Wisdom of Preoperative Beta-Blockers Questioned

By Charles Bankhead
WEST ROXBURY, Mass., 02 nov 2008-- In noncardiac surgery, preoperative beta-blockers may increase cardiovascular risks despite achieving adequate heart-rate control, especially in patients who are not at high risk, investigators here concluded.
Patients treated with beta-blockers had a higher rate of myocardial infarction at 30 days and 30-day mortality, compared with a control group, Kamal M. F. Itani, M.D., of the Boston VA, and colleagues reported in the October issue of Archives of Surgery.
In the beta-blocker group, patients who died had a significantly higher baseline heart rate, but none of the deaths involved patients considered to be at high cardiac risk.
"Our study adds to the controversy regarding the optimal use of perioperative beta-blockers in patient populations at various levels of cardiac risk," the authors said. "Overall, our data found worse perioperative cardiovascular outcome and worse overall mortality associated with the use of beta-blockers."
"Further investigations in this field with standardizing of beta-blockade regimen and with monitoring of heart rate in populations at various levels of cardiac risk should be pursued," they added.
Evidence linking perioperative ischemic events to a rise in heart rate sparked interest in use of beta-blockers to improve surgical outcomes. However, multiple studies failed to demonstrate a clear benefit, and some studies suggested that perioperative beta-blockers increased surgical risk.
In a 2006 guideline update, the American College of Cardiology and American Heart Association recommended limiting perioperative beta-blockers to two groups of patients undergoing noncardiac surgery: 1. Those already on beta-blockers, and 2. High-risk patients undergoing vascular surgery.
The ACC-AHA guideline recommends a resting heart rate of 50 to 60 bpm and maintenance of a heart rate less than 80 bpm through the intraoperative and perioperative periods.
Previous studies had not evaluated perioperative beta-blockers in patients at low or intermediate risk, the authors said. Additionally, few studies evaluated the optimal drug, dose, regimen, or duration of therapy.
"No definitive consensus has been reached regarding the population at intermediate cardiac risk and the target heart rate needed for effect," they said. In an effort to bring some clarity to the discussion, investigators retrospectively reviewed data on 1,238 patients who received perioperative beta-blockers in conjunction with noncardiac surgery. The patients were stratified by baseline cardiac risk from high to negligible. They were matched with a similar number of patients who had surgery without beta-blockers.
The primary outcome was 30-day stroke, cardiac arrest, myocardial infarction, and mortality, as well as one-year mortality.
Across all levels of baseline risk, patients who received beta-blockers had a significantly lower preoperative heart rate compared with the control group (70 versus 74 bpm, P<0.001).
The beta-blocker group had a 30-day mortality of 2.52% versus 0.25% in the control group (P=0.007) and a 30-day nonfatal MI incidence of 2.94% compared with 0.74% (P=0.03). The 30-day incidence of cerebrovascular accident (0% versus 0.49%) and cardiac arrest (0% versus 0.25%) did not differ between groups, nor did one-year mortality (4.31% versus 2.70%).
Total cardiac morbidity was significantly higher in the beta-blocker group (5.04% versus 1.47%, P=0.003).
Noting that deaths in the beta-blocker group involved patients at low and intermediate risk, the authors said their findings raise questions about the safety of beta-blockers in those patients.
"In addition, the patients who died within 30 days had a clinically and statistically higher preoperative heart rate than did their counterparts [86 versus 70 bpm, P=0.03)]," the authors said. "As subtle as it may be, this finding suggests that a low target preoperative rather than intraoperative heart rate is essential for the protective effect of beta-blockers."
The authors noted several limitations of the study including the fact that it is a retrospective study, and some additional confounding variables might exist.
In addition, they acknowledged, the study population was a predominantly male veteran population and the results might not be applicable to the general population. They also noted that there was no uniform regimen for β-blockade, and data regarding the concomitant use of statins, β-blockers, or antiplatelet therapy were unavailable.
In an invited critique, Todd E. Rasmussen, M.D., of Wilford Hall Air Force Medical Center in San Antonio, wondered whether "use of preoperative beta-blockers" had already categorized patients as high risk.
"It is conceivable, if not likely, that patients in the beta-blocker group were indeed at higher risk, having been identified as candidates for preoperative beta-blocker therapy," said Dr. Rasmussen. "Such patients may not have displayed overt clinical risk . . . to change their risk category but were perceived as having 'enough of a risk' to trigger starting the well-publicized cardioprotective therapy of oral beta-blockade."
The authors and Dr. Rasmussen reported no conflicts of interest.
Primary source: Archives of SurgerySource reference:Kaafarani HMA, et al "Beta-blockade in noncardiac surgery. Outcome at all levels of cardiac risk" Arch Surg 2008; 143: 940-944. Additional source: Archives of SurgerySource reference: Rasmussen TE "Invited critique" Arch Surg 2008; 143: 944.