The communication from Badgett et al. serves to emphasize that there remain a number of important questions about how to optimize the efficacy of perioperative β blockade. While it is clear that perioperative β blocker reduces mortality,1unresolved issues include use of prophylactic β-blockade in moderate risk patients, choice of medication, optimal dosing intervals, optimal doses, appropriate heart rate targets (e.g. , maximum heart rate vs. average heart rate), routes of administration, optimal strategies for ensuring administration, and, most importantly, strategies to avoid medication withdrawal.1We agree that reanalysis of heart rate data from the atenolol study2,3might address some questions regarding physiologic response and diurnal variation. Unfortunately, the patient population in the atenolol study was limited, with only 200 patients, and we doubt that reanalysis would have sufficient statistical power to definitively answer questions regarding optimal dosing intervals as the dosing was by protocol, and there is little variation. The optimal dosing interval problem is particularly an issue in subgroups of patients with different risk-factor profiles.
There are a number of possible hypotheses to explain the observed differences in mortality between patients treated with atenolol or metoprolol,4including differences in drug metabolism, appropriate dosing intervals, interactions with other medications that affect metabolism such as antidepressants, rates of missed doses, and actual differences in efficacy or pharmacodynamics of the two drugs. We have begun the process of investigating our existing data to define the mechanisms for the observed differences in mortality, but this work is currently incomplete. We do believe that future investigations of perioperative β blockade will need to be informed by an awareness of the above issues, as well as by other evolving issues in β-blockade, including the increasing use of vasodilating β blockers such as carvedilol, as well as declining use of β blockers as first-line agents for hypertension.
*San Francisco Veterans Affairs Medical Center, San Francisco, California. awallace@cardiacengineering.com
