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.).
RCT Entities:
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: K Leslie; D McIlroy; J Kasza; A Forbes; A Kurz; J Khan; C S Meyhoff; R Allard; G Landoni; X Jara; G Lurati Buse; K Candiotti; H-S Lee; R Gupta; T VanHelder; W Purayil; S De Hert; T Treschan; P J Devereaux Journal: Br J Anaesth Date: 2015-07-25 Impact factor: 9.166
Authors: Danielle Menosi Gualandro; Pai Ching Yu; Bruno Caramelli; André Coelho Marques; Daniela Calderaro; Luciana Savoy Fornari; Claudio Pinho; Alina Coutinho Rodrigues Feitosa; Carisi Anne Polanczyk; Carlos Eduardo Rochitte; Carlos Jardim; Carolina L Z Vieira; Debora Y M Nakamura; Denise Iezzi; Dirk Schreen; Eduardo Leal Adam; Elbio Antonio D'Amico; Emerson Q de Lima; Emmanuel de Almeida Burdmann; Enrique Indalecio Pachón Mateo; Fabiana Goulart Marcondes Braga; Fabio S Machado; Flavio J de Paula; Gabriel Assis Lopes do Carmo; Gilson Soares Feitosa-Filho; Gustavo Faibischew Prado; Heno Ferreira Lopes; João R C Fernandes; José J G de Lima; Luciana Sacilotto; Luciano Ferreira Drager; Luciano Janussi Vacanti; Luis Eduardo Paim Rohde; Luis F L Prada; Luis Henrique Wolff Gowdak; Marcelo Luiz Campos Vieira; Maristela Camargo Monachini; Milena Frota Macatrão-Costa; Milena Ribeiro Paixão; Mucio Tavares de Oliveira; Patricia Cury; Paula R Villaça; Pedro Silvio Farsky; Rinaldo F Siciliano; Roberto Henrique Heinisch; Rogerio Souza; Sandra F M Gualandro; Tarso Augusto Duenhas Accorsi; Wilson Mathias Journal: Arq Bras Cardiol Date: 2017 Jan-Feb Impact factor: 2.000