Correspondence
Prevention of Sudden Death in Patients with Coronary Artery Disease
N Engl J Med 2000; 342:1291-1292April 27, 2000
- Article
To the Editor:
Buxton et al. (Dec. 16 issue)1 report that electrophysiologically guided antiarrhythmic therapy, primarily with implantable defibrillators, but not antiarrhythmic drugs, reduces the risk of sudden death in high-risk patients with coronary disease. In Figure 1 of their article, however, the group with electrophysiologically guided therapy actually fared worse than the group with no antiarrhythmic therapy for a good part of the first year; it is only after the first year of enrollment that the two curves begin to diverge and the group receiving electrophysiologically guided therapy begins to show an advantage. No comment was made in the Discussion section about this finding.
Furthermore, it is unclear from the data presented how many of the patients in the group assigned to electrophysiologically guided therapy who did not receive a defibrillator ended up being treated with propafenone, one of the drugs mentioned in the initial study design2 and one we know is harmful to patients with coronary artery disease.3 Such treatment could have exaggerated the observed benefits among the patients in the group assigned to electrophysiologically guided therapy who received a defibrillator as compared with those assigned to electrophysiologically guided therapy who did not receive a defibrillator.
3 ReferencesAtul Aggarwal, M.D.
University of Vermont College of Medicine, Burlington, VT 054011
Buxton AE ,Lee KL ,Fisher JD ,Josephson ME ,Prystowsky EN ,Hafley G . A randomized study of the prevention of sudden death in patients with coronary artery disease. N Engl J Med 1999;341:1882-1890
Full Text | Web of Science | Medline2
Buxton AE ,Fisher JD ,Josephson ME , et al. Prevention of sudden death in patients with coronary artery disease: the Multicenter Tachycardia Trial (MUSTT). Prog Cardiovasc Dis 1993;36:215-226
CrossRef | Web of Science | Medline3
Echt DS ,Liebson PR ,Mitchell LB , et al. Mortality and morbidity in patients receiving encainide, flecainide, or placebo: the Cardiac Arrhythmia Suppression Trial. N Engl J Med 1991;324:781-788
Full Text | Web of Science | Medline
To the Editor:
In an otherwise excellent study, the authors state that it is unclear why antiarrhythmic-drug therapy guided by electrophysiologic testing does not improve survival as compared with no antiarrhythmic therapy. I suggest that it may be due to the fact that a significantly smaller percentage of patients assigned to electrophysiologically guided therapy were given pure beta-adrenergic antagonists (29 percent vs. 51 percent). Low-dose beta-adrenergic–antagonist therapy has become the appropriate form of therapy at my center, because it increases the left ventricular ejection fraction and decreases the number of ventricular ectopic beats.1 However, the authors were quite convincing regarding their primary conclusion — that implanted defibrillators reduce the risk of sudden death in high-risk patients with coronary artery disease.
1 ReferencesJeffrey M. Bloom, M.D.
Central Coast Primary Care, San Luis Obispo, CA 934011
Goldstein S ,Kennedy HL ,Hall C , et al. Metoprolol CR/XL in patients with heart failure: a pilot study examining the tolerability, safety, and effect on left ventricular ejection fraction. Am Heart J 1999;138:1158-1165
CrossRef | Web of Science | Medline
Author/Editor Response
The authors reply:
To the Editor: It is correct that survival among the patients randomly assigned to electrophysiologically guided therapy was initially no better than that among the patients randomly assigned to no antiarrhythmic therapy. This is accounted for by excess mortality during the first three months among the patients randomly assigned to electrophysiologically guided therapy without defibrillators, as depicted in Figure 3 and Figure 4 of our article. We suspect that this early decrease in survival may have been due to the proarrhythmic effects of pharmacologic antiarrhythmic therapy, but we cannot be certain about this.
At the beginning of this trial, there were no data to suggest that propafenone is harmful to patients with coronary artery disease, and in fact this is still the case. Propafenone was not studied in the Cardiac Arrhythmia Suppression Trial, the study referred to by Dr. Aggarwal. Furthermore, the use of propafenone was quite limited in our trial. Only 4 percent of the patients randomly assigned to electrophysiologically guided therapy were discharged receiving propafenone. Although the use of propafenone or other antiarrhythmic drugs could have exaggerated the observed benefits among the patients who received a defibrillator as compared with those who did not in the group given electrophysiologically guided therapy, such use would not have had any effect on the benefits of defibrillator therapy with respect to outcome among the patients randomly assigned to no antiarrhythmic therapy.
Dr. Bloom is correct that “pure” beta-adrenergic blocking agents were used less often in the patients randomly assigned to electrophysiologically guided therapy than in those assigned to no antiarrhythmic therapy. We believe that today most physicians would be less reluctant to use beta-adrenergic antagonists in patients such as those involved in our trial. The results of the study referred to by Dr. Bloom cannot be applied directly to the patients in our trial. That study involved patients with heart failure due to a variety of causes, a different population from that enrolled in the Multicenter Unsustained Tachycardia Trial. Furthermore, there has never been evidence that suppression of ventricular ectopic complexes decreases mortality.
Alfred E. Buxton, M.D.
Brown University School of Medicine, Providence, RI 02905Kerry L. Lee, Ph.D.
Duke University Clinical Research Institute, Durham, NC 27705
