Paris, France - The use of antiarrhythmic drugs is moderately effective in maintaining normal sinus rhythm after cardioversion of atrial fibrillation (AF), but nearly all drugs increase the risk of adverse side effects [1]. These are findings from a new review of the effect of treatment with antiarrhythmic drug therapy, with investigators concluding that the final risk/benefit ratio of long-term drug treatment remains unclear.

"The main findings are that several drugs of classes IA, IC, and III effectively maintain sinus rhythm, but all of them increase adverse effects, some potentially severe," Dr Carmelo Lafuente-Lafuente (Hôpital Lariboisière, Paris, France) told heartwire. "A final benefit on clinically relevant outcomes with these drugs remains unclear, as clinical outcomes have not been assessed in most of the trials. The risk of adverse effects should be balanced with the benefit expected for each individual patient."

In their review, Lafuente and colleagues report a trend toward an increase in the risk of death with the class IA drugs and suggest the drugs be used "most carefully." The results of the study are published in the April 11, 2006 issue of the Archives of Internal Medicine.

Explaining the rationale for the review, Lafuente said that there are many trials on antiarrhythmic drugs used for atrial fibrillation, but a comprehensive and objective synthesis of the results is still lacking. A risk for proarrhythmia and even for increased mortality with some drugs is well known, but a precise estimation of its magnitude during long-term treatment is not, she said.

In the meta-analysis, investigators included 44 trials with a total of 11 322 patients. Randomized controlled trials that compared antiarrhythmic drug therapy against a control (placebo or no treatment) or against another antiarrhythmic drug for more than six months were included in the analysis. Persistent AF was the most frequently studied type of AF, and only six studies included exclusively paroxysmal or recent-onset AF. The proportion of patients having underlying heart disease, defined by each study, ranged from 33% to 100%.

All class IA and IC drugs and all class III drugs, with the exception of dronedarone, significantly reduced the recurrence of AF. In treated patients, the recurrence rate at one year ranged from 42% to 67%. In a comparison of antiarrhythmic drugs, amiodarone reduced the recurrence of AF significantly more than combined class I drugs and more than sotalol.

Regarding adverse events, withdrawals were more frequent with antiarrhythmic drug therapy compared with controls, and nearly all drugs showed significantly increased proarrhythmic effects. Amiodarone and propafenone, however, did not increase the risk of proarrhythmia, and amiodarone was also associated with fewer withdrawals when compared with different drugs.

Overall, the mortality rate was low across the different studies, noted Lafuente. Compared with controls, a nonsignificant trend toward increased mortality was observed with quinidine. The increase in death became significant when investigators combined class IA drugs quinidine and disopyramide phosphate, resulting in a more than twofold increase in risk (OR 2.39, 95% CI 1.03-5.59). These results, however, were not reproduced when investigators analyzed only the PAFAC and SOPAT trials, two large, recent quinidine studies that did not report an increase in mortality. Amiodarone, when compared with class I drugs, showed a significant reduction in mortality (OR 0.39, 95% CI 0.19-0.79).

Lafuente told heartwire that the results are not particularly surprising, pointing out that the risks associated with the drugs have been known for some time. In the decision of rate vs rhythm control, this is another element in support of rate control, she said, although it is not conclusive, as the review was not a direct comparison between the two treatment strategies. While ablation might be another treatment alternative for these patients, its use is still very limited in clinical practice, added Lafuente, noting ablation is still relegated to younger patients with paroxysmal AF.

In selecting among the various antiarrhythmic drugs, Lafuente said that clinicians have to evaluate the characteristics of the patient, such as the existence of any type of cardiac disease, symptoms caused by the arrhythmia, the probability of maintaining sinus rhythm after cardioversion, and contraindications or risk factors for the different drugs, to choose the best strategy for each individual patient.