title: Effects of extended-release metoprolol succinate in patients undergoing non-cardiac surgery (POISE trial): a randomised controlled trial.
abstract: BACKGROUND
  Trials of beta blockers in patients undergoing non-cardiac surgery have reported conflicting results. This randomised controlled trial, done in 190 hospitals in 23 countries, was designed to investigate the effects of perioperative beta blockers.
  
  
  METHODS
  We randomly assigned 8351 patients with, or at risk of, atherosclerotic disease who were undergoing non-cardiac surgery to receive extended-release metoprolol succinate (n=4174) or placebo (n=4177), by a computerised randomisation phone service. Study treatment was started 2-4 h before surgery and continued for 30 days. Patients, health-care providers, data collectors, and outcome adjudicators were masked to treatment allocation. The primary endpoint was a composite of cardiovascular death, non-fatal myocardial infarction, and non-fatal cardiac arrest. Analyses were by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT00182039.
  
  
  RESULTS
  All 8351 patients were included in analyses; 8331 (99.8%) patients completed the 30-day follow-up. 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). Fewer patients in the metoprolol group than in the placebo group had a myocardial infarction (176 [4.2%] vs 239 [5.7%] patients; 0.73, 0.60-0.89; p=0.0017). However, there were more deaths in the metoprolol group than in the placebo group (129 [3.1%] vs 97 [2.3%] patients; 1.33, 1.03-1.74; p=0.0317). More patients in the metoprolol group than in the placebo group had a stroke (41 [1.0%] vs 19 [0.5%] patients; 2.17, 1.26-3.74; p=0.0053).
  
  
  CONCLUSIONS
  Our results highlight the risk in assuming a perioperative beta-blocker regimen has benefit without substantial harm, and the importance and need for large randomised trials in the perioperative setting. Patients are unlikely to accept the risks associated with perioperative extended-release metoprolol.
authors.affiliation: McMaster University, Faculty of Health Sciences, Clinical Epidemiology and Biostatistics, Room 2C8, 1200 Main Street West, Hamilton, ON, L8N 3Z5, Canada. philipj@mcmaster.ca
authors.forename: P J
authors.initials: PJ
authors.lastname: Devereaux
authors.forename: Homer
authors.initials: H
authors.lastname: Yang
authors.forename: Salim
authors.initials: S
authors.lastname: Yusuf
authors.forename: Gordon
authors.initials: G
authors.lastname: Guyatt
authors.forename: Kate
authors.initials: K
authors.lastname: Leslie
authors.forename: Juan Carlos
authors.initials: JC
authors.lastname: Villar
authors.forename: Denis
authors.initials: D
authors.lastname: Xavier
authors.forename: Susan
authors.initials: S
authors.lastname: Chrolavicius
authors.forename: Launi
authors.initials: L
authors.lastname: Greenspan
authors.forename: Janice
authors.initials: J
authors.lastname: Pogue
authors.forename: Prem
authors.initials: P
authors.lastname: Pais
authors.forename: Lisheng
authors.initials: L
authors.lastname: Liu
authors.forename: Shouchun
authors.initials: S
authors.lastname: Xu
authors.forename: German
authors.initials: G
authors.lastname: Málaga
authors.forename: Alvaro
authors.initials: A
authors.lastname: Avezum
authors.forename: Matthew
authors.initials: M
authors.lastname: Chan
authors.forename: Victor M
authors.initials: VM
authors.lastname: Montori
authors.forename: Mike
authors.initials: M
authors.lastname: Jacka
authors.forename: Peter
authors.initials: P
authors.lastname: Choi
mesh_terms: D000319:Adrenergic beta-Antagonists / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D000368:Aged; D001794:Blood Pressure / Q000187:drug effects; D002318:Cardiovascular Diseases / Q000401:mortality / Q000517:prevention & control*; D003692:Delayed-Action Preparations; D005260:Female; D006801:Humans; D007431:Intraoperative Complications / Q000517:prevention & control*; D008297:Male; D008790:Metoprolol / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D008875:Middle Aged; D019990:Perioperative Care / Q000379:methods*; D011300:Preoperative Care / Q000379:methods*; D012307:Risk Factors
chemical_list: D000319:Adrenergic beta-Antagonists; D003692:Delayed-Action Preparations; D008790:Metoprolol