title: Clonidine in patients undergoing noncardiac surgery.
abstract: BACKGROUND
  Marked activation of the sympathetic nervous system occurs during and after noncardiac surgery. Low-dose clonidine, which blunts central sympathetic outflow, may prevent perioperative myocardial infarction and death without inducing hemodynamic instability.
  
  
  METHODS
  We performed a blinded, randomized trial with a 2-by-2 factorial design to allow separate evaluation of low-dose clonidine versus placebo and low-dose aspirin versus placebo in patients with, or at risk for, atherosclerotic disease who were undergoing noncardiac surgery. A total of 10,010 patients at 135 centers in 23 countries were enrolled. For the comparison of clonidine with placebo, patients were randomly assigned to receive clonidine (0.2 mg per day) or placebo just before surgery, with the study drug continued until 72 hours after surgery. The primary outcome was a composite of death or nonfatal myocardial infarction at 30 days.
  
  
  RESULTS
  Clonidine, as compared with placebo, did not reduce the number of primary-outcome events (367 and 339, respectively; hazard ratio with clonidine, 1.08; 95% confidence interval [CI], 0.93 to 1.26; P=0.29). Myocardial infarction occurred in 329 patients (6.6%) assigned to clonidine and in 295 patients (5.9%) assigned to placebo (hazard ratio, 1.11; 95% CI, 0.95 to 1.30; P=0.18). Significantly more patients in the clonidine group than in the placebo group had clinically important hypotension (2385 patients [47.6%] vs. 1854 patients [37.1%]; hazard ratio 1.32; 95% CI, 1.24 to 1.40; P<0.001). Clonidine, as compared with placebo, was associated with an increased rate of nonfatal cardiac arrest (0.3% [16 patients] vs. 0.1% [5 patients]; hazard ratio, 3.20; 95% CI, 1.17 to 8.73; P=0.02).
  
  
  CONCLUSIONS
  Administration of low-dose clonidine in patients undergoing noncardiac surgery did not reduce the rate of the composite outcome of death or nonfatal myocardial infarction; it did, however, increase the risk of clinically important hypotension and nonfatal cardiac arrest. (Funded by the Canadian Institutes of Health Research and others; POISE-2 ClinicalTrials.gov number, NCT01082874.).
authors.affiliation: The authors' affiliations are listed in the Appendix.
authors.forename: P J
authors.initials: PJ
authors.lastname: Devereaux
authors.forename: Daniel I
authors.initials: DI
authors.lastname: Sessler
authors.forename: Kate
authors.initials: K
authors.lastname: Leslie
authors.forename: Andrea
authors.initials: A
authors.lastname: Kurz
authors.forename: Marko
authors.initials: M
authors.lastname: Mrkobrada
authors.forename: Pablo
authors.initials: P
authors.lastname: Alonso-Coello
authors.forename: Juan Carlos
authors.initials: JC
authors.lastname: Villar
authors.forename: Alben
authors.initials: A
authors.lastname: Sigamani
authors.forename: Bruce M
authors.initials: BM
authors.lastname: Biccard
authors.forename: Christian S
authors.initials: CS
authors.lastname: Meyhoff
authors.forename: Joel L
authors.initials: JL
authors.lastname: Parlow
authors.forename: Gordon
authors.initials: G
authors.lastname: Guyatt
authors.forename: Andrea
authors.initials: A
authors.lastname: Robinson
authors.forename: Amit X
authors.initials: AX
authors.lastname: Garg
authors.forename: Reitze N
authors.initials: RN
authors.lastname: Rodseth
authors.forename: Fernando
authors.initials: F
authors.lastname: Botto
authors.forename: Giovanna
authors.initials: G
authors.lastname: Lurati Buse
authors.forename: Denis
authors.initials: D
authors.lastname: Xavier
authors.forename: Matthew T V
authors.initials: MT
authors.lastname: Chan
authors.forename: Maria
authors.initials: M
authors.lastname: Tiboni
authors.forename: Deborah
authors.initials: D
authors.lastname: Cook
authors.forename: Priya A
authors.initials: PA
authors.lastname: Kumar
authors.forename: Patrice
authors.initials: P
authors.lastname: Forget
authors.forename: German
authors.initials: G
authors.lastname: Malaga
authors.forename: Edith
authors.initials: E
authors.lastname: Fleischmann
authors.forename: Mohammed
authors.initials: M
authors.lastname: Amir
authors.forename: John
authors.initials: J
authors.lastname: Eikelboom
authors.forename: Richard
authors.initials: R
authors.lastname: Mizera
authors.forename: David
authors.initials: D
authors.lastname: Torres
authors.forename: C Y
authors.initials: CY
authors.lastname: Wang
authors.forename: Tomas
authors.initials: T
authors.lastname: Vanhelder
authors.forename: Pilar
authors.initials: P
authors.lastname: Paniagua
authors.forename: Otavio
authors.initials: O
authors.lastname: Berwanger
authors.forename: Sadeesh
authors.initials: S
authors.lastname: Srinathan
authors.forename: Michelle
authors.initials: M
authors.lastname: Graham
authors.forename: Laura
authors.initials: L
authors.lastname: Pasin
authors.forename: Yannick
authors.initials: Y
authors.lastname: Le Manach
authors.forename: Peggy
authors.initials: P
authors.lastname: Gao
authors.forename: Janice
authors.initials: J
authors.lastname: Pogue
authors.forename: Richard
authors.initials: R
authors.lastname: Whitlock
authors.forename: André
authors.initials: A
authors.lastname: Lamy
authors.forename: Clive
authors.initials: C
authors.lastname: Kearon
authors.forename: Clara
authors.initials: C
authors.lastname: Chow
authors.forename: Shirley
authors.initials: S
authors.lastname: Pettit
authors.forename: Susan
authors.initials: S
authors.lastname: Chrolavicius
authors.forename: Salim
authors.initials: S
authors.lastname: Yusuf
mesh_terms: D058647:Adrenergic alpha-2 Receptor Agonists / Q000009:adverse effects / Q000627:therapeutic use*; D000368:Aged; D003000:Clonidine / Q000009:adverse effects / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D007022:Hypotension / Q000139:chemically induced*; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000517:prevention & control*; D019990:Perioperative Care; D011183:Postoperative Complications / Q000139:chemically induced / Q000517:prevention & control*; D013514:Surgical Procedures, Operative / Q000401:mortality*; D017211:Treatment Failure
chemical_list: D058647:Adrenergic alpha-2 Receptor Agonists; D003000:Clonidine