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Circulation, Vol 84, 1977-1983, Copyright © 1991 by American Heart Association
J Morganroth and JE Goin
BACKGROUND. The interim results of the Cardiac Arrhythmia Suppression Trial
requires physicians to use a higher threshold for employing antiarrhythmic
agents in the treatment of benign or potentially lethal ventricular
arrhythmias. Many have managed patients by switching to the traditional
class I quinidine despite its known proarrhythmic tendency. METHODS AND
RESULTS. To evaluate the relation between quinidine therapy and mortality
in patients with benign or potentially lethal ventricular arrhythmias, we
performed a meta-analysis on four randomized double- blind active
controlled parallel trials evaluating 1,009 patients in which quinidine (n
= 502) was compared to flecainide (n = 141), mexiletine (n = 246),
tocainide (n = 67), and propafenone (n = 53). All four trials had similar
patient selection, protocols, and methodology (e.g., placebo lead-in and
Holter monitoring) but varying lengths of drug exposure. A total of 12
deaths were reported on quinidine and four deaths on the other drugs: two
on mexiletine, one on flecainide, and one on tocainide. The statistical
analysis of the mortality rates was based on techniques for combining data
across separate strata. Based on maximum likelihood estimation, the
combined risk of dying on quinidine was statistically significantly higher
compared to the other four drugs with a risk difference of 1.6%. The 95%
confidence interval was 0-3.1% (p = 0.05). The likelihood ratio test for
uniformity of the risk difference across strata showed the trials to be
homogeneous (p = 0.88). There was one death recorded for the placebo
lead-in period (2 weeks' exposure for 624 patients and 1 week for 385
patients), and seven deaths were reported within 2 weeks on active drug
treatment--six on quinidine and one on mexiletine. Furthermore,
proarrhythmia was reported in 20 patients on quinidine versus 11 patients
on the four other drugs (p = 0.09). CONCLUSIONS. These data suggest that
quinidine may have an adverse effect on mortality as compared to other
class I antiarrhythmic agents and that individualized patient selection for
the use of this agent be carefully weighed relative to its potential for
harm and benefit.
ARTICLES
Quinidine-related mortality in the short-to-medium-term treatment of ventricular arrhythmias. A meta-analysis
Graduate Hospital, Philadelphia, PA 19146.
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