Meta-analysis: Quinidine reduces recurrences of atrial fibrillation after cardioversion but is associated with increased mortality
ACP J Club. 1991 Jan-Feb;114:17. doi:10.7326/ACPJC-1991-114-1-017
Coplen SE, Antman EM, Berlin JA, Hewitt P, Chalmers TC. Efficacy and safety of quinidine therapy for maintenance of sinus rhythm after cardioversion. A meta-analysis of randomized control trials. Circulation Oct. 1990;82:1106-16.
To evaluate the efficacy and safety of quinidine for the suppression of atrial fibrillation after cardioversion, through an analysis of randomized control trials in which the patients were followed for 3 to 12 months.
Citations from 1966 to July 1989 were retrieved from MEDLINE, using key words quinidine and latrial fibrillation or atrial flutter, combined with a broad strategy for obtaining clinical trials.
On blinded review, 2 independent readers agreed to the choice of 6 studies (of 52 on the topic) that met the following criteria: patients had chronic atrial fibrillation (lasting > 72 h), had cardioversion, and were randomized to quinidine or control groups; follow-up of patients allowed evaluation of efficacy at a minimum of 3 months; digoxin was the only other antiarrhythmic agent allowed.
Standardized forms were completed independently by 2 reviewers.
The 6 trials included 808 patients, aged 15 to 79 years. Duration of atrial fibrillation was ≤ 10 years. 52% of the patients had underlying valvular disease. Dosage and preparation of quinidine and use of placebos varied among the trials. 727 patients (90%) were followed for at least 3 months. 3 months after cardioversion, 69% of the patients receiving quinidine and 45% of the controls were in sinus rhythm, giving a pooled rate difference of 24% in favor of quinidine (95% CI 17% to 31%, P < 0.001). The rate differences at 6 months (23%) and 12 months (24%) also favored quinidine (P < 0.001) for both compared with the control group. The proportion of patients remaining in sinus rhythm steadily decreased to 50% of patients taking quinidine and 25% of control patients at 12 months. Of 373 patients receiving quinidine, 66 (18%) had side effects that included diarrhea, syncope, and pyrexia. 12 patients (2.9%) receiving quinidine died (3 from sudden cardiac death) compared with 3 patients (0.8%) assigned to the control groups. The odds of dying for patients receiving quinidine were about 3 times that for the control patients (P < 0.05).
Quinidine reduces recurrences of atrial fibrillation after cardioversion but is associated with a threefold increase in mortality.
Sources of funding: Department of Health and Human Services and the National Heart, Lung, and Blood Institute.
Address for article reprint: Dr. E. M. Antman, Cardiovascular Division, Brigham and Women's Hospital, 75 Francis Street, Boston, MA 02115, USA.
The authors of this well-researched and well-written article have drawn our attention to the benefits and adverse effects of an accepted treatment for a common cardiac arrhythmia, atrial fibrillation. This is timely considering that doubts have recently been cast on the safety of some other antiarrhythmic agents. The methods the authors have used are appropriate. Although they acknowledge some limitations of meta-analysis, they have highlighted the importance of such analyses in the absence of clinical trials that are large enough to detect an important but uncommon effect such as mortality. Clinicians should be very cautious about using quinidine: It reduces the recurrence of atrial fibrillation but increases the risk for death.
K. K. Teo, MD, PhD
University of AlbertaEdmonton, Alberta, Canada