Antiarrhythmics for maintaining sinus rhythm after reversing 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 embolism, 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 frequently recurs. A variety of drugs have been employed to avoid recurrences and keep the normal heart rhythm. This systematic review looked at the effectiveness and safety of antiarrhythmic drugs used to prevent recurrences of atrial fibrillation. This is an update of a review previously published in 2008 and 2012, with results of a search in January 2014 incorporated.

We found 59 studies testing various antiarrhythmic drugs and involving 21,305 patients. The risk of bias of the studies was low to moderate. The cumulative data from these studies showed that several drugs are effective at preventing recurrences of atrial fibrillation (quinidine, disopyramide, flecainide, propafenone, amiodarone, azimilide, dofetilide, dronedarone and sotalol) but all of them increased adverse effects. The data also showed that some of these drugs, one specific group called class IA drugs comprising quinidine, disopyramide and sotalol, may cause a small increase in the number of deaths in treated patients. Less data were available on the risk of embolic stroke (only 11 studies) and no consistent evidence of an effect on this outcome was apparent; one single study showed a reduction with dronedarone but that was not confirmed in other trials on the same drug. Finally, too few studies reported data on heart failure and the use of anticoagulants to be able to analyse the findings.

Thus, it is unclear if the long-term benefits obtained with antiarrhythmic drugs outweigh their risks.

Authors' conclusions: 

Several class IA, IC and III drugs, as well as class II drugs (beta-blockers), are moderately effective in maintaining sinus rhythm after conversion of atrial fibrillation. However, they increase adverse events, including pro-arrhythmia, and some of them (disopyramide, quinidine and sotalol) may increase mortality. Possible benefits on clinically relevant outcomes (stroke, embolism, heart failure) remain to be established.

Read the full abstract...
Background: 

Atrial fibrillation is the most frequent sustained arrhythmia. Atrial fibrillation frequently recurs after restoration of normal sinus rhythm. Antiarrhythmic drugs have been widely used to prevent recurrence, but the effect of these drugs on mortality and other clinical outcomes is unclear. This is an update of a review previously published in 2008 and 2012.

Objectives: 

To determine in patients who have recovered sinus rhythm after having atrial fibrillation, the effects of long-term treatment with antiarrhythmic drugs on death, stroke, embolism, drug adverse effects and recurrence of atrial fibrillation.

Search strategy: 

We updated the searches of CENTRAL in The Cochrane Library (2013, Issue 12 of 12), MEDLINE (to January 2014) and EMBASE (to January 2014). The reference lists of retrieved articles, recent reviews and meta-analyses were checked.

Selection criteria: 

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

Data collection and analysis: 

Two authors independently assessed quality and extracted data. Studies were pooled, if appropriate, using Peto odds ratio (OR). All results were calculated at one year of follow-up.

Main results: 

In this update three new studies, with 534 patients, were included making a total of 59 included studies comprising 21,305 patients. All included studies were randomised controlled trials. Allocation concealment was adequate in 17 trials, it was unclear in the remaining 42 trials. Risk of bias was assessed in all domains only in the trials included in this update.

Compared with controls, class IA drugs quinidine and disopyramide (OR 2.39, 95% confidence interval (95% CI) 1.03 to 5.59, number needed to treat to harm (NNTH) 109, 95% CI 34 to 4985) and sotalol (OR 2.23, 95% CI 1.1 to 4.50, NNTH 169, 95% CI 60 to 2068) were associated with increased all-cause mortality. Other antiarrhythmics did not seem to modify mortality, but our data could be underpowered to detect mild increases in mortality for several of the drugs studied.

Several class IA (disopyramide, quinidine), IC (flecainide, propafenone) and III (amiodarone, dofetilide, dronedarone, sotalol) drugs significantly reduced recurrence of atrial fibrillation (OR 0.19 to 0.70, number needed to treat to beneft (NNTB) 3 to 16). Beta-blockers (metoprolol) also significantly reduced atrial fibrillation recurrences (OR 0.62, 95% CI 0.44 to 0.88, NNTB 9).

All analysed drugs increased withdrawals due to adverse affects and all but amiodarone, dronedarone and propafenone increased pro-arrhythmia. Only 11 trials reported data on stroke. None of them found any significant difference with the exception of a single trial than found less strokes in the group treated with dronedarone compared to placebo. This finding was not confirmed in others studies on dronedarone.

We could not analyse heart failure and use of anticoagulation because few original studies reported on these measures.

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