Perioperative beta-blockers in noncardiac surgery: Evolution of the evidence
ABSTRACTAfter studies in the 1990s suggested that beta-blockers offer substantial benefits when given before surgery, several national organizations endorsed the perioperative use of these drugs as a best practice in certain patients. However, subsequent research has cast doubt on whether it is appropriate to use these drugs as widely as suggested by those early studies.
KEY POINTS
- Beta-blockers reduce perioperative ischemia, but the benefit may be only in high-risk patients undergoing high-risk surgery. Currently, the best evidence supports their use in two groups: patients undergoing vascular surgery who have known ischemic heart disease or multiple risk factors for it, and patients who are already on beta-blockers.
- The Perioperative Ischemic Evaluation (POISE) findings suggest that beta-blockers should be used in the immediate preoperative period only with great caution, after ensuring that the patient is clinically stable and without evidence of infection, hypovolemia, anemia, or other conditions that could make heart-rate titration misleading or use of the drug dangerous.
- When feasible, beta-blockers should be started a month before surgery, titrated to a heart rate of 60 beats per minute, and continued for approximately a month. If the drug is then to be discontinued, it should be tapered slowly.
ANY ROLE FOR BETA-BLOCKERS IN THOSE AT INTERMEDIATE RISK?
Thus, in the past decade, the appropriate perioperative use of beta-blockers, which, after the findings by Mangano et al and Poldermans et al, were seen as potentially beneficial for any patient at risk of coronary disease, with little suggestion of harm, has become more clearly defined, and the risks are more evident. The most compelling evidence in favor of using them comes from patients with ischemic heart disease undergoing vascular surgery; the 2007 ACC/AHA guidelines recommend that this group be offered beta-blockers in the absence of a contraindication (class I recommendation: benefit clearly outweighs risk).6 The guidelines also point out that these drugs should be continued in patients already taking them for cardiac indications before surgery, because ischemia may be precipitated if a beta-blocker is abruptly discontinued.42,43
Additionally, the guidelines recommend considering beta-blockers for vascular surgery patients at high cardiac risk (with a Revised Cardiac Risk Index score of 3 or more), even if they are not known to have ischemic heart disease. This is a class IIa recommendation (the benefit outweighs the risk, but more studies are required).
The guidelines also recommend that beta-blockers be considered for patients who have a score of 0 if they are undergoing vascular surgery (class IIb recommendation) or a score of 1 if they are undergoing vascular surgery (class IIa recommendation) or intermediate-risk surgery (class IIb recommendation). However, in view of the POISE results, these recommendations need to be carefully scrutinized.
These data notwithstanding, beta-blockers still might be beneficial in perioperative patients at intermediate risk.
Start beta-blockers sooner?
To help patients at intermediate risk (such as those with diabetes without known heart disease), we may need to do what Poldermans et al did3: instead of seeing patients only once a day or two before surgery, we may need to do the preoperative assessment as much as a month before and, if necessary, start a beta-blocker at a low dose, titrate it to a goal heart rate, and follow the patient closely up until surgery and afterward.
The importance of heart-rate control was illustrated in a recent cohort study of perioperative beta-blockers in vascular surgery patients,44 in which higher beta-blocker doses, carefully monitored, were associated with less ischemia and cardiac enzyme release. In addition, long-term mortality rates were lower in patients with lower heart rates. And Poldermans et al45 recently performed a study in more than 700 intermediate-risk patients who were divided into two groups, one that underwent preoperative stress testing and one that did not. Beta-blockers were given to both groups, and doses were titrated to a goal heart rate of less than 65. The patients with optimally controlled heart rates had the lowest event rates.
However, the logistics of such a program would be challenging. For the most part, internists and hospitalists involved in perioperative assessment do not control the timing of referral or surgery, and adjustments cannot be made for patients whose preoperative clinic visit falls only a few days before surgery. Instituting a second or third visit to assess the efficacy of beta-blockade burdens the patient and may not be practical.
Are all beta-blockers equivalent?
An additional factor is the choice of agent. While the most significant studies of perioperative beta-blockade have used beta-1 receptor-selective agents (ie, metoprolol, atenolol, and bisoprolol), there is no prospective evidence that any particular agent is superior. However, a recent retrospective analysis of elderly surgical patients did suggest that longer-acting beta-blockers may be preferable: patients who had been on atenolol in the year before surgery had a 20% lower risk of postoperative myocardial infarction or death than those who had been on short-acting metoprolol, with no difference in noncardiac outcomes.46
