Level 1: Likely reliable evidence
Perioperative beta blockers have been promoted to reduce the risk for perioperative MI. However, while high-dose perioperative extended-release metoprolol succinate (Toprol XL) for noncardiac surgery decreased MI in high-risk patients, it increased mortality, based on the Perioperative Ischemic Evaluation (POISE) randomized trial of 9,298 patients (mean age 69 years) (Lancet. 2008;371:1839-1847). The inclusion criteria for the trial were age older than 45 years; not taking a beta blocker or planning to start a beta blocker; not taking verapamil; presence of atherosclerotic disease or any three of seven risk criteria (intrathoracic or intraperitoneal surgery, history of congestive heart failure, history of transient ischemic attack, diabetes, serum creatinine >1.97 mg/dL [175 µmol/L], age >70 years, emergent or urgent surgery).
The dosing regimen consisted of extended-release metoprolol 100 mg orally two to four hours preoperatively, then 100 mg orally six hours after surgery, increased to 200 mg orally 12 hours after surgery and continued daily for 30 days. Metoprolol was withheld or delayed any time the heart rate was <50 beats per minute or systolic BP was <100 mm Hg. IV infusion was used for patients unable to take oral medications.
Some patients (N=947, 10.2%) were excluded because of fraudulent data. When fraudulent data were found, all data from that hospital were excluded; investigators were still blinded to hospital and overall trial results. The intention-to-treat analysis included 8,351 patients; 8,331 (99.8%) completed follow-up at 30 days. Comparing metoprolol vs. placebo in intention-to-treat analysis, metoprolol was associated with increased mortality (3.1% vs. 2.3%, P=.0317, NNH 125) and an increased incidence of stroke (1% vs. 0.5%, P=.0053, NNH 200). Metoprolol was associated with a decreased rate of MI (4.2% vs. 5.7%, P=.0017, NNT 67) and cardiac revascularization (0.3% vs. 0.6%, P=.012, NNT 334). Post-hoc multivariate analyses suggest that hypotension (NNH 18), bradycardia (NNH 23), and stroke (NNH 200) may explain the increased risk of death associated with metoprolol in this trial.