Background: In 2007, the American College of Cardiology and the American Heart Association (ACC/AHA) issued joint guidelines for perioperative beta-blocker use in noncardiac surgery. For noncardiac surgery, beta blockers were recommended for patients already on therapy or for those having vascular surgery with evidence of ischemia on preoperative testing (class I) and possibly for patients having vascular, intermediate, or high-risk nonvascular surgery who were at high risk of cardiac disease or had established cardiac disease (class II).
The Study: Bangalore and colleagues conducted a meta-analysis of trials examining perioperative beta-blocker use from January 1966 to May 2008. All studies reviewed were randomized controlled trials of perioperative beta-blocker use in noncardiac surgery, in patients with or without cardiovascular morbidities that assessed perioperative effectiveness and safety outcomes within 30 days of surgery. Outcomes of interest included 30-day all-cause mortality; cardiovascular mortality; nonfatal myocardial infarction (MI); nonfatal stroke; heart failure; and perioperative bradycardia, hypotension, and bronchospasm.
Results: Thirty-three trials including 12,306 patients having noncardiac surgery were analyzed. Fifty-one percent of patients received perioperative beta blockers, and the remaining 49 percent were assigned to the control group.
Overall, beta blockers did not reduce all-cause mortality, cardiovascular mortality, or heart failure. Risk of nonfatal MIs was reduced (odds ratio [OR] = 0.65; number needed to treat [NNT] = 63) with beta blockade, as was myocardial ischemia (OR = 0.36, NNT = 16). However, beta blockers were associated with a 116 percent increased risk of nonfatal strokes (OR = 2.01; number needed to harm [NNH] = 275), and greater risk of bradycardia (NNH = 22) or hypotension (NNH = 17) requiring intervention. Similar results were noted when only trials with low risk of bias were evaluated, except that all-cause mortality also increased by 28 percent with perioperative beta blockers.
Conclusion: This meta-analysis showed no clear benefit of perioperative beta-blocker use in patients having noncardiac surgery. The authors project that treating 1,000 patients with beta blockers would lead to 16 fewer nonfatal MIs, but at the expense of three additional strokes, 45 cases of perioperative bradycardia, and 59 cases of perioperative hypotension. They recommend avoiding beta blockers in those undergoing noncardiac surgery, unless the patient is already using them for other indications such as heart failure, coronary disease, or previous MI. The authors also recommend that the ACC/AHA guideline committee soften their stance on perioperative beta blockade until conclusive evidence is available.
editor's note: This study builds on the results of the recent PeriOperative Ischemic Evaluation (POISE) trial, which found that perioperative extended-release metoprolol (Toprol XL) for noncardiac surgery was associated with fewer nonfatal MIs (hazard ratio [HR] = 0.73) but greater mortality (HR = 1.33) and more strokes (HR = 2.17).1
The 2007 ACC/AHA guidelines recommending perioperative beta-blocker use relied on a number of small studies that suggested this would reduce the risk of MI or death in noncardiac surgical patients.2 However, several other small studies showed no benefit.3,4 With POISE examining more than 8,000 patients, and the current study, there is now strong evidence that there is greater risk of routine beta-blocker use for this indication than was previously thought.
One drawback of POISE is that beta blockers were started within four hours of surgery, whereas the 2007 ACC/AHA guidelines recommend starting them at least days if not weeks beforehand. The current study did report increased stroke risk with beta blockers started at least one day before surgery, but this secondary result was underpowered to make a conclusive determination. It also tentatively identified that high surgical risk groups (e.g., emergency or vascular surgery) might benefit from beta blockers, but again their population numbers were too small for conclusive determination. If true, however, this would support the ACC/AHA's stronger recommendation (class I) for vascular surgical patients with evidence of ischemia.
Until more information is available, perioperative beta blockers should be used cautiously in noncardiac surgical patients, except in those undergoing high-risk procedures. Physicians should review the potential benefits (e.g., fewer nonfatal MIs) and risks (e.g., increased stroke risk, possible increased mortality) with patients.—k.t.m.