BACKGROUND Antiplatelet therapy is recommended among patients with established atherosclerosis. We compared monotherapy with a P2Y12 inhibitor versus aspirin for secondary prevention. METHODS In this systematic review and meta-analysis, all randomised trials comparing P2Y12 inhibitor with aspirin monotherapy for secondary prevention in patients with cerebrovascular, coronary, or peripheral artery disease were evaluated for inclusion. On Dec 18, 2019, we searched PubMed, Embase, BioMedCentral, Google Scholar, and the Cochrane Central Register of Controlled Trials. Additionally, we reviewed references from identified articles and searched abstracts from 2017 to 2019 presented at relevant scientific meetings. Data about year of publication, inclusion and exclusion criteria, sample size, baseline patients' features including the baseline condition determining study inclusion (ie, cerebrovascular, coronary, or peripheral artery disease), P2Y12 inhibitor type and dosage, aspirin dosage, endpoint definitions, effect estimates, follow-up duration, and percentage of patients lost to follow-up were collected. Odds ratios (ORs) and 95% CIs were used as metric of choice for treatment effects with random-effects models. Co-primary endpoints were myocardial infarction and stroke. Key secondary endpoints were all-cause death and vascular death. Heterogeneity was assessed with the I2 index. This study is registered with PROSPERO (CRD42018115037). FINDINGS A total of nine randomised trials were identified and included in this study, and 42 108 patients randomly allocated to a P2Y12 inhibitor (n=21 043) or aspirin (n=21 065) were included in our analyses. Patients who received a P2Y12 inhibitor had a borderline reduction for the risk of myocardial infarction compared with those who received aspirin (OR 0·81 [95% CI 0·66-0·99]; I2=10·9%). Risks of stroke (OR 0·93 [0·82-1·06]; I2=34·5%), all-cause death (OR 0·98 [0·89-1·08]; I2=0%), and vascular death (OR 0·97 [0·86-1·09]; I2=0%) did not differ between patients who received a P2Y12 inhibitor and those who received aspirin. Similarly, the risk of major bleeding (OR 0·90 [0·74-1·10]; I2=3·9%) did not differ between patients who received a P2Y12 inhibitor and those who received aspirin. The number needed to treat to prevent one myocardial infarction with P2Y12 inhibitor monotherapy was 244 patients. Findings were consistent regardless of the type of P2Y12 inhibitor used. INTERPRETATION Compared with aspirin monotherapy, P2Y12 inhibitor monotherapy is associated with a risk reduction for myocardial infarction and a comparable risk of stroke in the setting of secondary prevention. The benefit of P2Y12 inhibitor monotherapy is of debatable clinical relevance, in view of the high number needed to treat to prevent a myocardial infarction and the absence of any effect on all-cause and vascular mortality. FUNDING Italian Ministry of Education.

中文翻译：

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P2Y12抑制剂或阿司匹林的单一疗法对已确立的动脉粥样硬化患者的二级预防：系统评价和荟萃分析。

背景技术在已确定的动脉粥样硬化的患者中推荐抗血小板治疗。我们比较了单一疗法与P2Y12抑制剂与阿司匹林在二级预防中的作用。方法在这项系统的回顾和荟萃分析中，评估了所有比较P2Y12抑制剂和阿司匹林单一疗法对脑血管，冠状动脉或周围动脉疾病患者进行二级预防的随机试验。在2019年12月18日，我们搜索了PubMed，Embase，BioMedCentral，Google Scholar和Cochrane对照试验中央注册系统。此外，我们审查了在相关科学会议上发表的2017年至2019年发表的文章和参考摘要。有关发表年份，纳入和排除标准，样本量，基线患者的数据 特征包括确定研究纳入的基线条件（即脑血管，冠状动脉或外周动脉疾病），P2Y12抑制剂类型和剂量，阿司匹林剂量，终点定义，作用估计，随访时间以及失去随访的患者百分比被收集。奇数比（OR）和95％CI被用作随机效应模型治疗效果的选择指标。共同的主要终点是心肌梗塞和中风。主要的次要终点是全因死亡和血管死亡。异质性用I2指数评估。该研究已在PROSPERO注册（CRD42018115037）。结果总共鉴定出9项随机试验并纳入本研究，我们的分析包括42108例随机分配给P2Y12抑制剂（n = 21 043）或阿司匹林（n = 21 065）的患者。与接受阿司匹林治疗的患者相比，接受P2Y12抑制剂治疗的患者发生心肌梗塞的危险性降低（OR 0·81 [95％CI 0·66-0·99]； I2 = 10·9％）。中风的风险（OR 0·93 [0·82-1·06]； I2 = 34·5％），全因死亡（OR 0·98 [0·89-1·08]； I2 = 0％） ，和接受P2Y12抑制剂的患者与接受阿司匹林的患者的血管死亡（OR 0·97 [0·86-1·09]； I2 = 0％）无差异。同样，接受P2Y12抑制剂的患者和接受阿司匹林的患者之间的大出血风险（OR 0·90 [0·74-1·10]； I2 = 3·9％）也没有差异。用P2Y12抑制剂单一疗法治疗可预防1例心肌梗塞的人数为244例。无论使用何种P2Y12抑制剂，结果都是一致的。解释与阿司匹林单一疗法相比，在二级预防中，P2Y12抑制剂单一疗法可降低心肌梗塞的风险，并具有相当的中风风险。鉴于需要大量治疗来预防心肌梗塞，并且对全因和血管死亡率没有任何影响，P2Y12抑制剂单一疗法的益处在临床上仍有争议。资金意大利教育部。