Importance Clinicians recommend enteric-coated aspirin to decrease gastrointestinal bleeding in secondary prevention of coronary artery disease even though studies suggest platelet inhibition is decreased with enteric-coated vs uncoated aspirin formulations. Objective To assess whether receipt of enteric-coated vs uncoated aspirin is associated with effectiveness or safety outcomes. Design, Setting, and Participants This is a post hoc secondary analysis of ADAPTABLE (Aspirin Dosing: A Patient-Centric Trial Assessing Benefits and Long-term Effectiveness), a pragmatic study of 15 076 patients with atherosclerotic cardiovascular disease having data in the National Patient-Centered Clinical Research Network. Patients were enrolled from April 19, 2016, through June 30, 2020, and randomly assigned to receive high (325 mg) vs low (81 mg) doses of daily aspirin. The present analysis assessed the effectiveness and safety of enteric-coated vs uncoated aspirin among those participants who reported aspirin formulation at baseline. Data were analyzed from November 11, 2019, to July 3, 2023. Intervention ADAPTABLE participants were regrouped according to aspirin formulation self-reported at baseline, with a median (IQR) follow-up of 26.2 (19.8-35.4) months. Main Outcomes and Measures The primary effectiveness end point was the cumulative incidence of the composite of myocardial infarction, stroke, or death from any cause, and the primary safety end point was major bleeding events (hospitalization for a bleeding event with use of a blood product or intracranial hemorrhage). Cumulative incidence at median follow-up for primary effectiveness and primary safety end points was compared between participants taking enteric-coated or uncoated aspirin using unadjusted and multivariable Cox proportional hazards models. All analyses were conducted for the intention-to-treat population. Results Baseline aspirin formulation used in ADAPTABLE was self-reported for 10 678 participants (median [IQR] age, 68.0 [61.3-73.7] years; 7285 men [68.2%]), of whom 7366 (69.0%) took enteric-coated aspirin and 3312 (31.0%) took uncoated aspirin. No significant difference in effectiveness (adjusted hazard ratio [AHR], 0.94; 95% CI, 0.80-1.09; P = .40) or safety (AHR, 0.82; 95% CI, 0.49-1.37; P = .46) outcomes between the enteric-coated aspirin and uncoated aspirin cohorts was found. Within enteric-coated aspirin and uncoated aspirin, aspirin dose had no association with effectiveness (enteric-coated aspirin AHR, 1.13; 95% CI, 0.88-1.45 and uncoated aspirin AHR, 0.99; 95% CI, 0.83-1.18; interaction P = .41) or safety (enteric-coated aspirin AHR, 2.37; 95% CI, 1.02-5.50 and uncoated aspirin AHR, 0.89; 95% CI, 0.49-1.64; interaction P = .07). Conclusions and Relevance In this post hoc secondary analysis of the ADAPTABLE randomized clinical trial, enteric-coated aspirin was not associated with significantly higher risk of myocardial infarction, stroke, or death or with lower bleeding risk compared with uncoated aspirin, regardless of dose, although a reduction in bleeding with enteric-coated aspirin cannot be excluded. More research is needed to confirm whether enteric-coated aspirin formulations or newer formulations will improve outcomes in this population. Trial Registration ClinicalTrials.gov Identifier: NCT02697916.

中文翻译：

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肠溶阿司匹林与未包衣阿司匹林在心血管疾病患者中的有效性和安全性：ADAPTABLE 随机临床试验的二次分析。

重要性 临床医生建议在冠心病二级预防中使用肠溶阿司匹林来减少胃肠道出血，尽管研究表明肠溶阿司匹林制剂与未包衣阿司匹林制剂相比会降低血小板抑制作用。目的 评估服用肠溶阿司匹林与未服用肠溶阿司匹林是否与有效性或安全性结果相关。设计、设置和参与者 这是对 ADAPTABLE（阿司匹林给药：一项以患者为中心的试验评估益处和长期有效性）的事后二次分析，这是一项针对 15 076 名动脉粥样硬化性心血管疾病患者的实用研究，数据来自国家患者-以临床研究网络为中心。患者于2016年4月19日至2020年6月30日期间入组，并随机分配接受高剂量（325毫克）和低剂量（81毫克）每日阿司匹林。本分析评估了基线时报告阿司匹林配方的参与者中肠溶阿司匹林与未包衣阿司匹林的有效性和安全性。数据分析时间为 2019 年 11 月 11 日至 2023 年 7 月 3 日。干预 ADAPTABLE 参与者根据基线时自我报告的阿司匹林配方进行重新分组，中位随访时间 (IQR) 为 26.2 (19.8-35.4) 个月。主要结局和措施 主要有效性终点是心肌梗死、卒中或全因死亡复合终点的累积发生率，主要安全性终点是主要出血事件（使用血液制品发生出血事件而住院）或颅内出血）。使用未经调整的多变量 Cox 比例风险模型，比较服用肠溶衣或未包衣阿司匹林的参与者在中位随访中主要有效性和主要安全性终点的累积发生率。所有分析都是针对意向治疗人群进行的。结果 ADAPTABLE 中使用的基线阿司匹林配方由 10 678 名参与者（中位 [IQR] 年龄，68.0 [61.3-73.7] 岁；7285 名男性 [68.2%]）自行报告，其中 7366 名 (69.0%) 服用肠溶阿司匹林3312 名（31.0%）服用了未包衣的阿司匹林。两组之间的有效性（调整后风险比 [AHR]，0.94；95% CI，0.80-1.09；P = .40）或安全性（AHR，0.82；95% CI，0.49-1.37；P = .46）结果没有显着差异。发现了肠溶阿司匹林和未包衣阿司匹林队列。在肠溶阿司匹林和非包衣阿司匹林中，阿司匹林剂量与有效性无关（肠溶阿司匹林 AHR，1.13；95% CI，0.88-1.45；非包衣阿司匹林 AHR，0.99；95% CI，0.83-1.18；交互作用 P = .41）或安全性（肠溶阿司匹林 AHR，2.37；95% CI，1.02-5.50，未包衣阿司匹林 AHR，0.89；95% CI，0.49-1.64；交互作用 P = 0.07）。结论和相关性 在 ADAPTABLE 随机临床试验的事后二次分析中，肠溶阿司匹林与心肌梗死、中风、与未包衣阿司匹林相比，无论剂量如何，死亡或出血风险较低，但不能排除肠溶阿司匹林可减少出血。需要更多的研究来确认肠溶阿司匹林制剂或新制剂是否会改善该人群的治疗结果。试验注册 ClinicalTrials.gov 标识符：NCT02697916。