"Although use of metoprolol in the perioperative setting may prevent myocardial infarction, this practice increases the risk of both stroke and death, according to the results of the PeriOperative Ischemic Evaluation (POISE) trial.
Surgery typically causes a rise in catecholamine levels, resulting in elevations in heart rate, blood pressure, and free fatty acid levels. All of these changes increase myocardial oxygen demand, according to the May 12 early online report from
The Lancet.Beta-blockers reduce the effects of catecholamines and, therefore in theory, should have a beneficial effect in surgical patients. Small and moderate-sized trials investigating the effects of these agents, however, have yielded conflicting results, Dr. P. J. Devereaux, from McMaster University in Hamilton, Ontario, Canada, and colleagues note.
The POISE study involved 8351 patients at risk for or with atherosclerotic disease who were randomized to receive extended-release metoprolol or placebo starting two to four hours prior to non-cardiac surgery and continuing for 30 days. The main outcome measure was a composite of cardiovascular death, non-fatal MI, and non-fatal cardiac arrest.
The rate of the main outcome in the metoprolol group was significantly lower than that in the placebo group: 5.8 vs. 6.9 per cent (p = 0.0399). Moreover, the percentage of patients who experienced an MI was lower in the metoprolol group: 4.2 vs. 5.7 per cent (p = 0.0017).
Further analysis, however, revealed that 3.1 per cent of metoprolol-treated patients died compared with just 2.3 per cent of controls (p = 0.0317). Similarly, the stroke rate in the metoprolol group, 1.0 per cent, was double that seen in the control group, 0.5 per cent (p = 0.0053).
"Our results highlight 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 perioperative setting," the authors conclude.
Editorialists Dr. Lee A. Fleisher, from the University of Pennsylvania in Philadelphia, and Dr. Don Poldermans, from Erasmus Medical Centre in Rotterdam, the Netherlands, comment: "The current trial clearly shows that acute administration of higher dose beta-blocker therapy in the perioperative period is associated with greater risk than benefit, but we believe that the protocol used in the Dutch Echocardiographic Cardiac Risk Evaluation Applying Stress Echo (DECREASE) studies (low-dose, long-acting agents titrated to effect at least seven days in advance) is associated with overall benefit compared to risk."
