Published in the December 2005 issue of Today’s Hospitalist
A decade ago, the field of hospital medicine was jolted by new research that suggested giving beta-blockers to patients in the perioperative period significantly lowered the risk of myocardial infarction and cardiac death associated with surgery.
The studies were not definitive, but they prompted medical groups, including the American Heart Association and the American College of Cardiology, to recommend the drugs in some patients. Physicians were urged to focus in particular on patients at high risk of cardiac complications following surgery.
National organizations like the National Quality Forum and the Agency for Healthcare Research and Quality followed suit, declaring perioperative beta-blockers a key strategy in driving down post-surgical complications. Not surprisingly, many hospitals embraced the recommendations, with some going one step farther and using the drugs more aggressively than the guidelines recommended. Now, however, new data are questioning the effectiveness of perioperative beta-blocker prophylaxis, particularly when it comes to low-risk patients.
Two studies published over the summer found that the drugs are useful in preventing post-operative heart trouble, primarily in patients who have multiple risk factors like diabetes, kidney disease, a previous heart attack or atherosclerosis. But the studies also found that beta-blockers may provide little to no preventive effects in healthier patients. Data, in fact, show that in patients with little or no risk of cardiac complications from surgery, the drugs may even cause more harm than good in the form of bradycardia and hypotension, two conditions that can be lethal if not treated promptly.
“There are patients for whom the general medical community has accepted the value of betablockers to prolong life and prevent heart attacks,” says Kim Eagle, MD, chief of clinical cardiology and clinical director of the University of Michigan cardiovascular center in Ann Arbor. “If you move away from those, however, it’s much less clear what we should do. My tendency is to stay conservative. The potential to over-prescribe beta-blockade in the absence of data is large enough.”
The American College of Cardiology is now revisiting its guidelines on the matter, and Dr. Eagle expects the document will reflect the latest data on perioperative beta-blockers. “They will slightly increase the emphasis for very firm indications, but they will probably argue against overuse in other groups,” says Dr. Eagle, who helped write the earlier recommendations that initially included perioperative beta-blockers.
A growing issue for hospitalists
Heart-related complications following surgery are a significant problem in the United States and elsewhere. Data show that about 1 percent “and possibly more “of patients who undergo a major noncardiac operation, such as vascular or emergency surgery, suffer myocardial infarction or some other serious postoperative event. The figure approaches 30 percent in patients undergoing high-risk vessel procedures like correcting an aneurysm.
Exactly why surgery can lead to cardiac complications isn’t clear. The leading theory is that the trauma of an operation causes an adrenergic flush that stresses the heart. For patients in whom the organ is already vulnerable, this extra strain can trigger an infarction.
Beta-blockers make sense in the surgical setting, experts say, because they ease the heart’s response to adrenergic stimulation, dampening the heart rate, lowering its oxygen needs and reducing blood pressure.
The issue is becoming ever more pertinent for hospitalists, particularly in light of the growing number of co-managed surgery patients. While hospital medicine is already booming and expected to reach up to 30,000 physicians by the end of the decade, some experts have said that hospitalists’ growing involvement in co-managing surgical patients could eventually push that number to 50,000.
“The vast majority of hospitalists are involved in the care of surgical patients, through consultation and comanagement,” says Peter K. Lindenauer, MD, a hospital medicine specialist in the division of health care quality at Baystate Medical Center in Springfield, Mass. “On a very basic level, they are important members of the perioperative team.”
The role of hospitalists in surgical patients is growing, Dr. Lindenauer says, in part because of the move toward public reporting of hospital quality and pay for performance, along with the government’s recent push to reduce complications of surgery.
Low-risk patients
Dr. Lindenauer was the lead author of a July 28, 2005, New England Journal of Medicine study that compared outcomes in more than 660,000 noncardiac surgery patients, roughly 20 percent of whom had received perioperative beta-blockers.
The retrospective study was based on records from 329 hospitals between the years 2000 and 2001. It found that beta-blockers cut the risk of premature death by nearly 40 percent in patients with four or more risk factors for cardiovascular trouble (as defined by the revised cardiac risk index, or RCRI) going into the operating room. Mortality was reduced in 29 percent of individuals with an RCRI of three, and in 12 percent of those with an RCRI of two.
But the benefit tailed off in healthier patients, and the drugs had no preventive effect in patients with one or no cardiac risk factors. Indeed, those in the lowest-risk group appeared to have increased odds of dying in the hospital if they took the drugs.
“On one level, our findings support the current recommendations to give beta-blockers to high-risk patients,” Dr. Lindenauer says. “Yet they also suggest that physicians need to take care when selecting patients for therapy. These are not drugs that should be given to every patient undergoing major noncardiac surgery.”
Tempering expectations
The New England Journal article was preceded by a metaanalysis published July 4 in the online edition of the British Medical Journal. That study, which included 22 previous studies covering more than 2,400 patients, failed to find a strong benefi t from beta-blockers in the perioperative setting when considering the combined outcomes of cardiovascular death, non-fatal myocardial infarctions, and non-fatal cardiac arrests over a 30-day period.
And as with Dr. Lindenauer’s study, the BMJ article reported a slightly increased risk of serious hypotension and more than a two-fold greater risk of bradycardia in people taking the drugs.
P.J. Devereaux, MD, a cardiologist at McMaster University, in Hamilton, Ontario, and leader of the meta-analysis, says his research, along with a number of other recent trials, raise serious questions about the effectiveness of beta-blockers in all patients, not just those at low risk of cardiac events.
“Given the limitations of the data,” he explains, “it doesn’t make sense that we are in this situation where many have made strong recommendations that physicians should give patients beta-blockers around the time of surgery. People were comfortable with this drug, and it works in other settings, so they jumped on the bandwagon assuming it would work around the time of surgery.”
Dr. Devereaux says he believes that beta-blockers could have a place in perioperative medicine, but he says that larger and higher quality studies are needed fi rst. He and his colleagues are now enrolling patients in a large randomized, controlled study of perioperative beta-blockers. (They already have more than 5,000 patients and hope to include another 3,000 to 5,000.)
Dr. Devereaux hopes this new study can help settle the question of whether beta-blockers are beneficial for patients undergoing surgery. For now, he says, hospitalists who do prescribe the drugs should do so knowing “that the evidence is encouraging, but it’s weak.”
What’s more, physicians need to temper their expectations with a healthy dose of realism. In general, he says, beta-blockers cut the risk of heart attacks and other cardiac morbidity by about 25 percent or so. As a result, there’s no reason to think they’ll do better in the surgery setting. “We won’t find drugs that have 75 percent reduction in risk,” Dr. Devereaux explains.
Interpreting the data
So how should hospitalists interpret the latest data? Experts urge physicians to be cautious, in part because both studies suffered from limitations.
The New England Journal article, for example, could not assess why patients were receiving beta-blockers after surgery. In some cases, patients may have received the drugs for existing high blood pressure or because they’d suffered a heart attack in the recovery room.
Researchers couldn’t determine the dose of beta-blockers patients were using, which raises questions about whether a lack of benefit might reflect an insufficient dose. And because the study was based on observational, not prospective, data, there are concerns that data were not optimally adjusted for patient risk.
Amir Jaffer, MD, medical director of the Cleveland Clinic’s internal medicine preoperative assessment consultation and treatment (IMPACT) center and a practicing hospitalist, warned against making too much of the Canadian research. In order to account for uneven quality in the previous studies they analyzed, the Canadian researchers occasionally chose to use confidence intervals of 99 percent instead of the conventional 95 percent.
In other words, they set the bar for beta-blockers higher than most other researchers, which may have painted a more negative picture. Dr. Jaffer notes that when he reassessed the findings using a 95 percent threshold, the benefits of beta-blockers appeared to be statistically significant.
Experts say that for the time being, prescribing beta-blockers to surgery patients will be something of a judgment call, even if it is one that will be guided by the growing number of quality improvement efforts that focus on this area.
“Hospitalists will have an important role in ensuring [beta-blockers] are used and used well,” says H. Quinny Cheng, MD, a hospitalist at the University of California, San Francisco.
A focused approach
In practical terms, Dr. Cheng says, the new evidence means that hospitalists should focus their attention on giving beta-blockers to people with established heart and vessel disease, diabetes, and a history of heart attacks or strokes. Similarly, patients with signs of kidney failure and other end-organ disease, as well as those facing high-risk surgeries “especially vascular procedures “should be viewed as having a higher risk score, he adds.
“If you have limited resources,” Dr. Cheng explains, “the effort and goal should be the high-risk patients. They should get the bulk of your attention. For patients who are not at very high risk for post-operative cardiac complications, there isn’t a compelling reason to use a beta-blocker based on these data.”
“You don’t need to change your practice significantly,” Dr. Jaffer echoes. “Still give beta-blockers, but carefully look at which of the risk index criteria patients have.”
If they have two or more risks, he explains, it’s reasonable to prescribe the drugs. “But with a score of one or zero,” Dr. Jaffer adds, “you may want to reconsider.”
Tightening the eligibility for perioperative betablocker treatment could affect the overall number of patients receiving the drugs. Dr. Jaffer says that based on data of more than 10,500 patients from his preoperative center, there is still plenty of room for improvement.
In an informal review of his center’s data, Dr. Jaffer examined patients who were at least 65 years old and had hypertension or another risk factor. That process, which he conducted in 2004, found that half of the patients qualified for perioperative beta-blockers.
Of those patients, 16 percent were already taking the drugs, another 8 percent were put on them, and 26 percent could have received them but did not, suggesting significant under-treatment. Dr. Jaffer estimates that excluding patients with fewer than two of the risk indices could reduce the last figure to 20 percent, still a sizeable gap between eligibility and receipt of the drugs.
Alternative therapies
What, if anything, can be done for surgery patients in whom beta-blockers are no longer a clear option? Several possibilities exist, according to Dr. Cheng.
Alpha-2 agonists such as clonidine have shown promise when it comes to reducing perioperative mortality, although the results in clinical trials have not reached statistical significance. One meta-analysis did find a marked benefit, Dr. Cheng notes, but it included drugs not approved for use in the United States.
“I suspect that clonidine never caught on because of the lack of a high profile study with definitive, dramatic results,” Dr. Cheng says. “The role of the alpha-2 agonists is still undefined, but they might be an alternative when beta-blockers are contradicted in a patient at high risk for perioperative cardiac complications.”
However, clonidine lowers blood pressure, so adding it to beta-blocker therapy could limit the ability to increase the doses of latter medication, making combination therapy unlikely, Dr. Cheng says.
Finally, statins have been shown in both retrospective studies and at least one randomized, controlled trial to prevent post operative cardiac complications and death.
“The data are still quite preliminary for statins, but the outlook is hopeful,” Dr. Cheng says. What’s more, he adds, statins could be added to beta-blocker treatment. Indeed, a large study is now looking at the two drugs in the perioperative setting.
For now, clinicians will have to wait for more data before the beta-blocker picture becomes clearer. “The bottom line is that these are interesting times,” Dr. Lindenauer says.
Adam Marcus is a New York-based freelance writer specializing in health care.
