Review: Quinidine is associated with increased mortality in ventricular arrhythmias
ACP J Club. 1992 Mar-April;116:45. doi:10.7326/ACPJC-1992-116-2-045
Morganroth J, Goin JE. Quinidine-related mortality in the short-to-medium-term treatment of ventricular arrhythmias. A meta-analysis. Circulation. 1991 Nov;84: 1977-83.
To assess the effect of quinidine on mortality, compared with other class I antiarrhythmic agents (flecainide, mexiletine, tocainide, and propafenone), in patients with benign or potentially malignant ventricular arrhythmias in randomized controlled trials.
For this meta-analysis, data were taken from a MEDLINE computer search of the English literature through 1990, manual searches of references and review articles, and sources identified by experts. No unpublished data were included.
Studies were included in the main analysis if they used ambulatory electrocardiographic monitoring to determine the presence and frequency of ventricular arrhythmias during a placebo lead-in; used randomized, double-blind designs; and included an explicit report of all deaths occurring during the trial. 4 studies met these criteria. 6 crossover studies and 1 parallel study with no initial assessment of ventricular arrhythmias were excluded.
The 2 authors independently reviewed the publications for death and the exacerbation or provocation of ventricular arrhythmias (early proarrhythmic response).
Of a total of 1009 patients, 502 were treated with quinidine, 141 with flecainide, 246 with mexiletine, 67 with tocainide, and 53 with propafenone. Patient characteristics and efficacy criteria were similar in the 4 trials: The mean age ranged from 58 to 62 years; the proportion of men, from 68% to 82%, and the proportion with ischemic heart disease, from 44% to 77%. Quinidine was administered as quinidine sulfate in escalating doses for 2 weeks in 2 trials and for 12 weeks in 1, and in a fixed dose for 8 weeks in the other trial. Patients on quinidine were about 3 times as likely to die as patients on the other drugs. 12 of 502 patients (2.4%) died in the quinidine group compared with 4 of 502 patients (0.8%) in the groups treated with other class I antiarrhythmic agents (absolute risk increase 1.6%, 95% CI 0% to 3%, P = 0.05). There were 20 occurrences of early proarrhythmia with quinidine, and 11 with the other agents (P = 0.09). The results were homogeneous from trial to trial.
Short or medium-term use of quinidine is associated with increased mortality compared with the other class I antiarrhythmic agents, flecainide, mexiletine, tocainide, and propafenone, in patients with ventricular arrhythmias.
Source of funding: Not stated.
Address for article reprint: Dr. J. Morganroth, Graduate Hospital, One Graduate Plaza, Philadelphia, PA 19146, USA.
In this meta-analysis, Morganroth and Goin found that quinidine, compared with other class I antiarrhythmic agents, is associated with a nominally significant excess mortality and a trend toward excess proarrhythmia. The methods appear sound. Although it focused on quinidine, had restrictive inclusion criteria, and involved relatively few patients (n = 1009), its implications are important.
Quinidine was compared with agents that have been found to be harmful (flecainide) or potentially harmful or ineffective (mexiletine, tocainide, propafenone). The study's conclusions are consistent with those of other studies of antiarrhythmic agents, highlighted by the randomized Cardiac Arrythmia Suppression Trial that showed excess mortality with encainide and flecainide.
A large placebo-controlled trial with quinidine is not likely to be done, but I have gathered published data from small placebo-controlled trials that suggest that considerable excess harm would be demonstrated (1).
Because, according to these authors, quinidine is the most commonly prescribed antiarrhythmic agent (around 40%) in the United States, any excess harm from its use, however slight, will have important implications.
All these developments in antiarrhythmic therapy reinforce the need for continuing critical evaluation of both the indications for treating cardiac arrhythmias (considering both the type of patient and the type of arrhythmias) and attempts to prevent sudden death (2, 3); one should weigh carefully the harm/benefit ratio of an agent, no matter how familiar, each time any patient is treated.
Koon K. Teo, MB, PhD
University of AlbertaEdmonton, Alberta, Canada
Koon K. Teo, MB, PhD
University of Alberta
Edmonton, Alberta, Canada