While use of perioperative β-blockers is a widely accepted practice when managing patients undergoing cardiac surgery, using these medications in people who receive non-cardiac surgery is controversial. Years ago, perioperative β-blockade was recommended liberally for patients undergoing non-cardiac surgery after early research demonstrated initial success in patients with cardiac disease. However, this recommendation was based on findings from randomized clinical trials with small samples that may not have included the broad spectrum of patients seen in routine clinical practice.
“While some of the initial studies found a benefit by using β-blockade in non-cardiac surgery, other investigations have shown no advantage to this practice,” says Mark L. Friedell, MD. “In fact, some trials have indicated that patients undergoing non-cardiac surgery could be at greater risk for hypotension and stroke if they use β-blockers.” This has created considerable uncertainty about the use of perioperative β-blockers, particularly in patients at low risk of myocardial ischemic events.
Examining the Effects
Dr. Friedell and colleagues had a study published in JAMA Surgery in which they performed a retrospective observational analysis of patients undergoing surgery in Veterans Affairs (VA) hospitals over a 5-year period. Use of β-blockers was established if a dose was ordered at any time between 8 hours before surgery and 24 hours after the procedure. The authors assessed 30-day mortality outcomes after perioperative β-blockade in patients undergoing non-cardiac surgery with different levels of cardiac risk.
For the study, the authors analyzed demographics, diagnosis and procedural codes, medications, perioperative laboratory values, and dates of death. They then used a four-point cardiac risk score that was calculated by assigning one point each for renal failure, coronary artery disease, diabetes, and surgery in a major body cavity, such as the abdomen or chest. Data were collected and reviewed on more than 326,000 VA patients in the total cohort, including over 314,000 undergoing non-cardiac surgery and more than 12,000 who had cardiac surgery.
Risk Factors Matter
According to the results, the use of β-blockers lowered the 30-day mortality rate significantly in patients with three to four cardiac risk factors undergoing non-cardiac surgery. No significant mortality effect was observed among non-cardiac surgery patients with one to two cardiovascular risk factors. “Importantly, we found that β-blockade resulted in a significantly higher chance of death in patients with no risk factors undergoing non-cardiac surgery,” says Dr. Friedell (Figure).
The study team noted that they did not observe similar results in patients who underwent cardiac surgery. None of the terms in the analysis of the cardiac surgery group were significant. In addition, there were no consistent patterns of the effect of β-blocker use on mortality with regard to the number of cardiac risk factors.
Considering the Controversy
Despite years of research and many studies, the use of perioperative β-blockade in non-cardiac surgery still remains uncertain for low-risk patients. “The investigations on this particular topic have swung from positive to negative,” says Dr. Friedell. “Complicating matters is that some have contradicted one another while others have been labeled as deceitful. This is why our research is important to clinicians who are considering using β-blockers in patients undergoing non-cardiac surgery.”
Cardiology guidelines for β-blockers in the United States have been modified significantly in the past decade as more evidence continues to emerge. More recently, guidelines have recommended that β-blocker therapy should be continued in patients undergoing non-cardiac surgery who are already taking them chronically prior to their operation. “Patients undergoing non-cardiac surgery who are already taking chronic β-blockers should not stop using these medications,” Dr. Friedell says. “However, we shouldn’t routinely administer perioperative β-blockers on the day of surgery or 1 to 2 days before the procedure because this appears to increase the risk of death.”
Dr. Friedell notes that the study was not powered to determine the timing of when β-blockers were started among the participants. It was unclear whether patients were first given the β-blocker in the hospital or if it was a home medication. It also was unknown if patients were first given a β-blocker preoperatively or postoperatively during the hospitalization.
“It will be challenging to address all of the aspects of the controversy surrounding perioperative β-blocker use in non-cardiac surgery, but findings from our study illustrate the importance of not starting these drugs perioperatively in patients with no cardiovascular risk factors,” says Dr. Friedell. “On the other hand, if patients have three or four cardiovascular risk factors, then they should be considered a good candidate for β-blockers.” He adds that this latter group of patients should also be referred to cardiologists to optimize outcomes and address other heart-related issues that may arise during their care.
Friedell ML, Van Way CW, Freyberg RW, Almenoff PL. β-Blockade and operative mortality in noncardiac surgery: harmful or helpful? JAMA Surg. 2015;150:658-664. Available at: http://archsurg.jamanetwork.com/article.aspx?articleid=2294293.
Devereaux PJ, Yang H, Yusuf S, et al; POISE Study Group. Effects of extended-release metoprolol succinate in patients undergoing non-cardiac surgery (POISE trial): a randomised controlled trial. Lancet. 2008;371:1839-1847.
Task Force for Preoperative Cardiac Risk Assessment and Perioperative Cardiac Management in Noncardiac Surgery, European Society Of Cardiology (ESC). Guidelines for preoperative cardiac risk assessment and perioperative cardiac management in noncardiac surgery. Eur Heart J. 2009;30:2769-2812.
American College of Cardiology Foundation and American Heart Association Task Force. 2009 ACCF/AHA focused update on perioperative beta blockade incorporated into the ACC/AHA 2007 guidelines on perioperative cardiovascular evaluation and care for noncardiac surgery. J Am Coll Cardiol. 2009;54:1-108