What are the implications of the POISE (Perioperative Ischemic Evaluation) 1 trial on the use of beta-blockers, such as metoprolol (beta-blocker), in non-cardiac surgery?

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POISE-1 Trial Implications for Perioperative Beta-Blocker Use

The POISE-1 trial fundamentally changed perioperative beta-blocker practice by demonstrating that while metoprolol reduces nonfatal myocardial infarction, it significantly increases mortality, stroke, hypotension, and bradycardia when initiated shortly before non-cardiac surgery—a finding that led to major guideline revisions restricting beta-blocker initiation in beta-blocker-naïve patients. 1

Key POISE-1 Trial Findings

The POISE-1 trial enrolled 8,351 patients across 190 hospitals in 23 countries, making it the largest perioperative beta-blocker study to date. 1 The trial tested extended-release metoprolol succinate started 2-4 hours before surgery and continued for 30 days. 1

Primary Results Showed Mixed Outcomes:

  • Reduced nonfatal MI: 4.2% in metoprolol group vs 5.7% in placebo (HR 0.73, p=0.0017), preventing approximately 17 nonfatal MIs per 1000 patients treated 1, 2

  • Increased all-cause mortality: 3.1% in metoprolol group vs 2.3% in placebo (HR 1.33, p=0.0317), causing 6 excess deaths per 1000 patients treated 1, 2

  • Increased nonfatal stroke: 1.0% in metoprolol group vs 0.5% in placebo (HR 2.17, p=0.0053), causing 4 excess strokes per 1000 patients treated 1, 2

  • Increased hypotension and bradycardia: Both complications occurred significantly more frequently with metoprolol 1

Impact on Clinical Guidelines

The ACC/AHA systematically reviewed all perioperative beta-blocker evidence following POISE-1 and the controversial DECREASE trials. 2 Their 2014 analysis fundamentally reshaped recommendations:

Current Evidence-Based Recommendations:

Continue beta-blockers in patients already taking them: Withdrawal increases 1-year mortality dramatically (HR 2.7), and postoperative discontinuation carries 50% mortality versus 1.5% with continuation. 3, 4 The FDA label explicitly warns against abrupt discontinuation in patients with coronary artery disease, as severe exacerbation of angina, myocardial infarction, and ventricular arrhythmias have been reported. 4

Do NOT routinely initiate beta-blockers in beta-blocker-naïve patients, particularly within 1 day of surgery. 3, 2 The ACC/AHA systematic review confirmed that perioperative beta blockade started within 1 day or less before non-cardiac surgery prevents nonfatal MI but increases risks of stroke, death, hypotension, and bradycardia. 2

Critical Insights Beyond POISE-1

The Problem Was Not Unique to POISE-1's Protocol:

A common criticism suggested POISE-1's harms resulted from using high-dose, long-acting metoprolol started shortly before surgery. 2 However, the ACC/AHA systematic review found that other trials using different dosing regimens demonstrated consistent signals of increased stroke, hypotension, and bradycardia. 2 When POISE-1 was excluded from meta-analysis, the remaining studies still showed qualitatively similar increases in mortality (RR 1.17). 2

Timing Matters—But Data Are Limited:

Excluding the controversial DECREASE trials, there are insufficient data on beta blockade started 2 or more days prior to surgery. 2 All reliable RCTs aside from DECREASE initiated beta-blockers within 1 day or less before surgery. 2 This represents a critical knowledge gap, as earlier initiation with dose titration might theoretically reduce hemodynamic complications. 2

Risk Stratification for Beta-Blocker Decisions

High-Risk Patients May Benefit:

Observational data suggest patients with 3-4 cardiac risk factors (renal failure, coronary artery disease, diabetes mellitus, major body cavity surgery) had reduced mortality with beta-blockade (OR 0.63). 5 Patients with heart failure or heavy comorbidities may benefit from perioperative beta-blocker therapy. 6

Low-Risk Patients Are Harmed:

Patients with no cardiac risk factors had significantly higher mortality with beta-blockade (OR 1.19), and patients with uncomplicated hypertension may be at increased risk. 5, 6 This contradicts earlier broad recommendations for beta-blockers in patients with untreated hypertension or cardiac risk factors. 2

Mechanism of Harm

The increased mortality in POISE-1 was primarily driven by sepsis and infection deaths, which were more common in the metoprolol group. 2 The cohort that developed clinically significant hypotension had the largest population-attributable risk for death and stroke. 2 This suggests that excessive hemodynamic suppression—particularly hypotension—mediates the increased mortality and stroke risk. 2

Common Pitfalls to Avoid

Do not start beta-blockers on the day of surgery in beta-blocker-naïve patients, even those with cardiac risk factors, as the harm outweighs benefit. 2, 3

Do not abruptly discontinue beta-blockers perioperatively in patients already taking them—continue through the perioperative period and taper gradually over 1-2 weeks if discontinuation is necessary. 4

Monitor for hypotension and bradycardia aggressively in patients receiving perioperative beta-blockers, as these complications predict mortality and stroke. 2, 4

Do not assume cardioselectivity eliminates risk—even beta-1 selective agents like metoprolol increase stroke, hypotension, and bradycardia across multiple trials. 2

Practical Algorithm for Perioperative Beta-Blocker Management

For patients ALREADY on beta-blockers:

  • Continue without interruption through surgery and postoperatively 3, 4
  • Monitor heart rate and blood pressure closely 4
  • Have treatment available for bradycardia and hypotension 4

For beta-blocker-NAÏVE patients:

  • Do NOT initiate within 1 day of surgery 3, 2
  • Consider initiation only in very high-risk patients (3-4 cardiac risk factors) with adequate time for dose titration (ideally weeks before surgery, though data are limited) 5, 6
  • Accept that low-risk patients derive no benefit and face increased mortality 5

Intraoperative considerations:

  • The FDA label warns that chronically administered beta-blocking therapy should not be routinely withdrawn prior to major surgery, but the impaired ability of the heart to respond to reflex adrenergic stimuli may augment risks of general anesthesia and surgical procedures. 4
  • Have vasopressors and chronotropic agents readily available 4

References

2
Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

3
Guideline

Perioperative Cardiovascular Management

Praxis Medical Insights: Practical Summaries of Clinical Guidelines, 2025

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Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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