{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,6]],"date-time":"2026-11-06T21:27:30Z","timestamp":1794000450658,"version":"4.8.0"},"reference-count":35,"publisher":"American Medical Association (AMA)","issue":"12","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JAMA Cardiol"],"published-print":{"date-parts":[[2025,12,1]]},"abstract":"\n Importance<\/jats:title>\n Clonal hematopoiesis of indeterminate potential (CHIP) has been associated with increased risk of cardiovascular disease (CVD) events and mortality. However, there are no approved therapies for preventing or treating CHIP.<\/jats:p>\n <\/jats:sec>\n \n Objective<\/jats:title>\n To investigate whether low-dose aspirin might benefit older adults with CHIP for the primary prevention of CVD.<\/jats:p>\n <\/jats:sec>\n \n Design, Setting, and Participants<\/jats:title>\n 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. Enrollment was from March 2010 to December 2014, and the randomized trial ended in June 2017. 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. Of 19\u202f114 in the original trial, 11\u202f402 were included in the substudy, and 9434 were included in the analysis. Follow-up for this substudy went through June 2022, with data analysis in February 2025. 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.<\/jats:p>\n <\/jats:sec>\n \n Interventions<\/jats:title>\n Participants were randomized to aspirin, 100 mg, daily or placebo.<\/jats:p>\n <\/jats:sec>\n \n Main Outcomes and Measures<\/jats:title>\n CHIP was measured in blood specimens collected at trial entry. 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.<\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n 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) \u22652%, with 532 (5.6%) at \u226510% VAF. 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;\n P<\/jats:italic>\n \u2009=\u2009.09) or \u226510% VAF (aHR, 0.80, 95% CI, 0.57-1.12;\n P<\/jats:italic>\n \u2009=\u2009.19). However, CHIP was associated with increased risk of clinically significant bleeding (2%-10% VAF: aHR, 1.24; 95% CI 1.02-1.51;\n P<\/jats:italic>\n \u2009=\u2009.03; \u226510% VAF: aHR, 1.21; 95% CI, 0.85-1.73;\n P<\/jats:italic>\n \u2009=\u2009.28). 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; \u226510% VAF: HR, 1.33; 95% CI, 0.52-3.37; heterogeneity\n P<\/jats:italic>\n \u2009=\u2009.35) 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; \u226510% VAF: HR, 1.41; 95% CI, 0.49-4.07; heterogeneity\n P<\/jats:italic>\n \u2009=\u2009.91).\n <\/jats:p>\n <\/jats:sec>\n \n Conclusion and Relevance<\/jats:title>\n 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. However, participants with CHIP had a greater risk of clinically significant bleeding. 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.<\/jats:p>\n <\/jats:sec>\n \n Trial Registration<\/jats:title>\n \n ClinicalTrials.gov Identifier:\n NCT01038583<\/jats:ext-link>\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1001\/jamacardio.2025.3756","type":"journal-article","created":{"date-parts":[[2025,10,15]],"date-time":"2025-10-15T15:02:28Z","timestamp":1760540548000},"page":"1257","source":"Crossref","is-referenced-by-count":9,"title":["Clonal Hematopoiesis and Cardiovascular Disease and Bleeding Risk and the Effectiveness of Aspirin"],"prefix":"10.1001","volume":"10","author":[{"given":"Zoe K.","family":"McQuilten","sequence":"first","affiliation":[{"name":"School of Public Health and Preventive Medicine, Monash University, Melbourne, Victoria, Australia"},{"name":"Department of Haematology, Monash Health, Melbourne, Victoria, Australia"},{"name":"Department of Clinical Haematology, Alfred Health, Melbourne, Victoria, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Le T. 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