Clonal Hematopoiesis and Cardiovascular Disease and Bleeding Risk and the Effectiveness of Aspirin.

However, there are no approved therapies for preventing or treating CHIP.

然而，目前尚无批准用于预防或治疗CHIP的疗法。

Background

To investigate whether low-dose aspirin might benefit older adults with CHIP for the primary prevention of CVD.

研究低剂量阿司匹林是否可能对有CHIP的老年人在CVD的一级预防中带来益处。

DESIGN, SETTING, AND PARTICIPANTS: This was a prespecified substudy of the Aspirin in Reducing Events in the Elderly (ASPREE) double-blind, randomized clinical trial of daily low-dose aspirin vs placebo evaluating disability-free survival, which took place at primary and community care facilities in the US and Australia.

设计、环境和参与者：这是Aspirin in Reducing Events in the Elderly (ASPREE)每日低剂量阿司匹林与安慰剂对照的双盲随机临床试验的预定子研究，评估无残疾生存，该试验在美国和澳大利亚的初级和社区护理机构进行。

Enrollment was from March 2010 to December 2014, and the randomized trial ended in June 2017.

招募工作从2010年3月开始至2014年12月结束，随机试验在2017年6月结束。

Community-dwelling Australian adults aged 70 years and older without a diagnosed cardiovascular event, atrial fibrillation, a serious intercurrent illness likely to cause death within the next 5 years, anemia, or a current or recurrent condition with a high risk of bleeding were included in the original study.

原始研究纳入了居住在社区的70岁及以上的澳大利亚成年人，他们没有被诊断出心血管事件、房颤、可能在接下来5年内导致死亡的严重并发疾病、贫血，或者当前或反复出现的高出血风险状况。

Of 19 114 in the original trial, 11 402 were included in the substudy, and 9434 were included in the analysis.

在原始试验的19,114名患者中，有11,402名被纳入子研究，其中9,434名被纳入分析。

Follow-up for this substudy went through June 2022, with data analysis in February 2025.

这项子研究的随访截止至2022年6月，数据分析完成于2025年2月。

In-trial median (IQR) follow-up time was 4.6 (3.5-5.6) years, and posttrial observational follow-up was 8.7 (7.5-10.1) years from randomization.

试验期间的中位随访时间（四分位数间距）为4.6（3.5-5.6）年，随机化后的随访观察时间为8.7（7.5-10.1）年。

Methods

Participants were randomized to aspirin, 100 mg, daily or placebo.

参与者被随机分配到每日100毫克阿司匹林或安慰剂组。

main_outcomes_and_measures

CHIP was measured in blood specimens collected at trial entry.

在试验开始时收集的血液样本中测量了CHIP。

Major adverse cardiovascular events (MACEs), including fatal and nonfatal ischemic stroke, nonfatal myocardial infarction and coronary heart disease death, and clinically significant bleeding were adjudicated by independent expert committees blinded to trial-group assignments.

主要不良心血管事件（MACEs），包括致命和非致命性缺血性中风、非致命性心肌梗死和冠心病死亡，以及临床显著的出血事件，由独立的专家委员会进行裁定，该委员会对试验组分配情况不知情。

Results

A total of 9434 participants (median [IQR] age, 73.7 [71.6-77.1] years; 5067 [54%] female) provided a sample at baseline for analysis, 2124 of whom (23%) had CHIP at variant allele fraction (VAF) ≥2%, with 532 (5.6%) at ≥10% VAF.

共有9434名参与者（中位年龄[四分位数间距]为73.7[71.6-77.1]岁；5067名[54%]为女性）在基线时提供了样本以供分析，其中2124名（23%）在变异等位基因频率（VAF）≥2%时有CHIP，532名（5.6%）在VAF≥10%时有CHIP。

CHIP was not associated with increased risk of MACEs at 2% to 10% VAF (adjusted hazard ratio[aHR], 0.84, 95% CI, 0.68-1.03; P = .09) or ≥10% VAF (aHR, 0.80, 95% CI, 0.57-1.12; P = .19).

在VAF为2%至10%时，CHIP与主要不良心血管事件（MACEs）风险增加无关（调整后风险比[aHR]，0.84，95%置信区间[CI]，0.68-1.03；P = .09），在VAF≥10%时也是如此（aHR，0.80，95% CI，0.57-1.12；P = .19）。

However, CHIP was associated with increased risk of clinically significant bleeding (2%-10% VAF: aHR, 1.24; 95% CI 1.02-1.51; P = .03; ≥10% VAF: aHR, 1.21; 95% CI, 0.85-1.73; P = .28).

然而， CHIP 与临床显著出血风险增加相关（2%-10% VAF：调整后风险比aHR，1.24；95% 置信区间CI 1.02-1.51；P = .03；≥10% VAF：aHR，1.21；95% CI，0.85-1.73；P = .28）。

There was no evidence of a differential effect of aspirin according to presence of CHIP on MACEs (without CHIP: HR, 0.91; 95% CI, 0.72-1.16; 2%-10% VAF: HR, 1.40; 95% CI, 0.77-2.53; ≥10% VAF: HR, 1.33; 95% CI, 0.52-3.37; heterogeneity P = .35) or clinically significant bleeding (without CHIP: HR, 1.64; 95% CI, 1.22-2.30; 2%-10% VAF: HR, 1.45; 95% CI, 0.82-2.57; ≥10% VAF: HR, 1.41; 95% CI, 0.49-4.07; heterogeneity P = .91).

没有证据表明阿司匹林根据 CHIP 的存在对主要不良心血管事件（MACEs）有差异性影响（无 CHIP：风险比 HR，0.91；95% 置信区间 CI，0.72-1.16；2%-10% VAF：HR，1.40；95% CI，0.77-2.53；≥10% VAF：HR，1.33；95% CI，0.52-3.37；异质性 P = .35）或临床显著出血（无 CHIP：HR，1.64；95% CI，1.22-2.30；2%-10% VAF：HR，1.45；95% CI，0.82-2.57；≥10% VAF：HR，1.41；95% CI，0.49-4.07；异质性 P = .91）。

conclusion_and_relevance

In this secondary analysis of a randomized clinical trial of daily low-dose aspirin in healthy adults 70 years and older, CHIP was not associated with higher CVD risk.

在这项针对70岁及以上健康成年人每日低剂量阿司匹林的随机临床试验的次要分析中，细胞遗传学造血异常（CHIP）与更高的心血管疾病（CVD）风险无关。

However, participants with CHIP had a greater risk of clinically significant bleeding.

然而，携带细胞遗传学造血异常（CHIP）的参与者有更高的临床显著性出血风险。

There was no evidence that participants with CHIP were more likely than those without CHIP to benefit or experience more harm from aspirin when used for primary prevention of CVD events.

没有证据表明，与没有CHIP的参与者相比，有CHIP的参与者在使用阿司匹林进行心血管事件的一级预防时，更有可能受益或经历更多的伤害。

trial_registration

ClinicalTrials.gov Identifier: NCT01038583.

ClinicalTrials.gov注册号：NCT01038583。