Kutcher Stephen A, Dendukuri Nandini, Dandona Sonny, Nadeau Lyne, Brophy James M
Department of Epidemiology, Biostatistics and Occupational Health (Kutcher, Brophy), McGill University; Centre for Outcomes Research and Evaluation (Dendukuri, Nadeau, Brophy), McGill University Health Centre Research Institute; Department of Medicine (Dendukuri, Dandona, Brophy), McGill University, Montréal, Que.
CMAJ. 2025 Mar 30;197(12):E309-E318. doi: 10.1503/cmaj.241862.
Dual antiplatelet therapy is the standard of care for acute coronary syndrome, but uncertainty exists regarding the optimal regimen for patients in North America. We sought to compare the effectiveness and safety of acetylsalicylic acid (ASA) and ticagrelor or clopidogrel in patients with acute coronary syndrome from a single tertiary academic centre in Montréal, Canada.
We conducted a pragmatic, open-label, time-clustered (bimonthly between October 2018 and March 2021), randomized controlled trial. The primary effectiveness end point was a composite of all-cause mortality, nonfatal myocardial infarction, or ischemic stroke. The primary safety end point was hospital admissions for bleeding. We ascertained 12-month outcomes from the Quebec universal electronic health databases. We designed and analyzed the study within a Bayesian paradigm to supplement existing knowledge. The primary analysis was a Bayesian logistic regression model with an informed focused prior from previously randomly assigned North American patients. Robustness was evaluated with vague and other prespecified informative priors, spanning reasonable pre-existing beliefs. We defined clinically important benefits and harms as risk reductions exceeding a 10% difference.
We randomly assigned 1005 patients with acute coronary syndrome to ticagrelor ( = 450) or clopidogrel ( = 555). Major acute cardiovascular events occurred in 50 (11.1%) patients assigned to ticagrelor and 64 (11.5%) assigned to clopidogrel (relative risk [RR] 0.95, 95% credible interval 0.67-1.35, with a vague prior). The primary analysis with an informed focused prior resulted in probabilities of a clinically meaningful ticagrelor benefit (RR < 0.9), equivalence (0.9 ≤ RR ≤ 1.1) or harm (RR ≥ 1.1) of 2%, 41%, and 57%, respectively. For the safety end point, there was no consistent signal of benefit or harm with ticagrelor. Sensitivity analyses with a range of prior beliefs gave generally consistent results.
Whether we analyzed this trial with a vague or a range of reasonable informed priors, we found no strong evidence for the superiority of ticagrelor over clopidogrel in North American patients. Current guidelines favouring ticagrelor over clopidogrel might take this new evidence into future consideration.
Clinicaltrials.gov no. NCT04057300.
双联抗血小板治疗是急性冠状动脉综合征的标准治疗方法，但北美患者的最佳治疗方案仍存在不确定性。我们旨在比较阿司匹林（ASA）与替格瑞洛或氯吡格雷在加拿大蒙特利尔一家单一的三级学术中心的急性冠状动脉综合征患者中的有效性和安全性。
我们进行了一项实用、开放标签、时间聚类（2018年10月至2021年3月期间每两个月一次）的随机对照试验。主要有效性终点是全因死亡率、非致命性心肌梗死或缺血性中风的复合终点。主要安全性终点是因出血导致的住院治疗。我们从魁北克通用电子健康数据库中确定了12个月的结局。我们在贝叶斯范式内设计并分析了该研究，以补充现有知识。主要分析是一个贝叶斯逻辑回归模型，其先验来自先前随机分配的北美患者的有信息的聚焦先验。通过模糊和其他预先指定的信息先验评估稳健性，涵盖合理的先前信念。我们将临床上重要的益处和危害定义为风险降低超过10%的差异。
我们将1005例急性冠状动脉综合征患者随机分配至替格瑞洛组（n = 450）或氯吡格雷组（n = 555）。在分配至替格瑞洛组的患者中，50例（11.1%）发生了主要急性心血管事件，在分配至氯吡格雷组的患者中，64例（11.5%）发生了主要急性心血管事件（相对风险[RR] 0.95，95%可信区间0.67 - 1.35，先验模糊）。采用有信息的聚焦先验进行的主要分析得出，替格瑞洛具有临床意义上的益处（RR < 0.9）、等效性（0.9 ≤ RR ≤ 1.1）或危害（RR ≥ 1.1）的概率分别为2%、41%和57%。对于安全性终点，替格瑞洛没有一致的有益或有害信号。采用一系列先验信念进行的敏感性分析得出了大致一致的结果。
无论我们用模糊的还是一系列合理的有信息先验来分析该试验，我们都没有发现替格瑞洛在北美患者中优于氯吡格雷的有力证据。当前倾向于替格瑞洛优于氯吡格雷的指南可能会在未来考虑这一新证据。
Clinicaltrials.gov编号：NCT04057300。
