State Key Laboratory of Cardiovascular Disease.
Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
Medicine (Baltimore). 2021 Feb 12;100(6):e24366. doi: 10.1097/MD.0000000000024366.
Pharmacokinetic and pharmacodynamic study showed a lower clopidogrel response when coprescribed with proton pump inhibitors (PPIs). Despite this, PPIs is necessary for patients treated with long term dual antiplatelet therapy (DAPT). Ethnic variance also played a different effect on clopidogrel response. Our study evaluated the effect of concomitant use of DAPT and PPIs and assessed whether ethnic variance exert different effect on clinical outcomes.
We carefully searched EMBASE, PubMed/Medline databases, and the Cochrane library in April 2019. The primary endpoint was major adverse cardiovascular and cerebrovascular events (MACCE) and individual endpoints reported. We also focused on bleeding events. Studies were excluded if the follow-up were <12 months and patients were not treated with clopidogrel after stent implantation.
A total of 18 studies were included in the systematic review (involving 79,670 patients). No randomized controlled trials (RCTs) were included. PPIs comedication were associated with increased MACCE (odds ratio [OR] = 1.38; 95% confidence interval [CI] = 1.28-1.49) while not associated with decreased bleeding risks, such as gastrointestinal bleeding (OR = 1.05; 95% CI = 0.53-2.11). PPIs comedication were associated with increased risk for all endpoints among Caucasian population while not with increased risk for MACE (OR = 1.20; 95% CI = 0.99-1.39), all-cause death (OR = 1.24; 95% CI = 0.74-2.06), cardiac-death (OR = 1.29; 95% CI = 0.64-2.57) among Asian population.
PPIs comedication were associated with adverse clinical outcomes, and ethnic variance may exert different effect on clinical outcomes. Subgroup analysis indicated that concomitant use of PPI might be suitable for Asian patients after stent implantation.
药代动力学和药效学研究表明,质子泵抑制剂(PPIs)与氯吡格雷联合使用时,氯吡格雷的反应较低。尽管如此,长期双联抗血小板治疗(DAPT)的患者仍需要使用 PPI。种族差异也对氯吡格雷的反应产生不同的影响。我们的研究评估了 DAPT 和 PPI 同时使用的效果,并评估了种族差异是否对临床结果产生不同的影响。
我们于 2019 年 4 月仔细检索了 EMBASE、PubMed/Medline 数据库和 Cochrane 图书馆。主要终点是主要不良心血管和脑血管事件(MACCE)和报告的个别终点。我们还关注出血事件。如果随访时间<12 个月且患者在支架植入后未接受氯吡格雷治疗,则排除研究。
系统评价共纳入 18 项研究(涉及 79670 名患者)。未纳入随机对照试验(RCT)。PPIs 联合用药与 MACCE 增加相关(比值比[OR]=1.38;95%置信区间[CI]=1.28-1.49),而与胃肠道出血等出血风险降低无关(OR=1.05;95%CI=0.53-2.11)。PPIs 联合用药与高加索人群所有终点的风险增加相关,但与 MACE(OR=1.20;95%CI=0.99-1.39)、全因死亡(OR=1.24;95%CI=0.74-2.06)、心脏死亡(OR=1.29;95%CI=0.64-2.57)的风险增加无关。
PPIs 联合用药与不良临床结局相关,种族差异可能对临床结局产生不同的影响。亚组分析表明,支架植入后,PPI 联合用药可能适用于亚洲患者。