β-Blocker Plus Statin Cut Perioperative Events


BARCELONA — Treatment with a β-blocker and a statin prior to noncardiac surgery can cut the risk of perioperative cardiac death or myocardial infarction in asymptomatic patients.

In fact, heart rate control with a β-blocker is so effective for preventing perioperative events that it precludes the need for a preoperative assessment of intermediate-risk patients with stress echocardiography, Dr. Don Poldermans said at a joint meeting of the European Society of Cardiology and the World Heart Federation.

In the Dutch Echocardiographic Cardiac Risk Evaluation Applying Stress Echo-II (DECREASE-II) trial, a controlled study with 770 intermediate-risk patients who underwent major vascular surgery, treatment with a β-blocker and no preoperative testing led to outcomes that were as good as those in patients who were evaluated by dobutamine echocardiography followed by angiography and revascularization when needed.

“If a patient is sent for major surgery, such as vascular surgery, but is stable and asymptomatic and has two or fewer risk factors, then they are well-off treated with a β-blocker and a statin” and don't need further testing, said Dr. Poldermans, a professor in the department of anesthesiology at Erasmus University Medical Center in Rotterdam, the Netherlands.

He recommended starting the β-blocker long enough before surgery so that patients reach a resting heart rate of less than 70 beats per minute. In the prospective study, the target rate during and after surgery was 60–65 bpm. Treatment should be with a long-acting β-blocker. In the study, bisoprolol was used for oral treatment; intravenous metoprolol was used in patients unable to take medication orally or by nasogastric tube following surgery.

Results from the DECREASE-II study were published simultaneously with Dr. Poldermans' report at the meeting (J. Am. Coll. Cardiol. 2006;48:964–9). The study was sponsored by Merck KGaA, which markets bisoprolol (Concor) in Europe. Bisoprolol is marketed as Zebeta in the United States by Lederle, under license from Merck KGaA. (Merck KGaA, based in Germany, is not affiliated with Merck & Co., based in the United States.)

The DECREASE-II findings contrast with 2002 recommendations from the American College of Cardiology and the American Heart Association, which called for noninvasive cardiac stress testing for all patients who are scheduled for major vascular surgery and have clinical features associated with increased cardiac risk.

DECREASE-II enrolled a total of 1,476 patients who underwent elective open abdominal-aortic or intrainguinal arterial reconstruction during 2000–2005 at any of five participating centers in Belgium, Brazil, Italy, the Netherlands, and Serbia and Montenegro. After being screened for seven risk factors (see box), patients were stratified into three risk groups.

The 354 (24%) low-risk patients had none of these risk factors, 770 (52%) intermediate-risk patients had one or two risk factors, and 352 (24%) high-risk patients had three or more risk factors. All patients in the study were begun on β-blocker therapy regardless of their risk status, and treatment was continued after surgery with ongoing dosage adjustments to maintain the target heart rate of 60–65 bpm.

The incidence of perioperative cardiac events—cardiac death or myocardial infarction—during the first 30 days after surgery was 0.3% in the low-risk patients, 2.2% in the intermediate-risk patients, and 8.5% in the high-risk patients. After a median of 2 years of follow-up, the event rates were 0.7%, 3.7%, and 14.8% in the low-, intermediate-, and high-risk groups respectively.

The 386 intermediate-risk patients who underwent dobutamine echocardiography, followed by angiography and revascularization if needed, had a 2.3% perioperative event rate, compared with a 1.8% rate in those who weren't evaluated with echocardiography. After 2 years of follow-up, the event rate was 4.3% in patients who had preoperative testing and 3.1% in patients who did not have routine testing.

The value of perioperative statin treatment is now being tested in a prospective, controlled study, DECREASE-IV, which involves coadministration of a statin and β-blocker. But results from less-definitive studies have suggested that statin treatment is another way to lower operative risk.

Results from one of these studies were reported at the meeting. Dr. Poldermans and his associates used data drawn from the more than 100,000 patients who underwent noncardiac and nonvascular surgery at Erasmus University Medical Center during 1991–2000. The cases were 923 patients who died during their postsurgical hospitalization. The controls were 1,846 patients (two controls per case) who did not die. Both β-blockers and statins were used less often in the cases than in the control patients. A statistical analysis showed that treatment with a β-blocker reduced perioperative mortality by about 60%, and that treatment with a statin was independently also linked with a 60% reduction in the mortality rate, reported Dr. Peter G. Noordzij, a researcher who works with Dr. Poldermans in the department of anesthesiology.


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