Low-Dose Aspirin and the Risk of Stroke and Intracerebral Bleeding in Healthy Older People: Secondary Analysis of a Randomized Clinical Trial
Geoffrey C. Cloud, Jeff D. Williamson, Le Thi Phuong Thao, Cammie Tran, Charles B. Eaton, Rory Wolfe, Mark R. Nelson, Christopher M. Reid, Anne B. Newman, Jessica Lockery, Sharyn M. Fitzgerald, Anne M. Murray, Raj C. Shah, Robyn L. Woods, Geoffrey A. Donnan, John J. McNeil
JAMA Network Open：2023/07/26
Importance
Low-dose aspirin has been widely used for primary and secondary prevention of stroke. The balance between potential reduction of ischemic stroke events and increased intracranial bleeding has not been established in older individuals.
ObjectiveTo establish the risks of ischemic stroke and intracranial bleeding among healthy older people receiving daily low-dose aspirin.
Design, Setting, and ParticipantsThis secondary analysis of the Aspirin in Reducing Events in the Elderly (ASPREE) randomized, double-blind, placebo-controlled trial of daily low-dose aspirin was conducted among community-dwelling people living in Australia or the US. Participants were older adults free of symptomatic cardiovascular disease. Recruitment took place between 2010 and 2014, and participants were followed up for a median (IQR) of 4.7 (3.6-5.7) years. This analysis was completed from August 2021 to March 2023.
InterventionsDaily 100-mg enteric-coated aspirin or matching placebo.
Main Outcomes and MeasuresStroke and stroke etiology were predetermined secondary outcomes and are presented with a focus on prevention of initial stroke or intracranial bleeding event. Outcomes were assessed by review of medical records.
ResultsAmong 19 114 older adults (10 782 females [56.4%]; median [IQR] age, 74 [71.6-77.7] years), 9525 individuals received aspirin and 9589 individuals received placebo. Aspirin did not produce a statistically significant reduction in the incidence of ischemic stroke (hazard ratio [HR], 0.89; 95% CI, 0.71-1.11). However, a statistically significant increase in intracranial bleeding was observed among individuals assigned to aspirin (108 individuals [1.1%]) compared with those receiving placebo (79 individuals [0.8%]; HR, 1.38; 95% CI, 1.03-1.84). This occurred by an increase in a combination of subdural, extradural, and subarachnoid bleeding with aspirin compared with placebo (59 individuals [0.6%] vs 41 individuals [0.4%]; HR, 1.45; 95% CI, 0.98-2.16). Hemorrhagic stroke was recorded in 49 individuals (0.5%) assigned to aspirin compared with 37 individuals (0.4%) in the placebo group (HR, 1.33; 95% CI, 0.87-2.04).
Conclusions and RelevanceThis study found a significant increase in intracranial bleeding with daily low-dose aspirin but no significant reduction of ischemic stroke. These findings may have particular relevance to older individuals prone to developing intracranial bleeding after head trauma.
Trial RegistrationISRCTN.org Identifier:ISRCTN83772183
重要性低剂量阿司匹林已被广泛用于中风的一级和二级预防。在老年人中，缺血性卒中事件的潜在减少和颅内出血增加之间的平衡尚未建立。目的确定每天接受低剂量阿司匹林治疗的健康老年人发生缺血性卒中和颅内出血的风险，和参与者这项阿司匹林减少老年人事件（ASPREE）的随机、双盲、安慰剂对照试验在澳大利亚或美国的社区居民中进行。参与者是没有症状性心血管疾病的老年人。招募在2010年至2014年间进行，参与者的中位随访时间为4.7年（3.6-5.7年）。该分析于2021年8月至2023年3月完成。干预措施每日100 mg肠溶阿司匹林或匹配的安慰剂。主要结果和测量中风和中风病因是预先确定的次要结果，重点是预防最初的中风或颅内出血事件。结果在19例患者中 114名老年人（10 782名女性[56.4%]；中位[IQR]年龄，74[71.6-77.7]岁），9525人接受阿司匹林治疗，9589人接受安慰剂治疗。阿司匹林并没有显著降低缺血性卒中的发生率（危险比[HR]，0.89；95%CI，0.71-1.11），与安慰剂组（79人[0.8%]；HR，1.38；95%CI，1.03-1.84）相比，服用阿司匹林组（108人[1.1%]）的颅内出血有统计学意义的增加，与安慰剂组相比，服用阿司匹林的蛛网膜下腔出血（59人[0.6%]vs 41人[0.4%]；HR，1.45；95%CI，0.98-2.16）。与安慰剂组的37人（0.4%）相比，服用阿斯匹林的49人（0.5%）记录了出血性卒中（HR，1.33；95%CI，0.87-2.04）每日低剂量阿司匹林，但缺血性卒中没有显著减少。这些发现可能与头部创伤后容易发生颅内出血的老年人特别相关。试验注册ISRCTN.org标识符：ISRCTN83772183
医生有时会建议老年人每天服用低剂量（75~100毫克）的阿司匹林，以便稀释血液来降低缺血性中风（最常见的一类中风）的风险。但最近一项发表在《JAMA网络开放获取》（JAMA Network Open）上的研究表明，阿司匹林在稀释血液方面并不比安慰剂更有效，反而会增加脑出血的风险。
