What is the clinical evidence from this study?

Study design: Review. Population: Noncardiac surgery in patients with or at risk of atherosclerotic disease (n=8351). Intervention: Extended-release metoprolol succinate vs. Placebo. Primary outcome: 30-day composite of cardiovascular death, nonfatal MI, or nonfatal cardiac arrest (HR 0.84, 95% CI 0.70-0.99, p=0.0399).

October 30, 2009Cleveland Clinic Journal of Medicine31 citations

The experts debate: Perioperative beta-blockade for noncardiac surgery—proven safe or not?

DPDon Poldermans PDP.J. Devereaux

Key Result

Extended-release metoprolol succinate reduced the 30-day composite of cardiovascular death, nonfatal MI, or nonfatal cardiac arrest by 16% (HR 0.84) compared to placebo in patients undergoing noncardiac surgery, but significantly increased total mortality and stroke.

Structured PICO

Does perioperative beta-blockade improve cardiovascular outcomes and mortality in patients undergoing noncardiac surgery?

Population

8,351 patients aged 45 years or older with or at risk of atherosclerotic disease undergoing noncardiac surgery, followed for 30 days.

Intervention

Perioperative beta-blockade (e.g., extended-release metoprolol succinate, bisoprolol, atenolol) initiated prior to surgery.

Comparator

Placebo or standard perioperative care.

Outcome

Composite of cardiovascular death, nonfatal MI, or nonfatal cardiac arrest at 30 days (POISE primary endpoint).composite

Perioperative beta-blockade reduces nonfatal myocardial infarction but may significantly increase the risk of stroke and mortality if initiated acutely at high doses before noncardiac surgery, challenging routine prophylactic use.

Main Result

Hazard Ratio: 0.84 (95% CI 0.7–0.99)

Absolute Event Rate: 5.8% vs 6.9%

p-value: p=0.0399

Limitations

High starting dose of metoprolol without adequate time for preoperative titration may have contributed to adverse outcomes
Exclusion of patients on chronic beta-blocker therapy limits applicability to that subgroup
Clinically significant hypotension was common and served as a dominant predictor of both death and stroke
POISE used a high starting dose of metoprolol (100 mg) immediately prior to surgery without adequate time for titration.
Data fraud at some centers in the POISE trial required the exclusion of 947 patients.
Earlier small trials supporting beta-blockade had methodological limitations, including being unblinded, stopped early, or failing to follow intention-to-treat principles.

Abstract

Guidelines on perioperative management of patients undergoing noncardiac surgery recommend the use of prophylactic perioperative beta-blockers in high-risk patients who are not already taking them, and their continuance in patients on chronic beta-blockade prior to surgery. These recommendations were challenged recently by results of the Perioperative Ischemic Evaluation (POISE), a large randomized trial of extended-release metoprolol succinate started immediately before noncardiac surgery in patients at high risk for atherosclerotic disease. While metoprolol significantly reduced myocardial infarctions relative to placebo in POISE, it also was associated with significant excesses of both stroke and mortality. The merits and limitations of POISE and its applicability in light of other trials of perioperative beta-blockade are debated here by two experts in the field-Dr. Don Poldermans and Dr. P. J. Devereaux (co-principal investigator of POISE).

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