Current guidelines from the American College of Cardiology Foundation (ACCF) and the American Heart Association (AHA) recommend starting
β-blockers to prevent cardiac events in patients about to undergo intermediate- or high-risk surgery or vascular surgery who have a history of inducible ischemia, coronary artery disease (CAD), or at least one risk factor for CAD.2 However, the majority of the evidence for these guidelines, which were published in 2009 and are in the process of being updated, came from the DECREASE (Dutch Echocardiographic Cardiac Risk Evaluation Applying Stress Echocardiography) trials. These trials have been discredited due to serious methodologic flaws, including falsified descriptions of how outcomes were determined and fictitious databases.3
A new meta-analysis conducted by Bouri et al1 that excluded the DECREASE trials found that, although preoperative β-blockers reduce the rate of certain nonfatal outcomes, they increase the risk for death and stroke.
STUDY SUMMARY
Preop β-blockers do more harm than good
Bouri et al1 conducted a meta-analysis of published RCTs evaluating preoperative β-blockers versus placebo for patients undergoing noncardiac surgery. Of the 11 studies that met eligibility criteria, two were the discredited DECREASE trials. Thus, Bouri et al1 analyzed nine high-quality RCTs that included 10,529 patients.
Most studies included patients undergoing vascular surgery. Some studies also included intra-abdominal, intrathoracic, neurosurgic, orthopedic, urologic, and gynecologic surgeries. β-Blockers were started no more than a day before surgery and were discontinued at hospital discharge or up to 30 days postop. Metoprolol was used in five trials, bisoprolol in one trial, atenolol in two trials, and propranolol in one trial. The primary endpoint was all-cause mortality within 30 days.
A total of 5,264 patients were randomly assigned to receive β-blockers and 5,265 to placebo. There were 162 deaths in the β-blocker group and 129 deaths in the placebo group. Patients who received β-blockers had a 27% increased risk for all-cause mortality (risk ratio [RR] = 1.27). The number needed to harm was 160.
Six of the studies also evaluated rates of nonfatal MI, nonfatal stroke, and hypotension. β-Blockers lowered the risk for nonfatal MI (RR = 0.73) but increased the risk for nonfatal stroke (RR = 1.73) and hypotension (RR = 1.51).
This meta-analysis was dominated by the 2008 Peri-Operative ISchemic Evaluation (POISE) trial, an RCT that compared placebo to extended-release metoprolol (100 mg 2 to 4 h before surgery, followed by 200 mg/d for 30 d), in 8,351 patients with, or at risk for, atherosclerotic disease.4 While β-blockers reduced the risk for MI and atrial fibrillation, they increased the risk for mortality and stroke, likely due to drug-induced hypotension. The slightly larger-than-typical doses of β-blockers used in this study may have contributed to the excess mortality.
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