β Blockers Increase Risk Of Death And Stroke After Non-Cardiac Surgery (The POISE Trial)

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Main Category: Cardiovascular / Cardiology
Also Included In: Clinical Trials / Drug Trials;  Endocrinology
Article Date: 15 May 2008 - 0:00 PDT

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Patients given β blockers after experiencing surgery other than heart surgery are at a higher risk of death or stroke than those who are given a placebo, according to a randomized trial published on May 13, 2008 in The Lancet. These same patients administered β blockers , however, had a lower chance of a non-fatal heart attack.

Non-cardiac surgery is performed on approximately 100 million adults every year. Major complications associated with these surgeries occur in one million of these patients. Namely, these surgeries are associated with a rise in concentrations of catecholamines such as dopamine, epinepherine, and norepinephrine. This in turn, causes an increase in heart-rate, blood pressure, and in the concentrations of fatty acids, which further increases the oxygen demands on the heart.

β blockers are thus administered to reduce the effects of these catecholamines, which could prevent cardiovascular complications. That said, efforts to test this theory have yielded mixed results. To examine this, Dr P. J. Devereaux, McMaster University, Hamilton, ON, Canada, and colleagues performed the POISE Trial (PeriOperative ISchemic Evaluation), which investigated the effects of peri-operative β blockers using a randomized, controlled study.

Performed in 190 hospitals across 23 different countries, the study evaluated 8,351 patients with, or at risk of atherosclerotic disease who were undergoing non-cardiac surgery. The subjects were randomized to receive the β blocker metopolol succinate (4,174), or the placebo (4,177). Treatment began 204 hours before surgery and was continued for 30 days following. The primary endpoints were any cardiovascular death, non-fatal heart attack, or non-fatal cardiac arrest. 

Fewer patients in the metoprolol group reached the primary endpoint than the placebo group (244 versus 290 respectively,) which made those in the metoprolol group 16% less likely to reach this. Fewer patients in the metoprolol group than the placebo had a heart attack (176 versus 239), with a risk reduction of 27%.

However, overall, there were more deaths in the metoprolol group than the placebo (129 versus 97,) which evened out and increased the risk of 33% for the metoprolol group. Additionally, more patients had a stroke in the metoprolol group than the placebo (41 versus 19) indicating they had more than double the risk of this complication.

The authors summarized the results in the following way: "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 revascularisation, and seven from developing new and significant atrial fibrillation. 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 hypotension, and 42 experiencing clinically significant bradycardia for every 1000 treated."

In conclusion, they point out the ultimate risks of administering a β blocker to non-cardiac perioperative patients. "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 β blocker regimen has benefit without substantial harm. Patients are unlikely to accept the risk associated with perioperative extended-release metoprolol. "

Dr Lee A Fleisher, University of Pennsylvania School of Medicine, Philadelphia, PA, USA, and Dr Don Poldermans, Erasmus Medical Centre, Rotterdam, Netherlands, contributed an accompanying comment in which they agreed that the POIST study clearly indicates against the acute administration of higher dose β blocker therapy in the perioperative period, as it has greater risk than benefit. However, they additionally note the potential implications the study might have on daily clinical case, which can be made individual to the patient.

Also, they describe other protocols using a low dose β blocker therapy regimen, which have an established beneficial effect on postoperative outcome without an increased incidence of stroke. They recommend, finally, low dose use of β blockers in the perioperative period, while being supervised by clinicians experienced in hemodynamic care in surgery.

Effects of extended-release metoprolol succinate in patients undergoing non-cardiac surgery (POISE trial): a randomised controlled trial
POISE Study Group
The Lancet Online May 13, 2008
DOI:10.1016/S0140-6736(08)60601-7
Click Here For Abstract

Perioperative β blockade: where do we go from here?
Lee A Fleisher, Don Poldermans
The Lancet online May 13, 2008
DOI:10.1016/S0140-6736(08)60662-5
Click Here For Journal

Written by Anna Sophia McKenney
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