Atrial fibrillation: paroxysmal or persistent: many drugs can help conversion to sinus rhythm

Clinical bottom line (level 1a)

  1. Patients with paroxysmal or persistent atrial fibrillation who receive the following anti-arrhythmic drugs compared with placebo are more likely to revert to sinus rhythm within 24 hours (in order of efficacy):
    • ibutelide/dofetilide
    • flecainide
    • pilsicainide
    • pimenol
    • amiodarone
    • propafenone
    • quinidine
  2. The following drugs are not clearly better than control:
    • disopyramide
    • magnesium
    • sotalol
    • timolol
    • digoxin
Miller et al: Journal of Family Practice 2000; 49 : 1033-1046
McNamara et al: AHRQ Evidence Report 2001; 12 : -
Expires November 2003

The study

Systematic review of all randomised controlled trials of
  • Patients: paroxsymal or persistent (lasting > 48 hours and not terminating spontaneously) atrial fibrillation
  • Intervention: anti-arrhythmics: quinidine, procainamide, disopyramide, flecainide, propafenone, amiodarone, sotalol, ibutilide/dofetilide, beta-blockers, calcium-channel blockers (verapamil, diltiazem), digoxin compared with placebo, verapamil, dilatiazem, digoxin
  • Outcome: acute pharmacological conversion to sinus rhythm

    Articles found in all languages - though only English ones were included using CENTRAL (consisting of Medline, Embase and hand-searching of 100 journals), 1948 to May 1998 (search terms: detailed in text ) and searching Pubmed for related articles, Cardiovascular Randomized Controlled Trial Registery. Reference lists of relevant meta-analyses, recent review articles and major clinical trials were searched. Investigators in the field and search co-ordinators of relevant Cochrane Review groups were contacted to identify unpublished studies. Abstracts of major cardiology conference meetings for 1997-1998 were also checked and recent contents of journals frequently cited in the search results database.

    Selection criteria: selected by 3 clinicians
    Appraisal criteria: detailed in text - included study population, bias, confounding, outcomes, follow-up, statistical quality: by 2 independent reviewers
    Articles excluded if:
    • article did not address management of AF or atrial flutter
    • no human data
    • included post-operative AF data that could not be separated out
    • adults not part of study population
    • no original data in study
    • no randomisation
    • unable to separate out AF or flutter from other arrhythmias


    36 studies found comparing anti-arrhythmic agents and placebo (25 addressing conversion to sinus rhythm with follow-up ~ 24 hours, and 15 addressing maintenance of sinus rhythm with follow-up of 1-15 months); and 16 studies comparing 2 anti-arrhythmic agents
    Where studies were found to be heterogeneous, pooled estimates were derived using a random-effects model (propafenone v. control; amiodarone v. control)

    The evidence

    acute conversion of AF
    Outcome Time to outcome CER OR
    (95% CI)    		 NNT
    (95% CI)
    ibutilide/dofetilide v. control 24 hours /
    (30%)    		 29.1
    (9.8 to 86.1)     		2
    (1 to 2)
    flecainide v. control 24 hours /
    (30%)    		 24.7
    (9.0 to 68.3)     		2
    (1 to 2)
    pilsicainide v. control 24 hours /
    (30%)    		 8.7
    (2.3 to 33.2)     		2
    (2 to 5)
    pimenol v. control 24 hours /
    (30%)    		 8.5
    (1.9 to 38.8)     		2
    (2 to 7)
    amiodarone v. control 24 hours /
    (30%)    		 5.7
    (1.0 to 33.4)     		2
    (2 to infinity)
    propafenone v. control 24 hours /
    (30%)    		 4.6
    (2.6 to 8.2)     		3
    (2 to 4)
    quinidine v. control 24 hours /
    (30%)    		 2.9
    (1.2 to 7.0)     		4
    (2 to 25)
    disopyramide v. control 24 hours /
    (30%)    		 7.0
    (0.3 to 153)     		2
    (NNT = 1.5 to infinity;
    NNH = 5 to infinity)
    magnesium v. control 24 hours /
    (30%)    		 0.6
    (0.1 to 2.8)     		-10
    (NNT = 4 to infinity;
    NNH = 4 to infinity)
    sotalol v. control 24 hours /
    (30%)    		 0.4
    (0.0 to 3.0)     		-7
    (NNT = 4 to infinity;
    NNH = 3 to infinity)
    timolol v. control 24 hours /
    (30%)    		 3.1
    (0.6 to 17.6)     		4
    (NNT = 2 to infinity;
    NNH = 10 to infinity)
    digoxin v. placebo 24 hours /
    (30%)    		 1.3
    (0.8 to 2)     		17
    (NNT = 6 to infinity;
    NNH = 22 to infinity)
    class IA v. control 24 hours /
    (30%)    		 3.2
    (1.4 to 7.3)     		4
    (2 to 13)
    class IC v. control 24 hours /
    (30%)    		 6.2
    (3.5 to 10.8)     		2
    (2 to 3)

    • Propafenone given iv was not clearly better than oral at achieving cardioversion.

    Comments

    1. 12 non-English language articles were found, but full articles were not retrieved or combined in the meta-analysis. The evidence was strongest and comparable for quinidine, disopyramide, flecainide, propafenone, and sotalol.
    2. Most studies were small (< 100 patients), and study populations and antiarrhythmic administration varied greatly.
    3. 11 studies included patients with atrial flutter
    4. No study comparing propafenone with control was found.
    5. A conversion rate of 30% was assumed for the control group (ranged from 11% to 78% in studies, depending on whether patients with paroxysmal AF were included).

    Citation

    1. Miller MR, McNamara RL, Segal JB, et al: efficacy of agents for pharmacological conversion of atrial fibrillation and subsequent maintenance of sinus rhythm: a meta-analysis of clinical trials. Journal of Family Practice 2000; 49 : 1033-1046
    2. McNamara RL, Bass EB, Miller MR, et al: Management of New Onset Atrial Fibrillation. Evidence Report/Technology Assessment No. 12 (prepared by the Johns Hopkins University Evidence-based Practice Center in Baltimore, MD, under Contract No. 290-97-0006). AHRQ Publication Number 01-E026. Rockville, MD: Agency for Healthcare Research and Quality.. AHRQ Evidence Report 2001; 12 : -
    Search Terms: from AHRQ website
    Contributor: Chris Ball, November 2001
    Reviewer:

    Clinical Question.
    Patient atrial fibrillation
    Intervention or Exposure anti-arrhythmic
    Comparison control
    Outcome conversion to sinus rhythm within 24 hours