TY - JOUR
T1 - Assessment of the efficacy and safety of antiarrhythmic therapy for chronic atrial fibrillation
T2 - Observations on the role of trial design and implications of drug-related mortality
AU - Reimold, Sharon C.
AU - Chalmers, Thomas C.
AU - Berlin, Jesse A.
AU - Antman, Elliott M.
N1 - Funding Information:
From the Cardiovascular Division, Department of Medicine, Women’s Hospital,a the Harvard School of Public Health,b sity of Pennsylvania, Clinical Epidemiology Unit.’ Supported by a National Research Service Award (T32-HL07604) from the National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Md. (Dr. Reimold) and by grants HS-05936 and HS-05523 from the Department of Health and Human Services. Received for publication Jan. 21, 1992; accepted April 24, 1992. Reprint requests: Elliott M. Antman, MD, Cardiovascular Division, and Women’s Hospital, 75 Francis St., Boston, MA 02115. 4lIf39874
PY - 1992/10
Y1 - 1992/10
N2 - The findings in clinical trials of antiarrhythmic drug efficacy and safety are frequently difficult to compare, since study design often has an important effect on trial outcome. To explore this problem further, we compared three designs-randomized control, nonrandomized control, and uncontrolled-collectively enrolling 2415 patients in 21 trials reporting on the role of quinidine in the prevention of chronic atrial fibrillation. The proportion of patients remaining in sinus rhythm at 3, 6, and 12 months after cardioversion was calculated by means of Kaplan-Meier techniques, and the data were pooled for each trial design. For the randomized control trials the difference in the absolute percentage of patients remaining in sinus rhythm in the quinidine and control groups was 24% at each of the three fellow-up intervals. Contrary to findings in the randomized control trials, the magnitude of the treatment benefit in nonrandomized trials was smaller and declined markedly over time. The percentage of patients remaining in sinus rhythm in the uncontrolled trials was intermediate to the percentages in the other two trial designs. When the data from all three trial designs were pooled, the crude mortality rate was 2.0% in quinidine-treated patients and 0.6% in control patients. Sudden cardiac death or ventricular fibrillation was the cause of death in 13 of 19 patients for whom the cause of death was known, highlighting the potential risk of quinidine-induced proarrhythmia. Although quinidine is effective in maintaining sinus rhythm, estimates of the treatment effect vary among trial types. Because antiarrhythmic therapy with quinidine for suppression of atrial fibrillation has not been shown to reduce the risk of mortality, the decision to institute therapy should be guided strongly by patient symptoms.
AB - The findings in clinical trials of antiarrhythmic drug efficacy and safety are frequently difficult to compare, since study design often has an important effect on trial outcome. To explore this problem further, we compared three designs-randomized control, nonrandomized control, and uncontrolled-collectively enrolling 2415 patients in 21 trials reporting on the role of quinidine in the prevention of chronic atrial fibrillation. The proportion of patients remaining in sinus rhythm at 3, 6, and 12 months after cardioversion was calculated by means of Kaplan-Meier techniques, and the data were pooled for each trial design. For the randomized control trials the difference in the absolute percentage of patients remaining in sinus rhythm in the quinidine and control groups was 24% at each of the three fellow-up intervals. Contrary to findings in the randomized control trials, the magnitude of the treatment benefit in nonrandomized trials was smaller and declined markedly over time. The percentage of patients remaining in sinus rhythm in the uncontrolled trials was intermediate to the percentages in the other two trial designs. When the data from all three trial designs were pooled, the crude mortality rate was 2.0% in quinidine-treated patients and 0.6% in control patients. Sudden cardiac death or ventricular fibrillation was the cause of death in 13 of 19 patients for whom the cause of death was known, highlighting the potential risk of quinidine-induced proarrhythmia. Although quinidine is effective in maintaining sinus rhythm, estimates of the treatment effect vary among trial types. Because antiarrhythmic therapy with quinidine for suppression of atrial fibrillation has not been shown to reduce the risk of mortality, the decision to institute therapy should be guided strongly by patient symptoms.
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U2 - 10.1016/0002-8703(92)90974-Z
DO - 10.1016/0002-8703(92)90974-Z
M3 - Article
C2 - 1388328
AN - SCOPUS:0026744534
SN - 0002-8703
VL - 124
SP - 924
EP - 932
JO - American heart journal
JF - American heart journal
IS - 4
ER -