 trials), -0.26% (95% CI: -1.10, 0.59, p=0.50) for class IC versus class III (8 trials), -0.06% (95% CI: -2.26, 2.13, p=0.91) for class IC versus class IV (4 trials), and 0.48% (95% CI: -13.71, 14.67, p=0.74) for class III versus digoxin (2 trials).
The authors also reported the data for the individual class IA, IC and III drugs.
Sensitivity analyses.
In comparison with placebo, there was an association between anti- arrhythmic drugs and increased sinus rhythm among the trials of class IC and class III drugs that followed patients up for less than 7 days. There was also an association between anti-arrhythmic drugs and increased sinus rhythm, compared with placebo, among the trials of class IA and class III drugs. When the large trial was included in the analysis, the results remained non significant. Also, the results were not altered when the analysis was adjusted for study quality or study cohorts. The results relating to mortality were not altered for any of the sensitivity analyses.