POISE trial: Metoprolol increases the risk of death and stroke around the time of non-cardiac surgery

Beta-blocker drugs may help prevent myocardial infarction during surgery, but they may increase the risk of death and major stroke.

POISE is the world’s largest randomized trial addressing perioperative cardiac complications. POISE evaluated the effects of a beta-blocker versus placebo given to patients around the time of surgery.

“ POISE demonstrates that a beta-blocker given around the time of surgery decreases a patient’s risk of a myocardial infarction but increases their risk of a major stroke and death,” said P.J. Devereaux, POISE co-principle investigator, McMaster University, Hamilton, Canada.

Worldwide approximately 100 million adults have major non-cardiac surgery each year. Among them, more than one million will suffer a major heart complication such as a heart attack or death.

Surgery increases patients’ catecholamines, or stress hormones, which increase the heart’s requirement for oxygen. The stress on the heart can lead to serious events like a myocardial infarction. Because beta-blockers reduce the effects of increased catecholamines some physicians believed they may prevent serious heart complications around the time of surgery.

“ Initial small trials suggested beta-blockers were beneficial around the time of surgery but more recent moderate sized trials did not show any benefit,” Homer Yang, POISE co-principal investigator, University of Ottawa, Ottawa, Canada. “ We undertook POISE to provide a clearer understanding of the effects of a beta-blocker around the time of surgery.”

“A major accomplishment of POISE was that anesthesiologists, cardiologists, internists, and surgeons at 190 centres in 23 countries came together and randomized 8,351 patients - more than 4 times as many patients than all the previous perioperative beta-blocker trials combined. Such efforts are rare, but essential in order to make progress in the management of these patients,” said Salim Yusuf, POISE steering committee chair, McMaster University, Hamilton, Canada.

The POISE Trial randomized 4,174 patients to receive extended-release Metoprolol succinate ( Lopressor, Toprol XL ) and 4,177 patients to receive placebo starting two to four hours before surgery and continuing for 30 days after surgery.

Fewer patients in the Metoprolol group ( 176 ) than in the placebo group ( 239 ) suffered a myocardial infarction, indicating that patients receiving Metoprolol were 27 percent less likely to suffer a heart attack. However, 129 Metoprolol patients compared to 97 placebo patients died, indicating that patients receiving Metoprolol were 33 percent more likely to die. Further, 41 Metoprolol patients versus 19 placebo patients suffered a stroke, indicating that patients receiving Metoprolol had more than double the risk of a stroke.

Considering the myocardial infarctions less than one-third of these patients also had a complication of their heart attack like heart failure. In contrast more than half of the patients who suffered a stroke were left incapacitated or needing help with everyday activities.

The POISE results suggest for every 1,000 patients with a similar risk profile who have noncardiac surgery, Metoprolol will prevent 15 patients from having a myocardial infarction, three from having angioplasty or coronary artery bypass surgery, and seven from developing new atrial fibrillation.

The results also suggest that for every 1,000 patients, Metoprolol would cause eight patients to die, five patients to have a stroke, 53 patients to experience a low blood pressure that would require treatment, and 42 patients to experience a low heart rate that would require treatment. Analysis of the POISE data suggests that Metoprolol increased the risk of death and stroke by increasing the risk of the low blood pressures that required treatment.

Considering the implications of the POISE results Devereaux stated, “ For more than a decade guidelines have recommended giving beta-blockers to patients having noncardiac surgery. Even if only 10% of physicians acted on the guideline recommendations throughout the last decade, 100 million patients would have received a beta-blocker around the time of surgery. If the results of POISE are widely applicable, throughout the last decade 800,000 patients would have died prematurely and 500,000 patients would have suffered a stroke because they were given a beta-blocker around the time of surgery. ”

“ This highlights the risk in assuming a perioperative beta-blocker regimen has benefit without substantial harm, and the importance and need for large randomized trials in the surgical setting. ”

Source: McMaster University, 2008


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