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document
Clonidine in patients undergoing noncardiac surgery . 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 . ) .
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Intervention_Pharmacological
Clonidine
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Intervention_Pharmacological
low-dose clonidine versus
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Intervention_Control
placebo
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Intervention_Pharmacological
and low-dose aspirin versus placebo
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Intervention_Pharmacological
clonidine with placebo
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Outcome_Physical
perioperative myocardial infarction
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Outcome_Mortality
death
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Outcome_Mortality
death
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Outcome_Physical
nonfatal myocardial infarction
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Outcome_Physical
primary-outcome events
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Outcome_Physical
Myocardial infarction
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Outcome_Physical
hypotension
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Outcome_Physical
nonfatal cardiac arrest
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Outcome_Mortality
death
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Outcome_Physical
nonfatal myocardial infarction
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Outcome_Physical
clinically important hypotension
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Outcome_Physical
nonfatal cardiac arrest
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Participant_Condition
patients undergoing noncardiac surgery .
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Participant_Condition
patients with , or at risk for , atherosclerotic disease who were undergoing noncardiac surgery .
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Participant_Condition
patients undergoing noncardiac surgery