Ko Dennis T, Krumholz Harlan M, Tu Jack V, Austin Peter C, Stukel Therese A, Koh Maria, Chong Alice, de Melo Jose Francisco, Jackevicius Cynthia A
From the Schulich Heart Centre, Sunnybrook Health Sciences Centre (D.T.K., J.V.T.) and Institute of Health Policy, Management and Evaluation (D.T.K., J.V.T., P.C.A., T.A.S., C.A.J.), University of Toronto, Canada; Institute for Clinical Evaluative Sciences, Toronto, Canada (D.T.K., J.V.T., P.C.A., T.A.S., M.K., A.C., J.F.d.M., C.A.J.); Department of Medicine, Section of Cardiovascular Medicine, Yale University School of Medicine, New Haven, CT (H.M.K.); Center for Outcomes Research and Evaluation, Yale New Haven Hospital, CT (H.M.K.); Department of Health Policy and Management, Yale School of Public Health (H.M.K); Department of Pharmacy Practice and Administration, College of Pharmacy, Western University of Health Sciences, Pomona, CA (C.A.J.); Veterans Affairs Greater Los Angeles Healthcare System, CA (C.A.J.); and University Health Network, Toronto, Canada (C.A.J.).
Circ Cardiovasc Qual Outcomes. 2018 Mar;11(3):e004194. doi: 10.1161/CIRCOUTCOMES.117.004194.
Clopidogrel is one of the most commonly prescribed medications because of its ability to improve clinical outcomes for a broad range of cardiovascular conditions. After patent protection expired for Plavix in 2012, many healthcare systems adopted generic clopidogrel as a strategy to reduce healthcare costs.
We conducted a population-based observational study to determine whether generic clopidogrel was noninferior to Plavix. Patients who were hospitalized with an acute coronary syndrome (ACS) from 2009 to 2014 in Ontario, Canada, >65 years, survived ≥7 days after discharge, were eligible for inclusion. The primary outcome was a composite of death and recurrent ACS at 1 year. The noninferiority margin was prespecified at a relative hazard difference of 10%. Inverse propensity of treatment weighting of the propensity score was used to account for differences in baseline characteristics between the treatment groups. The effect of clopidogrel on the hazard of clinical outcomes was estimated using a Cox proportional hazards model within the propensity-weighted cohort using Plavix as a reference. Our study included 24 530 patients with ACS, 12 643 were prescribed Plavix and 11 887 were prescribed generic clopidogrel at hospital discharge. The mean age was 77 years, 57% were men, and 21% had an ST-segment-elevation myocardial infarction. At 1 year, 17.6% of patients prescribed Plavix and 17.9% of patients prescribed clopidogrel experienced the primary outcome (hazard ratio, 1.02; 95% confidence interval, 0.96-1.08; =0.005 for noninferiority). No significant differences between rates of death, all-cause readmission, ACS, stroke or transient ischemic attack, or bleeding were observed.
Generic clopidogrel was noninferior to Plavix with respect to the composite end point of death and recurrent hospitalization for ACS at 1 year among adults >65 years after an ACS hospitalization. Our findings support generic clopidogrel in ACS, which could lead to substantial healthcare cost savings.
氯吡格雷因其能够改善多种心血管疾病的临床结局，是最常用的处方药之一。2012年波立维的专利保护到期后，许多医疗保健系统采用氯吡格雷仿制药作为降低医疗成本的策略。
我们进行了一项基于人群的观察性研究，以确定氯吡格雷仿制药是否不劣于波立维。2009年至2014年在加拿大安大略省因急性冠状动脉综合征（ACS）住院、年龄>65岁、出院后存活≥7天的患者符合纳入条件。主要结局是1年时死亡和复发性ACS的复合结局。非劣效性界值预先设定为相对风险差异10%。采用倾向评分的逆倾向治疗加权法来解释治疗组之间基线特征的差异。在倾向加权队列中，以波立维为参照，使用Cox比例风险模型估计氯吡格雷对临床结局风险的影响。我们的研究纳入了24530例ACS患者，出院时12643例患者服用波立维，11887例患者服用氯吡格雷仿制药。平均年龄为77岁，57%为男性，21%发生ST段抬高型心肌梗死。1年时，服用波立维的患者中有17.6%，服用氯吡格雷的患者中有17.9%发生主要结局（风险比，1.02；95%置信区间，0.96 - 1.08；非劣效性P = 0.005）。在死亡率、全因再入院率、ACS、中风或短暂性脑缺血发作或出血率方面未观察到显著差异。
在65岁以上成年人ACS住院后1年，氯吡格雷仿制药在死亡和ACS复发性住院的复合终点方面不劣于波立维。我们的研究结果支持在ACS中使用氯吡格雷仿制药，这可能会大幅节省医疗成本。
