Atrial fibrillation: adverse effects on antiarrhythmic agents are common

Clinical bottom line (level 2a)

Patients with paroxysmal or persistent atrial fibrillation who take anti-arrhythmic drugs often have adverse effects severe enough to require withdrawal or dosage decrease.
Arrhythmias, particularly ventricular ones, are also common.

Segal et al: Journal of Family Practice 2000; 49 : 47-59
McNamara et al: AHRQ Evidence Report 2001; 12 : -

Expires November 2003

The study

Systematic review of all randomised controlled trials of

Patients: previous episodes of paroxsymal or persistent (lasting > 48 hours and not terminating spontaneously) atrial fibrillation

Intervention: anti-arrhythmic drug compared with another anti-arrhythmic agent or placebo

Outcome: adverse effects

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 Investigators in the field and search co-ordinators of relevant Cochrane Review groups were contacted to identify unpublished studies.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

The evidence

ventricular arrhythmias:
- quinidine: 0%-12%
- propafenone: 0%-3%
- flecainide: 0%-2%
- amiodarone: 0%-15%
- sotalol: 0%-1%
- ibutilide: 5%-9%
- dofetilide: 3%
- disopyramide, digoxin, verapamil, placebo: all 0%
other arrhythmias:
- quinidine: 0%-28%
- propafenone: 0%-17%
- flecainide: 0%-12%
- amiodarone: 0%-9%
- sotalol: 2%-44%
- ibutilide: 38%-39%
- placebo: 0%-9%
- verapamil: 0%-9%
- disopyramide, digoxin: both 0%
withdrawal or dosage decrease:
- quinidine: 0%-58%
- disopyramide: 0%-55%
- propafenone: 0%-55%
- flecainide: 0%-20%
- sotalol: 4%-44%
- digoxin: 25%-36%
- placebo: 0%-8%
- verapamil: 0%

Comments

Reporting of adverse effects or reasons for withdrawal was inconsistent.
8 non-English language articles were found, but full articles were not retrieved or combined in the meta-analysis.
Most studies were small (< 100 patients), and study populations, drug administration, and length of follow-up varied greatly.
11 studies included patients with atrial flutter

Citation

Segal JB, McNamara RL, Miller MR, et al: the evidence regarding the drugs used for ventricular rate control. Journal of Family Practice 2000; 49 : 47-59
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}	_{antiarrhythmic drug}
_Outcome	_{adverse effects}