Antiarrhythmics for maintaining sinus rhythm after cardioversion of atrial fibrillation

  • Review
  • Intervention




Atrial fibrillation (AF) is the most frequent sustained arrhythmia. After restoration of normal sinus rhythm, the recurrence rate of AF is high. Antiarrhythmic drugs have been widely used to prevent recurrence, but the effect of these drugs on mortality and other clinical outcomes is unclear.


To determine, in patients who recovered sinus rhythm after AF, the effect of long-term treatment with antiarrhythmic drugs on death, stroke and embolism, adverse effects, pro-arrhythmia and recurrence of AF. If several antiarrhythmics were effective our secondary aim was to compare them.

Search methods

The Cochrane Central Register of Controlled Trials (CENTRAL) on The Cochrane Libary (Issue 2, 2005), MEDLINE (1950 to May 2005) and EMBASE (1966 to May 2005) were searched. The reference lists of retrieved articles, recent reviews and meta-analyses were checked. No language restrictions were applied.

Selection criteria

Two independent reviewers selected randomised controlled trials comparing any antiarrhythmic with a control (no treatment, placebo or drugs for rate control) or with another antiarrhythmic, in adults who had AF and in whom sinus rhythm was restored. Post-operative AF was excluded.

Data collection and analysis

Two reviewers independently assessed quality and extracted data, on an intention-to-treat basis. Disagreements were resolved by discussion. Studies were pooled, if appropriate, using Peto odds ratio (OR).

Main results

45 studies met inclusion criteria, comprising 12,559 patients. All results were calculated at 1 year of follow-up. Class IA drugs (disopyramide, quinidine) were associated with increased mortality compared with controls (OR 2.39, 95% confidence interval (CI) 1.03 to 5.59, P = 0.04, number needed to harm (NNH) 109, 95% CI 34 to 4985). Other antiarrhythmics did not modify mortality.

Several class IA (disopyramide, quinidine), IC (flecainide, propafenone) and III (amiodarone, dofetilide, dronedarone, sotalol) drugs significantly reduced recurrence of AF (OR 0.19 to 0.60, number needed to treat 2 to 9), but all increased withdrawals due to adverse affects (NNH 17 to 36) and all but amiodarone and propafenone increased pro-arrhythmia (NNH 17 to 119).

Authors' conclusions

Several class IA, IC and III drugs are effective in maintaining sinus rhythm but increase adverse events, including pro-arrhythmia, and disopyramide and quinidine are associated with increased mortality. Any benefit on clinically relevant outcomes (embolisms, heart failure, mortality) remains to be established.

Plain language summary

Antiarrhythmics for maintaining sinus rhythm afrer cardioverision of atrial fibrillation

Atrial fibrillation is a disease where the heart rhythm is irregular (this is called arrhythmia) and too fast (this is called tachycardia, from the Greek "tachy" meaning fast). Atrial fibrillation may produce complications, either in the heart (heart failure, syncope) or in other organs (mainly causing embolisms, which is the formation of blood clots in the cavities of the heart that may then travel to other places, for example the brain).

Atrial fibrillation can be reverted, restoring normal heart rhythm, by using drugs or a controlled electrical shock. However, a major problem is that atrial fibrillation recurs frequently. A variety of drugs have been employed to avoid recurrences and keep normal heart rhythm. This systematic review looked at the effectiveness and safety of antiarrhythmic drugs used to prevent recurrences of atrial fibrillation.

We found 45 good quality studies testing various antiarrhythmic drugs, involving 12,559 patients. The cumulative data from these studies show that several drugs are effective at preventing recurrences of atrial fibrillation (quinidine, disopyramide, flecainide, propafenone, amiodarone, dofetilide, dronedarone and sotalol), but all of them increased adverse effects. The data shows also that one specific group of drugs (called "class IA", and comprising quinidine and disopyramide) may cause a small increase in the number of deaths in treated patients. A limitation of the review was that most of the studies did not assessed the complications associated with atrial fibrillation (heart failure, stroke, embolisms), so the effect of antiarrhythmic drugs on these endpoints is unknown.

It is unclear if the long-term benefits obtained with antiarrhythmic drugs outweighs their risks.