Major Bleeding With Apixaban vs Aspirin: A Subanalysis of the ARTESiA Randomized Clinical Trial.

Background

To characterize major bleeding events (site and severity) and identify factors associated with major bleeding.

为了描述主要出血事件（部位和严重程度）并识别与主要出血相关的因素。

DESIGN, SETTING, AND PARTICIPANTS: This was a prespecified subanalysis of the ARTESiA population who received treatment.

这是ARTESiA人群的一个预先指定的亚组分析，他们接受了治疗。

This was an international, double-blind, double-dummy randomized clinical trial. Included were patients with 1 or more episodes of SCAF lasting 6 minutes to 24 hours with stroke risk factors (CHA2DS2-VASc score ≥3) or prior stroke without other risk factors.

这是一项国际性的、双盲的、双模拟的随机临床试验。纳入的患者有1次或多次SCAF发作，持续时间为6分钟至24小时，且具有中风风险因素（CHA2DS2-VASc评分≥3）或既往中风但无其他风险因素。

Study data were analyzed from August to November 2024.

研究数据从2024年8月至11月进行了分析。

Methods

Apixaban, 5 mg, twice daily (2.5 mg twice daily when indicated) or aspirin, 81 mg, once daily.

阿哌沙班，每日两次，每次5毫克（如有指示，每次2.5毫克）或阿司匹林，每日一次，每次81毫克。

main_outcomes_and_measures

Major bleeding adjudicated by a blinded committee according to International Society on Thrombosis and Hemostasis criteria.

主要出血事件由一个盲法委员会根据国际血栓与止血学会的标准进行裁定。

Results

A total of 3961 patients (mean [SD] age, 76.8 [7.6] years; 2535 male [64%]) were included in this analysis.

共有3961名患者（平均年龄[标准差]为76.8[7.6]岁；2535名为男性[占64%]）被纳入本分析中。

After a mean (SD) follow-up of 3.5 (1.8) years, 1 or more major bleeding episodes occurred in 133 patients, 86 of 1989 taking apixaban and 47 of 1972 taking aspirin (1.71 vs 0.94 per 100-patient-years; hazard ratio[HR], 1.80; 95% CI, 1.26-2.57).

在平均（标准差）随访3.5（1.8）年后，133名患者发生了1次或多次主要出血事件，其中1989名服用阿哌沙班的患者中有86例，1972名服用阿司匹林的患者中有47例（阿哌沙班组每100患者年为1.71例，阿司匹林组为0.94例；风险比[HR]，1.80；95%置信区间[CI]，1.26-2.57）。

The rates of intracranial (0.33 vs 0.40 per 100 patient-years; HR, 0.82; 95% CI, 0.43-1.57) and fatal (0.10% vs 0.16% per 100 patient-years; HR, 0.63; 95% CI, 0.20-1.91) bleeding were similar in the apixaban and aspirin groups, whereas the rate of gastrointestinal bleeding was higher in the apixaban group (0.89% vs 0.40% per 100 patient-years; HR, 2.23; 95% CI, 1.32-3.78).

阿哌沙班组和阿司匹林组的颅内出血率（分别为每100患者年0.33例和0.40例；HR，0.82；95%置信区间[CI]，0.43-1.57）和致命性出血率（分别为每100患者年0.10%和0.16%；HR，0.63；95%置信区间[CI]，0.20-1.91）相似，而阿哌沙班组的胃肠道出血率更高（分别为每100患者年0.89%和0.40%；HR，2.23；95%置信区间[CI]，1.32-3.78）。

Among 133 index major bleeding events, those that occurred with apixaban were less likely to occur at critical sites (27.9% [24 of 86] vs 46.8% [22 of 47]; P = .03) including intracranial (18.6% [16 of 86] vs 42.6% [20 of 47]; P = .003).

在133起主要出血事件中，使用阿哌沙班的事件在关键部位发生的可能性较低（27.9% [24/86] 对比 46.8% [22/47]; P = .03），包括颅内出血（18.6% [16/86] 对比 42.6% [20/47]; P = .003）。

Most major bleeding events were nonemergencies characterized by decreased hemoglobin greater than or equal to 2 g/dL.

大多数主要出血事件是非紧急的，其特征是血红蛋白减少大于或等于2 g/dL。

Factors associated with major bleeding included nonsteroidal anti-inflammatory drug (NSAID) use (HR, 10.25; 95% CI, 6.57-15.99), cancer (HR, 2.87; 95% CI, 1.49-5.53), randomization to apixaban (HR, 1.84; 95% CI, 1.29-2.63), and age (HR, 1.47; 95% CI, 1.28-1.67, per 5-year increase).

与主要出血相关的因素包括非甾体抗炎药（NSAID）使用（HR，10.25；95% CI，6.57-15.99），癌症（HR，2.87；95% CI，1.49-5.53），随机分配到阿哌沙班（HR，1.84；95% CI，1.29-2.63），以及年龄（HR，1.47；95% CI，1.28-1.67，每增加5岁）。

conclusions_and_relevance

Results of this subanalysis of the ARTESiA randomized clinical trial found that although the rate of major gastrointestinal bleeding was higher in patients with SCAF who were treated with apixaban vs aspirin, rates of fatal and intracranial bleeding were not different.

ARTESiA随机临床试验的这一亚组分析结果显示，尽管在治疗SCAF患者时，使用阿哌沙班相比阿司匹林的主要胃肠道出血率更高，但致命性和颅内出血率没有差异。

Most major bleeding events were nonemergencies characterized by a decrease in hemoglobin level greater than or equal to 2 g/dL.

大多数主要出血事件为非紧急情况，其特征为血红蛋白水平下降大于或等于2 g/dL。

NSAID use, cancer, randomization to apixaban, and increasing age were associated with an increased risk of major bleeding.

使用非甾体抗炎药、癌症、随机分配至阿哌沙班以及年龄增长与主要出血风险增加相关。

trial_registration

ClinicalTrials.gov Identifier: NCT01938248.

临床试验注册号：NCT01938248。