POISE
Effects of extended-release metoprolol succinate in patients undergoing non-cardiac surgery
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Overview
Perioperative metoprolol reduced MI but increased stroke and death when started right before surgery.
Clinical takeaway
POISE is the perioperative beta-blocker cautionary trial: avoid reflexively starting high-dose beta blockers immediately before noncardiac surgery.
Key result
Metoprolol reduced MI (4.2% vs 5.7%) but increased stroke (1.0% vs 0.5%) and all-cause mortality (3.1% vs 2.3%).
Practice impact
Continue chronic beta blockers, but do not newly start high-dose beta blockers on the eve of surgery.
Evidence
Study design
Randomized, double-blind, placebo-controlled trial.
Enrollment
8,351
Follow-up
30 days.
Geography
Multinational
Clinical question
Does perioperative extended-release metoprolol reduce major cardiovascular events in patients undergoing noncardiac surgery?
Population
- Adults undergoing noncardiac surgery with or at risk for atherosclerotic disease.
Intervention
Extended-release metoprolol succinate started 2-4 hours before surgery and continued for 30 days.
Comparator
Placebo.
Primary outcome
Composite of cardiovascular death, nonfatal myocardial infarction, and nonfatal cardiac arrest.
Metoprolol reduced the primary ischemic composite but caused offsetting increases in stroke and death.
Hazard ratio / 0.84 / 95% CI 0.70-0.99 / p=0.0399
Key results
- Primary composite was reduced with metoprolol: 5.8% vs 6.9%; HR 0.84 (95% CI 0.70-0.99; p=0.0399).
- Myocardial infarction was reduced: 4.2% vs 5.7%; HR 0.73 (95% CI 0.60-0.89; p=0.0017).
- All-cause mortality was increased with metoprolol: 3.1% vs 2.3%; HR 1.33 (95% CI 1.03-1.74; p=0.0317).
- Stroke was increased with metoprolol: 1.0% vs 0.5%; HR 2.17 (95% CI 1.26-3.74; p=0.0053).
Harms
- Stroke was increased.
- All-cause mortality was increased.
- Clinically significant hypotension and bradycardia were more common.
Clinical Use
Practice impact
- Changed perioperative practice away from initiating high-dose beta blockers immediately before surgery.
Applicability
- Patients undergoing noncardiac surgery who are being considered for new perioperative beta blockade.
Limitations
- Tested a high-dose, rapid-start regimen; it does not answer careful outpatient initiation weeks before surgery.
- Does not argue against continuing chronic beta blockers.
Common misinterpretations
- Do not stop a patient's chronic beta blocker because of POISE; the key harm is acute high-dose initiation without time to titrate.
Citation
POISE Study Group, Devereaux PJ, Yang H, et al. Effects of extended-release metoprolol succinate in patients undergoing non-cardiac surgery (POISE trial): a randomised controlled trial. Lancet. 2008;371(9627):1839-1847. doi:10.1016/S0140-6736(08)60601-7
Fewer patients in the metoprolol group than in the placebo group reached the primary endpoint (244 [5.8%] patients in the metoprolol group vs 290 [6.9%] in the placebo group; hazard ratio 0.84, 95% CI 0.70-0.99; p=0.0399).
- PMID
- 18479744