非心脏手术患者中阿司匹林与安慰剂、可乐定与安慰剂的两因素随机临床试验一年结果。
One-year Results of a Factorial Randomized Trial of Aspirin versus Placebo and Clonidine versus Placebo in Patients Having Noncardiac Surgery.
机构信息
From the Department of Outcomes Research, Anesthesiology Institute, Cleveland Clinic, Cleveland, Ohio (D.I.S., A.K., A.T.) Population Health Research Institute (D.I.S., D.C., S.Y., Y.L.M., A.L., K.B., S.P., P.J.D.) Department of Medicine (D.C., S.Y., G.G., P.J.D.) Department of Health Research Methods, Evidence, and Impact (D.C., S.Y., G.G., Y.L.M., A.L., P.J.D.) Faculty of Health Sciences, Department of Anesthesia (Y.L.M.) Department of Surgery (R.W., A.L.), McMaster University, Hamilton, Ontario, Canada Department of Anaesthesia and Pain Management, Royal Melbourne Hospital and Centre for Integrated Critical Care, University of Melbourne, Melbourne, Australia (K.L.) Public Health and Clinical Epidemiology-Iberoamerican Cochrane Centre, Barcelona, Spain (E.P.) University of Alberta and Mazankowski Alberta Heart Institute, Edmonton, Alberta, Canada (M.G.) Department of Research, Foundation for Pediatric Cardiology, Institute of Cardiology and Faculty of Health Sciences (Departamento de Investigaciones, Fundación Cardioinfantil-Instituto de Cardiología and Facultad de Ciencias de la Salud), Universidad Autónoma de Bucaramanga, Colombia (J.C.V.) University of Western Ontario, London, Ontario, Canada (M.M.) Department of Clinical Research, Narayana Hrudayalaya Limited, Bangalore, India (A.S.) University of Cape Town and Groote Schuur Hospital, Cape Town, South Africa (B.M.B.) Department of Anaesthesia and Intensive Care, Bispebjerg and Frederiksberg Hospital, University of Copenhagen, Copenhagen, Denmark (C.S.M.) Department of Anesthesiology and Perioperative Medicine, Kingston Health Sciences Centre and Queen's University, Kingston, Canada (J.L.P., I.G.) St. John's Medical College and Research Institute, Bangalore, Karnataka, India (D.X.) Department of Anaesthesia and Intensive Care, The Chinese University of Hong Kong, Hong Kong (M.T.V.C.) University of North Carolina School of Medicine, Chapel Hills, North Carolina (P.A.K.) NHS Grampian and the University of Aberdeen, Aberdeen, United Kingdom (P.F.) Knowledge and Evidence Unite (Unidad de Conocimiento y Evidencia), Universidad Peruana Cayetano Heredia, Lima, Peru (G.M.) Department of Anaesthesia, Intensive Care, and Pain Medicine, Medical University of Vienna, Vienna, Austria (E.F.) Shifa International Hospitals, Islamabad, Pakistan (M.A.) University of the Andes and Santa Maria Clinic (Universidad de Los Andes and Clinica Santa María), Santiago, Chile (D.T.) Department of Anesthesiology, University of Malaya, Kuala Lumpur, Malaysia (C.Y.W.) Biomedical Research Institute (IIB - Sant Pau), Barcelona, Spain (P.P.) Hospital Israelita Albert Einstein, São Paulo, Brazil (O.B.) Department of Surgery, University of Manitoba, Winnipeg, Manitoba, Canada (S.S.) Department of Anesthesia and Intensive Care, IRCCS San Raffaele Scientific Institute and Vita-Salute University, Milan, Italy (G.L.).
出版信息
Anesthesiology. 2020 Apr;132(4):692-701. doi: 10.1097/ALN.0000000000003158.
BACKGROUND
The authors previously reported that perioperative aspirin and/or clonidine does not prevent a composite of death or myocardial infarction 30 days after noncardiac surgery. Moreover, aspirin increased the risk of major bleeding and clonidine caused hypotension and bradycardia. Whether these complications produce harm at 1 yr remains unknown.
METHODS
The authors randomized 10,010 patients with or at risk of atherosclerosis and scheduled for noncardiac surgery in a 1:1:1:1 ratio to clonidine/aspirin, clonidine/aspirin placebo, clonidine placebo/aspirin, or clonidine placebo/aspirin placebo. Patients started taking aspirin or placebo just before surgery; those not previously taking aspirin continued daily for 30 days, and those taking aspirin previously continued for 7 days. Patients were also randomly assigned to receive clonidine or placebo just before surgery, with the study drug continued for 72 h.
RESULTS
Neither aspirin nor clonidine had a significant effect on the primary 1-yr outcome, a composite of death or nonfatal myocardial infarction, with a 1-yr hazard ratio for aspirin of 1.00 (95% CI, 0.89 to 1.12; P = 0.948; 586 patients [11.8%] vs. 589 patients [11.8%]) and a hazard ratio for clonidine of 1.07 (95% CI, 0.96 to 1.20; P = 0.218; 608 patients [12.1%] vs. 567 patients [11.3%]), with effect on death or nonfatal infarction. Reduction in death and nonfatal myocardial infarction from aspirin in patients who previously had percutaneous coronary intervention at 30 days persisted at 1 yr. Specifically, the hazard ratio was 0.58 (95% CI, 0.35 to 0.95) in those with previous percutaneous coronary intervention and 1.03 (95% CI, 0.91to 1.16) in those without (interaction P = 0.033). There was no significant effect of either drug on death, cardiovascular complications, cancer, or chronic incisional pain at 1 yr (all P > 0.1).
CONCLUSIONS
Neither perioperative aspirin nor clonidine have significant long-term effects after noncardiac surgery. Perioperative aspirin in patients with previous percutaneous coronary intervention showed persistent benefit at 1 yr, a plausible sub-group effect.
背景
作者先前报告称，围手术期使用阿司匹林和/或可乐定不能预防非心脏手术后 30 天内死亡或心肌梗死的复合事件。此外，阿司匹林增加了大出血的风险，可乐定导致低血压和心动过缓。这些并发症在 1 年内是否会造成危害尚不清楚。
方法
作者以 1:1:1:1 的比例将 10010 例患有或有动脉粥样硬化风险且计划接受非心脏手术的患者随机分为可乐定/阿司匹林组、可乐定/阿司匹林安慰剂组、可乐定安慰剂/阿司匹林组或可乐定安慰剂/阿司匹林安慰剂组。患者在手术前开始服用阿司匹林或安慰剂；未服用阿司匹林的患者持续服用 30 天，之前服用阿司匹林的患者持续服用 7 天。患者还被随机分配在手术前接受可乐定或安慰剂治疗，研究药物持续 72 小时。
结果
阿司匹林和可乐定均未对主要的 1 年结局（死亡或非致死性心肌梗死的复合事件）产生显著影响，阿司匹林的 1 年风险比为 1.00（95%CI，0.89 至 1.12；P=0.948；586 例患者[11.8%]与 589 例患者[11.8%]），可乐定的风险比为 1.07（95%CI，0.96 至 1.20；P=0.218；608 例患者[12.1%]与 567 例患者[11.3%]），对死亡或非致死性梗死均无影响。阿司匹林在 30 天时已行经皮冠状动脉介入治疗的患者中降低死亡和非致死性心肌梗死的效果持续到 1 年。具体而言，在有既往经皮冠状动脉介入治疗的患者中，风险比为 0.58（95%CI，0.35 至 0.95），在无既往经皮冠状动脉介入治疗的患者中为 1.03（95%CI，0.91 至 1.16）（交互 P=0.033）。两种药物在 1 年时对死亡、心血管并发症、癌症或慢性切口疼痛均无显著影响（均 P>0.1）。
结论
非心脏手术后，围手术期使用阿司匹林和可乐定均无明显的长期影响。在既往行经皮冠状动脉介入治疗的患者中，围手术期使用阿司匹林可在 1 年内持续获益，这可能是一个亚组效应。
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