Author + information
- Jalal K. Ghali, MD∗ ()
- ↵∗Department of Internal Medicine, Division of Cardiology, Mercer University School of Medicine, 707 Pine Street, Macon, Georgia 31201
Ruwald et al. (1) performed a non–pre-specified subgroup analysis of patients enrolled in MADIT-CRT (Multicenter Automatic Defibrillator Implantation Trial with Cardiac Resynchronization Therapy) who received either carvedilol or metoprolol. They concluded that carvedilol was associated with a 30% reduction in hospitalization for heart failure or death when compared to metoprolol (1). However, they have not emphasized the following:
1. The presence of significant differences in baseline characteristics that heavily favor carvedilol. In the metoprolol group and compared to the carvedilol group there were more men (79% vs. 71%) (2), patients were older (65 vs. 63.5 years of age) (3), and patients had higher prevalences of ischemic etiology (65% vs. 47%) (4) and prior myocardial infarction (53% vs. 37%), with a higher burden of ischemia as evident by higher prevalences of coronary artery bypass (34% vs. 25%) as well as non-coronary artery bypass revascularization (32% vs. 24%). Moreover, they had significantly more hospitalization in the prior year (53% vs. 43%) (5). In addition, they had a significantly higher prevalence of systolic blood pressure >140 mm Hg (21% vs. 16%). All of these factors combined could have heavily influenced the outcomes in favor of carvedilol.
2. The authors stated that 12% of those on metoprolol used the metoprolol tartrate preparation. Considering the absence of data from randomized trials documenting improvement in survival or reduction of hospitalization with metoprolol tartrate (6), these patients should have been excluded from analysis.
3. The causes of switching from carvedilol to metoprolol need to be ascertained. Was it because of low blood pressure? Was there clustering of events in these patients? Regardless, patients (n = 92) who were changed from 1 type to the other should have been excluded. It is virtually impossible to place them in either group with certainty.
In addition, comparing the low dose of beta-blockers in the MADIT-CRT to that in either OPTIMIZE-HF (Organized Program to Initiate Lifesaving Treatment in Hospitalized Patients with Heart Failure) or COPERNICUS (Carvedilol Prospective Randomized Cumulative Survival) is somewhat inappropriate as the dose of beta-blockers is expected to be lower in hospitalized patients and in patients with advanced heart failure.
Finally, would the authors care to speculate on a potential mechanism for the suggested synergistic effect of carvedilol in patients with left bundle branch block?
Please note: Dr. Ghali has in the past contributed to subgroup analysis involving patients from MERIT-HF. He has received an honorarium for giving a lecture on beta-blockers from AstraZenca.
- American College of Cardiology Foundation
- Ruwald M.H.,
- Ruwald A.C.,
- Jons C.,
- et al.
- Ghali J.K.,
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