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Higher Risk of Death and Stroke in Patients Given Beta-Blockers After Non-Cardiac Surgery (POISE Trial)

LONDON, May 12, 2008-A randomised trial has shown that patients given beta blockers after non-cardiac surgery1 have a higher risk of death or stroke than those given placebo. However the patients given beta blockers were less likely to suffer non-fatal heart attack. These are the conclusions of authors of an Article published early Online and in an upcoming edition of The Lancet.

Worldwide, about 100 million adults undergo non-cardiac surgery every year, which is associated with major complications which occur in 1 million of these patients. Non-cardiac surgery causes a rise in catecholamine concentrations that results in an increase in heart-rate, blood pressure, and fatty acid concentrations, which in turn increases the oxygen demands of the heart. beta blockers reduce the effects of increased catecholamine levels and thus could prevent cardiovascular complications; however previous studies to test this theory have delivered mixed results. Dr P. J. Devereaux, McMaster University, Hamilton, ON, Canada, and colleagues from the POISE2 study group did a randomised controlled trial to investigate the effects of peri-operative beta blockers.

The study was done in 190 hospitals across 23 countries3. 8351 patients with, or at risk of atherosclerotic disease who were undergoing non-cardiac surgery were randomised to receive the beta blocker metoprolol succinate (4174 patients) or placebo (4177). Treatment was started 2–4 hours before surgery and continued for 30 days. The primary endpoint was any of: cardiovascular death, non-fatal heart attack, or non-fatal cardiac arrest.

The researchers found that fewer patients in the metoprolol group reached the primary endpoint (244) than in the placebo group (290), making those in the metoprolol group 16% less likely to reach this endpoint. Fewer patients in the metoprolol group (176) than the placebo group (239) had a heart attack, a reduction in risk of 27% for the metoprolol group. However, there were more deaths in the metoprolol group (129) than the placebo group (97), equalling and increased risk of 33% for the metoprolol group; and more patients had a stroke in the metoprolol group (41) than the placebo group (19)—more than double the risk.

The authors say: "Our results suggest that for every 1000 patients with a similar risk profile undergoing non-cardiac surgery, extended-release metoprolol would prevent 15 patients from having a heart attack, three from undergoing cardiac revascularisation4, and seven from developing new and significant atrial fibrillation5. The results also suggest that extended-release metorprolol would result in an excess of eight deaths, five patients having a stroke, 53 experiencing clinically significant hypotension6, and 42 experiencing clinically significant bradycardia7 for every 1000 treated."

They conclude: "For every 15 patients who participated in POISE, one had a cardiovascular death, non-fatal heart attack, non-fatal cardiac arrest, or non-fatal stroke at 30 day follow-up. In view of the large numbers of individuals undergoing surgery and the high risk of cardiovascular complications, more large trials are needed urgently...Our results highlight the risk in assuming a perioperative beta blocker regimen has benefit without substantial harm. Patients are unlikely to accept the risk associated with perioperative extended-release metoprolol. "

In an accompanying Comment, Dr Lee A Fleisher, University of Pennsylvania School of Medicine, Philadelphia, PA, USA, and Dr Don Poldermans, Erasmus Medical Centre, Rotterdam, Netherlands, agree that the POISE study clearly shows that acute administration of higher-dose beta blocker therapy in the perioperative period is associated with greater risk than benefit. But they also discuss the differing implications the study could have on daily clinical practice, depending on the indication for beta blockers in the individual patient.

They also discuss that other protocols using a low dose beta blocker regimen have established a beneficial effect on post operative outcome without an increased incidence of stroke. They recommend the use of beta blockers carefully in the perioperative period, in a low dose, and supervised by clinicians who are experienced in haemodynamic care during surgery.

Dr P.J. Devereaux (this is how Dr Devereaux is known) McMaster University, Hamilton, ON, Canada. T) +1 905 525 9140 ext 22900

Dr Lee A Fleisher, University of Pennsylvania School of Medicine , Philadelphia, PA, USA. T) +1 215-662-3738 / +1 215-349-5659

Note to Editors

1 all surgery except heart surgery.

2 POISE: PeriOperative ISchemic Evaluation.

3 23 countries: UK, Australia, Canada, New Zealand, Argentina, Hong Kong, Malaysia, Singapore, Brazil, China, Colombia, Ecuador, Finland, Hungary, India, Mexico, Norway, Peru, Spain, Sweden, Thailand, Cuba, El Salvador.

4 cardiac revascularisation: coronary artery bypass graft (CABG) surgery or angioplasty.

5 atrial fibrillation: a type of irregular heartbeat.

6 hypotension: a low blood pressure that required medical treatment.

7 bardycardia: a low heart rate that required medical treatme

Posted: May 2008