Hammami Imen, Mafham Marion, Emberson Jonathan, Offer Alison, Hopewell Jemma C, Armitage Jane, Baigent Colin, Parish Sarah
Clinical Trial Service Unit and Epidemiological Studies Unit, University of Oxford Nuffield Department of Population Health, Oxford, UK.
Clinical Trial Service Unit and Epidemiological Studies Unit, University of Oxford Nuffield Department of Population Health, Oxford, UK
Heart. 2025 Jul 14;111(15):716-721. doi: 10.1136/heartjnl-2024-324841.
In the primary prevention setting, low-dose aspirin reduces major vascular events (MVEs) by approximately 11% but increases major bleeding (MB) by 40-50%, implying that net benefit will be most evident when the MVE-to-MB ratio is >4. This study aimed to derive cross-validated risk scores for MB and MVE and use the MVE-to-MB ratio to identify groups who may derive differing net benefits from treatment.
431 167 UK Biobank participants without known atherosclerotic cardiovascular disease at baseline were followed through record linkage for incident MVEs (myocardial infarction, non-haemorrhagic stroke, transient ischaemic attack, arterial revascularisation or vascular death) and MB (gastrointestinal and intracranial bleeds with hospital admission for ≥2 days). Risk scores were derived for MVE and MB using Cox proportional hazards models with cross-validation. Ratios of observed MVE-to-MB rates were calculated across risk categories.
During a median follow-up of 12 years, 18 310 participants suffered an MVE and 5352 an MB. MB risk was highest among participants with frailty, prior bleeds, cancer, liver disease or renal dysfunction, with a 4.3-fold difference in risk between the highest and lowest fifths of MB risk (HR 4.3, 95% CI 3.87 to 4.77). The MVE-to-MB ratio was ≤2.6 in the highest MB risk groups and ≥4 in lower MB risk categories.
The derived models using routinely available disease history and laboratory measurements improved distinction of the MVE-to-MB ratio compared with using conventional models for MB risk including vascular risk factors. Such models can help identify those with moderate MVE risk but low MB risk who may benefit from low-dose aspirin.
在一级预防中，低剂量阿司匹林可使主要血管事件（MVE）减少约11%，但使大出血（MB）增加40 - 50%，这意味着当MVE与MB的比率大于4时，净获益最为明显。本研究旨在得出经交叉验证的MB和MVE风险评分，并使用MVE与MB的比率来识别可能从治疗中获得不同净获益的人群。
对431167名英国生物银行的参与者进行随访，这些参与者在基线时无已知的动脉粥样硬化性心血管疾病，通过记录链接来追踪发生的MVE（心肌梗死、非出血性卒中、短暂性脑缺血发作、动脉血运重建或血管性死亡）和MB（胃肠道和颅内出血且住院≥2天）。使用Cox比例风险模型并经交叉验证得出MVE和MB的风险评分。计算各风险类别中观察到的MVE与MB发生率的比率。
在中位随访12年期间，18310名参与者发生了MVE，5352名参与者发生了MB。MB风险在虚弱、既往有出血史、癌症、肝病或肾功能不全的参与者中最高，MB风险最高五分位数与最低五分位数之间的风险相差4.3倍（风险比4.3，95%置信区间3.87至4.77）。在MB风险最高的组中，MVE与MB的比率≤2.6，而在MB风险较低的类别中≥4。
与使用包括血管危险因素在内的MB风险传统模型相比，利用常规可得的疾病史和实验室测量得出的模型改善了MVE与MB比率的区分度。此类模型有助于识别那些MVE风险中等但MB风险较低且可能从低剂量阿司匹林中获益的人群。
