Baffled by beta-blockers

For hospitalists weighing whether to prescribe a beta-blocker perioperatively, recent updated guidelines provide some helpful indications, but significant questions remain.

For hospitalists weighing whether to prescribe a beta-blocker perioperatively, recent updated guidelines provide some helpful indications, but other outstanding—and significant—questions remain, according to physicians in the field.

The updated guidelines, jointly released by the American College of Cardiology (ACC) and the American Heart Association (AHA), sought to address some concerns about beta-blocker prescribing that developed following the prior guidelines' release in 2007, said Lee A. Fleisher, MD, professor and chair of anesthesiology at the University of Pennsylvania School of Medicine in Philadelphia. He also co-authored the new guidelines published last November in the journal Circulation.

Photo by Thinkstock
Photo by Thinkstock

It became clear that the beta-blocker recommendations—the only section of the 2007 perioperative guidelines for noncardiac surgery to be updated—needed to be revisited after a large-scale and influential study was published, Dr. Fleisher said.

The study, called POISE and involving 8,331 patients, identified fewer heart attacks in those who took beta-blockers. But those benefits were offset by other harmful consequences, including stroke and clinically significant hypotension, according to the results, published May 2008 in the journal Lancet.

Dr. Fleisher, who chaired the writing committee for the 2007 ACC/AHA perioperative guidelines, worried that physician practice might have swung too far in the other direction following the POISE findings. “My sense is that people had already stopped using beta-blockers and our fear was that they were even stopping patients previously on them,” he said.

The updated 2009 guidelines reiterate the importance of continuing beta-blockers in patients already on the drugs. But they downgrade another recommendation regarding their use in vascular surgery patients at high cardiac risk—including those with evidence of ischemia during pre-surgical screening—from class I to class II.

Other protective measures also were emphasized, including titrating the dose to the individual patient, starting well before a planned procedure. In fact, the guidelines flatly state that failing to adjust high-dose beta-blockers for individual patients new to the drug is “not useful and may be harmful.”

The ACC/AHA experts assumed a more conservative stance than their European peers, who also published recommendations last year in the European Heart Journal. Those guidelines, developed by a task force of the European Society of Cardiology, strongly recommended continuing beta-blockers. In addition, they gave a class I recommendation to use the drugs in patients undergoing high-risk surgery, those with heart disease or those with positive stress tests.

Gaps and questions

Where does this leave physicians, and specifically hospitalists, who are on the front lines of making these decisions? The ACC/AHA statement “dialed back appropriately in view of what we know now,” said Vineet Chopra, FACP, a hospitalist and clinical assistant professor of medicine at the University of Michigan Health System in Ann Arbor. “I think it's a very judicious statement, it's a very appropriate statement, because clearly we were going too far.”

Still, what physicians are “left with now is basically a mess,” said Dr. Chopra, who co-authored a Journal of the American Medical Association commentary about the ongoing beta-blocker uncertainties, published in February 2010.

“The problem is that we don't know which drug works best,” he said. “We don't know which dose works best. We certainly don't know when to start them in relation to surgery. And we don't know which patients should be getting them, except for the ones already on it. And so it seems like we are left with more questions than answers.”

One difficulty with extrapolating the POISE results is the hefty size of the dose involved: 100 mg of oral extended-release metoprolol (versus a matching placebo). “They picked a gigantic starting dose,” said Andrew Auerbach, FACP, director of research for the division of hospital medicine at University of California, San Francisco.

The study investigators also started the drug within four hours of surgery, allowing little opportunity to monitor and adjust the dose, Dr. Auerbach said.

If researchers had titrated and followed the POISE patients well before surgery, would the results have been different? At this point, there is an absence of evidence on that outstanding issue, Dr. Fleisher said.

The best time frame for dispensing the medication also is unclear, Dr. Fleisher said. While two weeks before surgery wouldn't pose a problem for many physicians, that decision becomes more difficult as the time frame shortens, he said.

“How far in advance is it appropriate to start beta-blocker therapy and titrate it and feel comfortable,” he said, “that you will get the beneficial effects of a reduced incidence of myocardial infarction shown in POISE . . . and many other studies in the high-risk patient, but without the increased stroke and mortality demonstrated in POISE?”

Continued uncertainty regarding some beta-blocker issues doesn't warrant avoiding the drugs in other, more clear-cut scenarios, Dr. Fleisher said. For example, he said, “One of my biggest concerns is that people will stop using beta-blockers to treat or control tachycardia.”

Earlier intervention

Dr. Auerbach has scaled back his beta-blocker prescribing practices in the wake of the POISE trial. “I tend to be more concerned about the risks now than I used to be,” he said. Still, both the European and the American beta-blocker recommendations might be correct, given differing approaches to preoperative screening and evaluation, he said.

In Europe, it's easier to prescribe a beta-blocker because patients typically visit a clinic or hospital before surgery, sometimes as early as a month prior, Dr. Auerbach said. (The European Society of Cardiology recommends that the beta-blocker dose be titrated and started a week to 30 days before surgery.) But that scenario is relatively rare in the United States, said Dr. Auerbach, who usually doesn't see his patients until six to 24 hours before the operation.

At that time, Dr. Auerbach tends not to prescribe beta-blockers unless the patient is very high risk, which he describes as someone who is undergoing vascular surgery, has multiple risk factors, and has diagnosed or highly suspected heart disease. Given that primary care doctors are more likely now to prescribe beta-blockers to high-risk patients, the dilemma is less likely to fall in the lap of the hospitalist, he said. “The subset of people we need to start on beta-blockers is becoming smaller and smaller.”

Some other hospitalists, such as Peter Kallas, MD, continue to adopt a more aggressive approach than is outlined in the ACC/AHA guidelines. Dr. Kallas said that he'll consider a beta-blocker for patients undergoing moderate to high-risk surgeries who either have heart disease or at least two risk factors, such as congestive heart failure or diabetes.

“We are big believers in identifying the right person for the drug and then starting it days to weeks in advance of surgery and titrating it to a heart rate of 55 to 65 (beats per minute),” said Dr. Kallas, medical director of the perioperative medicine consult service at Northwestern University in Chicago. “We have not seen the strokes that are reported in recent studies.”

The perioperative clinic doesn't typically handle urgent or cardiac surgery patients, which provides the luxury of some monitoring time, Dr. Kallas said. Roughly two-thirds of patients are evaluated a week or more before surgery. They are most likely to be undergoing general, orthopedic or neurosurgical procedures.

Since the POISE trial, Dr. Kallas has adjusted the time window in which he'll start beta-blockers, avoiding them if the surgery is five days or fewer away, unless there's a pressing need. “We don't shotgun it, unless somebody has unstable angina,” he said.

Ultimately, the beta-blocker decision rests upon an individual physician's experience and comfort level, Dr. Kallas said.

“I feel like I'm somewhat of an insider who has used this drug for a long time and haven't seen the stroke effects, so I feel comfortable promoting it,” Dr. Kallas said. “I think the pendulum has swung too far the other way and it has scared away internists and anesthesiologists. I don't think it's scared away most cardiologists and people who focus on this topic.”