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The Cochrane Database of Systematic... Oct 2007Atrial fibrillation (AF) is the most frequent sustained arrhythmia. After restoration of normal sinus rhythm, the recurrence rate of AF is high. Antiarrhythmic drugs... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
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.
OBJECTIVES
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 STRATEGY
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.
Topics: Anti-Arrhythmia Agents; Atrial Fibrillation; Electric Countershock; Humans; Randomized Controlled Trials as Topic; Secondary Prevention
PubMed: 17943835
DOI: 10.1002/14651858.CD005049.pub2 -
European Heart Journal Feb 2007To assess the efficacy and safety of adjunctive antiarrhythmic drug therapy for preventing implantable cardioverter defibrillator (ICD) therapies. (Review)
Review
AIMS
To assess the efficacy and safety of adjunctive antiarrhythmic drug therapy for preventing implantable cardioverter defibrillator (ICD) therapies.
METHODS AND RESULTS
We conducted a systematic literature search to identify all randomized, controlled trials assessing the efficacy of adjunctive antiarrhythmic drug therapy. Trial data were reviewed and extracted independently by two investigators in an unblinded, standardized manner. Eight trials including a total of 1889 patients were analysed. There was heterogeneity in the type of antiarrhythmic used in the treatment arm (amiodarone, sotalol, azimilide, and dofetilide) as well as in the control group (five trials compared with placebo and three trials compared with beta-blocker). The main outcome, risk of shock therapy, was reduced when comparing amiodarone plus beta-blocker with beta-blocker alone (HR 0.27; 95% CI 0.14-0.52) and when comparing sotalol with placebo (HR 0.55; 95% CI 0.4-0.78). The effect was not conclusive when comparing sotalol with other beta-blocker (HR 0.61; 95% CI 0.37-1) and azimilide or dofetilide with placebo (HR 0.78; 95% CI 0.58-1.04 and HR 0.67; 95% CI 0.43-1.04, respectively). Although there were some benefits for secondary outcomes in all antiarrhythmics, the magnitude of the benefit was higher with amiodarone.
CONCLUSION
Amiodarone is the most effective treatment to reduce ICD shock therapies. The benefit of other antiarrhythmics is limited to secondary outcomes.
Topics: Anti-Arrhythmia Agents; Arrhythmias, Cardiac; Chemotherapy, Adjuvant; Clinical Trials as Topic; Defibrillators, Implantable; Humans; Treatment Outcome
PubMed: 17227788
DOI: 10.1093/eurheartj/ehl478 -
Archives of Internal Medicine Apr 2006A variety of antiarrhythmic drugs have been used to prevent recurrence of atrial fibrillation after conversion to sinus rhythm. We performed a systematic review to... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
A variety of antiarrhythmic drugs have been used to prevent recurrence of atrial fibrillation after conversion to sinus rhythm. We performed a systematic review to determine the effect of long-term treatment with those drugs on death, embolisms, adverse effects, and atrial fibrillation recurrence.
METHODS
We searched MEDLINE, EMBASE, the Cochrane Library (all up to May 2005), and the reference lists of retrieved articles. We included randomized controlled trials that compared any antiarrhythmic against control (placebo or no treatment) or another antiarrhythmic, for more than 6 months. Postoperative atrial fibrillation was excluded. Two evaluators independently reviewed the retrieved studies and extracted all data. Disagreements were resolved by discussion. All results were calculated at 1 year of follow-up.
RESULTS
Forty-four trials were included, with a total of 11 322 patients. Several class IA (disopyramide phosphate, quinidine sulfate), class IC (flecainide acetate, propafenone hydrochloride), and class III (amiodarone, dofetilide, sotalol hydrochloride) drugs significantly reduced recurrence of atrial fibrillation (number needed to treat, 2-9), but all increased withdrawals due to adverse effects (number needed to harm [NNH], 9-27) and all but amiodarone and propafenone increased proarrhythmia (NNH, 17-119). Class IA drugs, pooled, were associated with increased mortality compared with controls (Peto odds ratio, 2.39; 95% confidence interval, 1.03-5.59; P = .04; NNH, 109). No other antiarrhythmic showed a significant effect on mortality compared with controls. We could not analyze other outcomes because data were lacking.
CONCLUSION
Class IA, IC, and III drugs are effective in maintaining sinus rhythm but increase adverse effects, and class IA drugs may increase mortality.
Topics: Anti-Arrhythmia Agents; Atrial Fibrillation; Electric Countershock; Humans; Randomized Controlled Trials as Topic; Secondary Prevention
PubMed: 16606807
DOI: 10.1001/archinte.166.7.719 -
Circulation Jul 2002Postoperative atrial fibrillation (AF) is a common complication of cardiac surgery and has been associated with increased incidence of other complications and increased... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Postoperative atrial fibrillation (AF) is a common complication of cardiac surgery and has been associated with increased incidence of other complications and increased hospital length of stay (LOS). Prevention of AF is a reasonable clinical goal, and, consequently, many randomized trials have evaluated the effectiveness of pharmacological and nonpharmacological interventions for prevention of AF. To better understand the role of various prophylactic therapies against postoperative AF, a systematic review of evidence from randomized trials was performed.
METHODS AND RESULTS
Fifty-two randomized trials (controlled by placebo or routine treatment) of beta-blockers, sotalol, amiodarone, or pacing were identified by systematic literature search. The 3 drug treatments each prevented AF with the following odds ratios (ORs): beta-blockers, 0.39 (95% CI, 0.28 to 0.52); sotalol, 0.35 (95% CI, 0.26 to 0.49); and amiodarone, 0.48 (95% CI, 0.37 to 0.61). Pacing was also effective; for biatrial pacing, the OR was 0.46 (95% CI, 0.30 to 0.71). The influence of pharmacological interventions on LOS was as follows: -0.66 day (95% CI, 2.04 to 0.72) for beta-blockers; -0.40 day (95% CI, 0.87 to 0.08) for sotalol; and -0.91 day (95% CI, 1.59 to -0.23) for amiodarone. The influence for biatrial pacing was -1.54 day (95% CI, -2.85 to -0.24). The incidence of stroke was 1.2% in all the treatment groups combined and 1.4% in controls (OR, 0.90; 95% CI, 0.46 to 1.74).
CONCLUSIONS
Beta-blockers, sotalol, and amiodarone all reduce risk of postoperative AF with no marked difference between them. There is evidence that use of these drugs will reduce LOS. Biatrial pacing is a promising new treatment opportunity. There was no evidence that reducing postoperative AF reduces stroke; however, data on stroke are incomplete.
Topics: Adrenergic beta-Antagonists; Amiodarone; Anti-Arrhythmia Agents; Atrial Fibrillation; Cardiac Pacing, Artificial; Cardiac Surgical Procedures; Humans; Length of Stay; Randomized Controlled Trials as Topic; Risk Factors; Sotalol; Stroke
PubMed: 12093773
DOI: 10.1161/01.cir.0000021113.44111.3e -
Progress in Cardiovascular Diseases 2001This report reviews the efficacy of currently available antiarrhythmic agents for conversion of atrial fibrilation (AF) to normal sinus rhythm (NSR). A systematic search... (Review)
Review
This report reviews the efficacy of currently available antiarrhythmic agents for conversion of atrial fibrilation (AF) to normal sinus rhythm (NSR). A systematic search of literature in the English language was done on computerized databases, such as MEDLINE, EMBASE, and Current Contents, in reference lists, by manual searching, and in contact with expert informants. Published studies involving humans that described the use of antiarrhythmic therapy for conversion of AF to NSR were considered and only studies that examined the use of agents currently available in the United States were included. Studies exclusively describing antiarrhythmic therapy for conversion of postsurgical AF were excluded. The methodology and results of each trial were assessed and attempts were made to acquire additional information from investigators when needed. Assessment of methodological quality was incorporated into a levels-of-evidence scheme. Eighty-eight trials were included, of which 34 (39%) included a placebo group (level I data). We found in recent-onset AF of less than 7 days, intravenous (i.v.) procainamide, high-dose i.v. or high-dose combination i.v. and oral amiodarone, oral quinidine, oral flecainide, oral propafenone, and high-dose oral amiodarone are more effective than placebo for converting AF to NSR. In recent-onset AF of less than 90 days, i.v. ibutilide is more effective than placebo and i.v. procainamide. In chronic AF, oral dofetilide converts AF to NSR within 72 hours, and oral propafenone and amiodarone are effective after 30 days of therapy. We conclude than for conversion of recent-onset AF of less than 7 days, procainamide may be considered a preferred i.v. agent and propafenone a preferred oral agent. For conversion of recent-onset AF of longer duration (less than 90 days), i.v. ibutilide may be considered a preferred agent. For patients with chronic AF and left ventricular dysfunction, direct current cardioversion is the preferred conversion method. Larger, well-designed randomized controlled trials with clinically important endpoints in specific populations of AF patients are needed.
Topics: Amiodarone; Anti-Arrhythmia Agents; Atrial Fibrillation; Flecainide; Humans; Phenethylamines; Procainamide; Propafenone; Quinidine; Sotalol; Sulfonamides
PubMed: 11568824
DOI: 10.1053/pcad.2001.26966