Author + information
- Andrea Di Lenarda, MDa,
- Gastone Sabbadini, MDa,
- Dario Gregori, PhDa,
- Gianfranco Sinagra, MDa,
- On behalf of the Heart Muscle Disease Study Group
We are grateful for the opportunity to respond to the comments by Drs. Fauchier and Giraudeau concerning our recent article in the Journal(1). Specifically, they draw attention to the differences in the baseline arrhythmic profile of our patients with dilated cardiomyopathy who thereafter received carvedilol or metoprolol. We agree that the inhomogeneity in patient characteristics is surely an important issue, and, although in general terms, in our article, we have already commented on this point by admitting the existence of some differences in baseline characteristics between the carvedilol and metoprolol groups. With reference to the specific objection made by Drs. Fauchier and Giraudeau, we recognize that patients receiving carvedilol had a higher prevalence of both nonsustained ventricular tachycardia (NSVT) and ventricular couplets (VC), although these differences did not reach statistical significance (in all likelihood because of the small number of patients and the high variability). ⇓
Because a more severe arrhythmic picture at baseline might have contributed to the finding of a favorable effect of carvedilol on NSVT and VC, Drs. Fauchier and Giraudeau are correct when they claim more precise information on the variables used for adjustment in the comparison of the prevalence of ventricular arrhythmias. In short, we can specify that all differences were tested considering the baseline arrhythmic profile and concurrent amiodarone therapy as potentially confounding factors (Table 1). On the basis of this statistical approach, we believe that the potential impact of patient heterogeneity on our results has been limited, and, moreover, that the effects seen on ventricular arrhythmias are more likely due to beta-blocker therapy than to a phenomenon of regression toward the mean. A simple test (both parametric or nonparametric) would hardly be appropriate in comparing two groups with high heterogeneity in baseline characteristics.
Furthermore, to avoid a basic misunderstanding of the objective of our study, one specific point needs to be emphasized. The study was not designed to address the question of whether one beta-blocker is more effective than another, but rather (as clearly stated in our article) to evaluate whether carvedilol may provide additional benefits in a select subgroup of patients with dilated cardiomyopathy who were treated long term with metoprolol, as well as poor responders to metoprolol. Therefore, the lack of further benefits in patients randomized to continue taking metoprolol was, in some way, expected. However, from this evidence, we have not argued (or stated) that metoprolol is ineffective or less effective than carvedilol; rather, we have suggested that carvedilol treatment may be beneficial in patients showing unsatisfactory clinical responses to metoprolol treatment.
Finally, we agree with the comments made by Drs. Fauchier and Giraudeau regarding the U.S. Carvedilol Study (2) and the MERIT-HF trial (3), even though it cannot be denied that the data from the U.S. program, at least, imply a beneficial effect of carvedilol on sudden death. In any case, whatever the opinion on this issue, the truth is that the comparative efficacy of carvedilol and metoprolol in preventing sudden death will remain an open question until the conclusion of the ongoing COMET trial.
We thank Drs Fauchier and Giraudeau for having brought their pertinent criticisms to our attention.
- American College of Cardiology