POISE Trial: Perioperative Metoprolol Reduces MI but Increases Stroke & Mortality [Classics Series]

1. In adults undergoing noncardiac surgery, perioperative β-blocker therapy with extended-release metoprolol significantly reduced nonfatal myocardial infarction (MI) risk but increased stroke and all-cause mortality at 30 days.

2. The landmark POISE trial underscores the need to weigh cardioprotective benefits against heightened neurologic and mortality risks when starting perioperative β-blockers.

Original Date of Publication: May 31, 2008

Study Rundown: The PeriOperative ISchemic Evaluation (POISE) trial, published in The Lancet, was a large, double-blind, multicenter randomized controlled trial assessing perioperative metoprolol succinate in patients aged ≥45 years at elevated cardiovascular risk undergoing noncardiac surgery. Conducted at 190 hospitals in 23 countries, it enrolled 8,351 participants randomized to extended-release metoprolol or placebo, initiated 2–4 hours before surgery and continued for 30 days.

The primary composite outcome—cardiovascular death, nonfatal myocardial infarction, or nonfatal cardiac arrest—was lower in the metoprolol group, driven primarily by reduced nonfatal MI. However, stroke incidence was more than doubled and overall mortality increased. Adverse events contributing to these risks included hypotension (15.0% vs. 9.7%; HR 1.55) and bradycardia (6.6% vs. 2.4%; HR 2.74), both of which were strongly associated with stroke and death. These findings shifted clinical practice guidelines, emphasizing careful patient selection and hemodynamic monitoring. Follow-up research, including POISE-2 and the VISION study, continues to explore safer strategies for perioperative cardiovascular protection.

Click to read the study in The Lancet

Lead Study Investigator, Dr. P.J. Devereaux, MD, PhD, FRCPC, talks to 2 Minute Medicine: McMaster University, Department of Clinical Epidemiology and Biostatistics, Associate Professor.

“There is little doubt that initiating a beta-blocker anytime prior to noncardiac surgery has benefit (i.e., it prevents perioperative myocardial infarction). It is also important to recognize the risk related to perioperative beta-blockers (i.e., an increased risk of stroke and death). These complications appear to primarily occur through hypotension on surgical floors. I believe the take away messages from POISE are that controlling the sympathetic system in the perioperative period has benefit, but we need to find a way to do it safely. There is the potential that other drugs (e.g., clonidine) or other processes (e.g., more intense monitoring of hemodynamics on surgical floors) may achieve this goal. A final lesson learned from POISE is that we need large trials to establish actual effects.”

In-Depth [randomized controlled study]: The final analysis involved 8,351 patients from 190 hospitals in 23 countries randomized to either perioperative treatment with extended-release metoprolol or placebo. Patients were eligible for the trial if they were ≥45 years, were undergoing non-cardiac surgery, had expected hospitalization ≥24 hours, and had elevated risk of perioperative cardiac events (e.g., history of coronary artery disease, stroke, hospitalization for congestive heart failure, undergoing major vascular surgery). Exclusion criteria included heart rate <50 beats per minute, second/third-degree heart block, asthma, treatment with a beta-blocker, and prior adverse reaction to beta-blocker. The primary outcome was a composite of cardiovascular death, non-fatal myocardial infarction, and non-fatal cardiac arrest at 30 days.

Beta-blockers were found to significantly reduce the incidence of the primary endpoint compared to placebo (HR 0.84; 95%CI 0.70-0.99), due to a significant reduction in myocardial infarctions (HR 0.73; 95%CI 0.60-0.89). Compared to placebo, perioperative beta-blockade was also found to significantly increase the risk of stroke (HR 2.17; 95%CI 1.26-3.74), clinically significant hypotension (HR 1.55; 95%CI 1.38-1.74), and clinically significant bradycardia (HR 2.74; 95%CI 2.19-3.43). Furthermore, the metoprolol group had a significantly higher risk of mortality (HR 1.33; 95%CI 1.03-1.74).

Image: PD

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