Perioperative adverse cardiovascular events among patients who are having noncardiac surgery are relatively common, confer additional risk of other serious complications including death, and add significantly to health care costs. Relatively simple methods exist for risk stratification of these patients, including indices such as Goldman’s original cardiac risk index and Lee’s revised Cardiac Risk Index. However, few effective interventions exist for reducing the incidence of adverse perioperative cardiovascular occurrences and decreasing the associated morbidity and mortality. The risk-stratification schemes mentioned above are based on clinical history and symptoms. In addition to these, noninvasive testing, cardiac catheterization, and, for some subgroups, subsequent myocardial revascularization, together with careful perioperative monitoring, are often cited as reducing the risk of adverse cardiovascular events. In terms of available pharmacologic interventions, the perioperative use of beta-adrenergic-receptor blockers is often advocated as a safe, effective, and relatively inexpensive method of reducing adverse cardiovascular events after noncardiac surgery.

Although the majority of evidence suggests that beta-blockade is effective in reducing cardiovascular events after noncardiac surgery, especially for high-risk surgical patients, many questions currently remain unanswered. For which patients is the perioperative use of beta-blockade actually indicated? Are there patients who could be harmed by such treatment? Does it matter which beta-blocker is used? How early should beta-blockade be started, and how long should therapy continue postoperatively? What is the target heart rate? Is the protective effect mediated by blockade of the beta-adrenergic receptor or is it a heart-rate control effect?

Among the earliest reports of the beneficial effect of perioperative beta-blockade was the randomized trial of atenolol reported by Mangano et al. In this study, a relatively brief exposure to atenolol in the perioperative period was associated with morbidity and mortality improvement measured as late as 2 years after the surgery. Since that publication, numerous studies have been published using various beta-blocking medications in varying doses for varying time intervals in varying patient groups. Most of these show outcome
improvements associated with the use of beta-blockade in the perioperative time frame. Another interesting study, with bearing on the heart-rate control versus beta-adrenergic-receptor-blockade question, was carried out by Wallace et al. using clonidine as a heart-rate control intervention in place of beta-blockade. In this study, 190 patients were randomly assigned to either clonidine therapy or placebo; treatment was begun preoperatively and continued for 4 days after surgery. Thirty-day mortality was 6.2% with placebo, compared with just 0.8% with clonidine; 2-year mortalities were 29.2% and 15.2%, respectively. Most recently, Lindenauer published the results of a large-scale retrospective analysis of patients who underwent noncardiac surgery at one of 329 small to mid-size nonteaching hospitals throughout the United States. Among 122,338 patients who received perioperative beta-blockade there was an apparent relationship between underlying health status and benefit or not from the treatment. Using the revised cardiac risk index (rCRI), patients who had no or only minor cardiovascular risk (rCRI score of 0 or 1) had no benefit, and possibly a worsened outcome, associated with beta-blockade. However, patients with an rCRI score of 2, 3, or 4 had benefit (odds ratio for in-hospital death less than 1) associated with beta-blocker treatment. And perhaps more interesting, this risk reduction improved as the rCRI score increased: the higher the risk, the greater the apparent risk reduction from beta-blockade.

There have also been several larger-scale meta-analyses of the individual publications that appear to show clinical outcome advantage to the use of beta-blockers. Auerbach and Goldman, in 2002, assessed five randomized, controlled trials and reached the conclusion that beta-blockade was likely beneficial in preventing cardiac morbidity. Stevens et al. performed a quantitative systematic review in 2003 of pharmacologic myocardial protection for patients undergoing noncardiac surgery and found that the 11 beta-blockade trials reviewed showed decreased ischemic episodes, reduced risk of myocardial infarction, and reduced risk of cardiac death in the beta-blockade group compared to placebo. They also observed that higher-risk patients received greater benefit from beta-blocker therapy. In 2005, McGory et al. performed a formal meta-analysis of six randomized, controlled trials and concluded that beta-blockade therapy was not only associated with reduced perioperative myocardial ischemia, myocardial infarction, and cardiac mortality but also conferred a reduction long-term cardiac mortality and overall mortality.

Meanwhile, the Agency for Healthcare Research and Quality and others have issued statements strongly supportive of the perioperative use of beta-blockers for patients who are having noncardiac surgery, especially those with increased risks of adverse perioperative cardiovascular events. The American College of Cardiology/American Heart Association (ACC/AHA) Task
Force on Practice Guidelines has recently released an updated guideline specific to perioperative beta-blocker usage. According to this statement, beta-blockers should be continued in surgical patients who are already receiving them for angina, arrhythmias, hypertension, or other ACC/AHA Class I guideline indications. Beta-blockers should be given to patients who are undergoing vascular surgery when ischemia has been noted on preoperative testing. Beta-blockers are probably indicated for patients undergoing vascular, high-risk, or intermediate-risk surgeries who have coronary heart disease or multiple clinical risk factors for increased perioperative cardiovascular risk. Beta-blockers may be considered for patients who are undergoing vascular high-risk or intermediate-risk surgeries who have a single clinical risk factor and for patients who are undergoing vascular surgery with low cardiac risk who are not already on beta-blockers. Finally, beta-blockers should not be given to patients undergoing surgery who have absolute contraindication to beta-blockade. The ACC/AHA recommends that beta-blockers be started several days or weeks before elective surgery with a target resting heart rate of 50 to 60 beats/min—an indication that the patient is receiving the benefit of beta-blockade but not yet evidence-based except for one recent study showing that “tight” heart rate control with beta-blockers was beneficial in patients having vascular surgery procedures (Feringa et al.). According to AHA recommendations, therapy should continue intra- and postoperatively to keep heart rates below 80 beats/min.