Correspondence
Implantable Defibrillators in Patients with Coronary Artery Disease at High Risk for Ventricular Arrhythmia
N Engl J Med 1997; 336:1676-1677June 5, 1997
- Article
To the Editor:
In their report on the Multicenter Automatic Defibrillator Implantation Trial (MADIT), Moss et al. (Dec. 26 issue)1 note the lower mortality in a group of patients receiving implantable defibrillators for unsustained ventricular tachycardia after myocardial infarction. However, the effect of the prophylactic use of defibrillators may have been confounded by other important differences between the two treatment groups. Beta-adrenergic antagonists are known to provide a benefit after myocardial infarction,2 and their more frequent use in the defibrillator group at the time of the last contact (27 percent, as compared with 5 percent in the conventional-therapy group) would be expected to reduce mortality in that group. In addition, a much larger proportion of patients in the conventional-therapy group received amiodarone (45 percent, as compared with 7 percent in the defibrillator group), raising the possibility of a proarrhythmic effect. Indeed, if defibrillators had been used in the control group in the Cardiac Arrhythmia Suppression Trial,3 the proarrhythmic effects of flecainide might not have been recognized or even contemplated.
The use of implantable defibrillators in patients with unsustained ventricular tachycardia and an ejection fraction of less than 35 percent after myocardial infarction has theoretical merit but substantial logistic and financial implications. When studies such as MADIT attempt to estimate the benefit of this strategy, it is critical that the use of adjunctive therapies not obscure the true worth of defibrillators.
3 ReferencesGerald J. Clesham, M.R.C.P.
Michael C. Petch, M.D.
Addenbrooke's Hospital, Cambridge CB2 2QQ, United Kingdom1
Moss AJ ,Hall WJ ,Cannom DS , et al. Improved survival with an implanted defibrillator in patients with coronary disease at high risk for ventricular arrhythmia. N Engl J Med 1996;335:1933-1940
Full Text | Web of Science | Medline2
The Norwegian Multicenter Study Group
Full Text | Web of Science | Medline3
The Cardiac Arrhythmia Suppression Trial (CAST) Investigators
Full Text | Web of Science | Medline
To the Editor:
The MADIT investigators should be lauded for their landmark study of the primary prevention of sudden death in a selected subgroup of patients after myocardial infarction. Since class I drugs and sotalol have been shown to increase mortality in studies of patients who have had myocardial infarctions, it is important to know the percentage of patients in the conventional-therapy group who were receiving these drugs at the time of death. It would also be of interest to know the percentage of patients with New York Heart Association (NYHA) class II heart failure and the percentage with class III heart failure and their respective mortality rates.
Barry F. Uretsky, M.D.
University of Texas Medical Branch at Galveston, Galveston, TX 77555-0270Author/Editor Response
The authors reply:
To the Editor: Drs. Clesham and Petch question whether the imbalance in beta-blocker use between the defibrillator and conventional-therapy groups contributed to the observed benefit of the defibrillators. At one month, beta-blockers were being used in 26 percent of the patients with defibrillators and in 8 percent of those receiving conventional treatment. With the use of the Cox proportional-hazards model, the unadjusted hazard ratio for the defibrillator group, as compared with the conventional-therapy group, was 0.46 (P =0.009), which is equivalent to a 54 percent reduction in mortality among the patients randomly assigned to the defibrillator group. The benefit in the defibrillator group remained statistically significant after the addition of beta-blocker use to the Cox model. Furthermore, the defibrillators were beneficial both in the patients receiving beta-blockers (hazard ratio, 0.51) and in those not receiving beta-blockers (hazard ratio, 0.27). Thus, the data do not support the speculation that the observed benefit of defibrillator therapy may have been due to greater beta-blocker use in the defibrillator group.
At one month, 74 percent of the conventionally treated patients were receiving amiodarone, as compared with 2 percent of the patients with defibrillators, and amiodarone may be considered a surrogate for conventional therapy. Several recent randomized trials have shown that amiodarone, as compared with placebo, has a neutral effect on mortality, with no evidence of proarrhythmia.1-3 On the basis of the results of these trials, it does not appear that amiodarone played an important part in the MADIT findings.
We appreciate the kind comments of Dr. Uretsky and his question about class I antiarrhythmic drugs. Of the 27 patients in the conventional-therapy group who died of cardiac causes, only 1 patient each was receiving procainamide, quinidine, and tocainide, and 3 were receiving mexiletine; of the 11 patients in the defibrillator group who died of cardiac causes, 1 was receiving disopyramide, and 2 were receiving mexiletine. None of the patients who died in either group received encainide, flecainide, moricizine, propafenone, or any other class I antiarrhythmic drug. With regard to the NYHA classification, 35 percent of the patients had class I disease, 48 percent had class II disease, and 17 percent had class III disease, with similar distributions in the two treatment groups. The reduction in mortality associated with defibrillator therapy was similar for the three NYHA classes, and there was no interaction between the NYHA class and defibrillator therapy.
We conclude that adjunctive therapies used in patients in MADIT did not detract from the benefit of implanted defibrillators in this high-risk population.
3 ReferencesArthur J. Moss, M.D.
W. Jackson Hall, Ph.D.
University of Rochester Medical Center, Rochester, NY 14642for the MADIT Investigators
1
Singh SN ,Fletcher RD ,Fisher SG , et al. Amiodarone in patients with congestive heart failure and asymptomatic ventricular arrhythmia. N Engl J Med 1995;333:77-82
Full Text | Web of Science | Medline2
Julian DG ,Camm AJ ,Frangin G , et al. Randomised trial of effect of amiodarone on mortality in patients with left-ventricular dysfunction after recent myocardial infarction: EMIAT. Lancet 1997;349:667-674
CrossRef | Web of Science | Medline3
Cairns JA ,Connolly SJ ,Roberts R ,Gent M . Randomised trial of outcome after myocardial infarction in patients with frequent or repetitive ventricular premature depolarisations: CAMIAT. Lancet 1997;349:675-682
CrossRef | Web of Science | Medline
