Author + information
- Jean Rouleau, MD, FACC* ()
- ↵*Universite de Montreal, Medecine, C.P. 6128, Succursale Centre-Ville, Montreal QC H3C 3J7, Canada
In his letter, Dr. Ghali notes that one may expect patients with heart failure and the lowest systolic blood pressure, those at highest risk, to enjoy a higher relative benefit from the use of carvedilol. Indeed, in the COPERNICUS study (1), patients with the lowest systolic blood pressure were at highest risk. We did not, however, identify a greater relative benefit with carvedilol. Dr. Ghali invites us to speculate as to why a greater relative benefit was not found. At least four possibilities exist.
First, because patients with the lowest systolic blood pressure had the greatest rate of discontinuation of carvedilol, and less frequently achieved target dose, it is possible that, if one corrected for adherence and dose, these patients indeed did derive a greater relative benefit from carvedilol, when they could tolerate a target dose. Alternatively, as the relative benefit of bisoprolol (2) and controlled release metoprolol (3) in patients with somewhat less severe heart failure was found to be comparable to that of carvedilol in patients with more severe heart failure, it may be that the relative benefit of beta-blockers is independent of the severity of heart failure.
A third possibility is that a relatively greater direct benefit of carvedilol in patients with the lowest systolic blood pressure was masked by greater indirect risk associated with excessive hypotension due to the combined vasodilator and beta-blocking effects of carvedilol. Whatever the explanation, our study was not powered to find a difference in subgroups, such that a true beneficial interaction between systolic blood pressure and carvedilol may have been missed. Against this possibility is the lack of any trend in favor of a greater relative benefit in patients with lower systolic blood pressure randomized to carvedilol.
- American College of Cardiology Foundation