BACKGROUND Acetylsalicylic acid (ASA) is a frequently used antiplatelet agent, although some individuals have reduced antiplatelet responses on ASA, with recurrent ischemic events. It has been proposed that shortening the ASA dosing interval may overcome the time-dependent renewal of the drug target, leading to a greater antiplatelet effect. We conducted a systematic review of randomized controlled trials (RCTs) to determine the efficacy of once- versus twice-daily ASA in conditions with increased platelet turnover. METHODS We conducted a systematic review and meta-analysis by searching the CENTRAL, MEDLINE, and Embase databases for RCTs assessing once- versus twice-daily ASA. Data were screened, extracted, and appraised by two independent reviewers, and were pooled using a random-effects model. The primary outcomes were major adverse cardiovascular events (MACEs) and serum thromboxane B2 (TxB2). Other pharmacodynamic measures were retrieved as secondary outcomes. Results were reported as mean differences with corresponding 95% confidence intervals (CIs). We followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. RESULTS Seven RCTs were included, enrolling 379 participants overall. None of the studies reported clinical outcomes. Pooled results showed that compared with once-daily ASA, twice-daily ASA was associated with a decrease in mean TxB2 of 1.42 ng/mL (95% CI - 2.71 to - 0.13; I2 = 66%). We found no differences in subgroup analyses based on disease subtype, trial blinding, or trial design. A greater antiplatelet activity of the twice-daily regimen was also found when using PFA-100-ADP methods, although not when using the VerifyNow, LTA-AA, and multiplate methods. CONCLUSIONS Twice-daily ASA was associated with a greater antiplatelet effect compared with standard once-daily ASA.

中文翻译：

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血栓事件高风险患者服用阿司匹林与每日服用两次：系统评价和荟萃分析。

背景乙酰水杨酸 (ASA) 是一种常用的抗血小板药物，尽管一些个体对 ASA 的抗血小板反应降低，并伴有复发性缺血事件。有人提出缩短 ASA 给药间隔可能会克服药物靶标的时间依赖性更新，从而产生更大的抗血小板作用。我们对随机对照试验 (RCT) 进行了系统评价，以确定每日一次与每日两次 ASA 在血小板周转增加的情况下的疗效。方法 我们通过在 CENTRAL、MEDLINE 和 Embase 数据库中搜索评估每天一次和两次 ASA 的 RCT 进行了系统评价和荟萃分析。数据由两名独立审查员筛选、提取和评估，并使用随机效应模型汇总。主要结局是主要不良心血管事件 (MACE) 和血清血栓素 B2 (TxB2)。其他药效学指标被检索为次要结果。结果报告为具有相应 95% 置信区间 (CI) 的平均差异。我们遵循了系统评价和元分析的首选报告项目 (PRISMA) 指南。结果 纳入了 7 个 RCT，总共招募了 379 名参与者。没有一项研究报告了临床结果。汇总结果显示，与每日一次 ASA 相比，每日两次 ASA 与平均 TxB2 降低 1.42 ng/mL 相关（95% CI - 2.71 至 - 0.13；I2 = 66%）。我们发现基于疾病亚型、试验盲法或试验设计的亚组分析没有差异。使用 PFA-100-ADP 方法时也发现每日两次方案的抗血小板活性更高，但使用 VerifyNow、LTA-AA 和多板方法时则不然。结论与标准的每天一次的 ASA 相比，每天两次的 ASA 与更大的抗血小板作用相关。