Correspondence
Trandolapril in Patients with Left Ventricular Dysfunction after Myocardial Infarction
N Engl J Med 1996; 334:1546June 6, 1996
- Article
To the Editor:
The Trandolapril Cardiac Evaluation (TRACE) study (Dec. 21 issue),1 a multicenter study of patients with left ventricular systolic dysfunction after myocardial infarction, showed a clear benefit of long-term treatment with trandolapril, an angiotensin-converting–enzyme (ACE) inhibitor. In selected patients (wall-motion index, <1.2; ejection fraction, <35 percent), overall mortality was reduced by 22 percent and mortality from cardiovascular causes by 25 percent.
Often underused,2 beta-blockers have a benefit similar to that of trandolapril, with similar reductions in mortality in patients with myocardial infarction,3 and they are of even more benefit in the subgroups with left ventricular dysfunction.4,5 Thus, neurohumoral blockade by one of these drugs represents an important concept in the management of this condition. Indeed, further prospective randomized studies comparing ACE-inhibitor therapy with ACE-inhibitor therapy plus beta-blockers are needed to clarify whether neurohumoral blockade with combined treatment can further improve the clinical outcomes of patients with left ventricular dysfunction after infarction.
Some information about this question is provided in a subgroup analysis in Table 2 of the TRACE study. The greatest reduction in the risk of death associated with trandolapril therapy (relative risk, 0.60, vs. 0.78 overall) was achieved in the subgroup of patients taking beta-blockers at randomization. We would like to know whether beta-blocker treatment was continued and why there was no discussion of and explanation for the striking reduction in risk in this subgroup.
5 ReferencesG. Neumayr, M.D.
J. Gänzer, M.D.
University of Innsbruck, A-6020 Innsbruck, Austria1
Kober L ,Torp-Pedersen C ,Carlsen JE , et al. A clinical trial of the angiotensin-converting-enzyme inhibitor trandolapril in patients with left ventricular dysfunction after myocardial infarction. N Engl J Med 1995;333:1670-1676
Full Text | Web of Science | Medline2
Brand DA ,Newcomer LN ,Freiburger A ,Tian H . Cardiologists' practices compared with practice guidelines: use of beta-blockade after acute myocardial infarction. J Am Coll Cardiol 1995;26:1432-1436
CrossRef | Web of Science | Medline3
Yusuf S ,Wittes J ,Friedman L . Overview of results of randomized clinical trials in heart disease. I. Treatments following myocardial infarction. JAMA 1988;260:2088-2093
CrossRef | Web of Science | Medline4
The MIAMI Trial Research Group
Web of Science | Medline5
Furberg CD ,Hawkins CM ,Lichstein E . Effect of propranolol in postinfarction patients with mechanical or electrical complications. Circulation 1984;69:761-765
CrossRef | Web of Science | Medline
Author/Editor Response
The authors reply:
To the Editor: We agree with Drs. Neumayr and Gänzer that the result in the subgroup of patients who were taking a beta-blocker at the time of randomization is remarkable. We also agree that further prospective studies with beta-blockers are warranted. Data have been collected on medication throughout the trial. Detailed data on whether or how long this treatment was continued are currently not available, but in most cases the treatment was continued.
We did not emphasize the results in this subgroup because the number of patients receiving beta-blockers was small (16 percent of the total), they were not randomly assigned to the treatment, and there was no significant difference between this group of patients and those not receiving a beta-blocker. Subgroup analyses such as this can only generate hypotheses to be tested in the future.
Lars Køber, M.D.
Christian Torp-Pedersen, M.D., D.Sc.
Jan Carlsen, M.D.
Gentofte University Hospital, DK 2900 Hellerup, Denmark
