近日，意大利那不勒斯大学教授Raffaele Piccolo团队研究了冠状动脉疾病患者抗血栓治疗疗效和安全性的性别差异。该研究于2025年7月29日发表在《英国医学杂志》上。

为了评价已确诊冠心病患者抗血栓治疗效果的性别差异，研究组检索Ovid Medline和Embase数据库从成立到2025年4月中报告性别分层结局的随机对照试验，包括缺血和大出血事件，并比较任何实验性与对照抗血栓治疗冠状动脉疾病的策略，对这些文献进行系统回顾和荟萃分析。由2位审稿人提取数据并评估偏倚风险。为了避免生态偏差，研究组建立了一个试验框架来评估抗血栓治疗效果中与性别相关的异质性。特定性别的风险估计报告为95%置信区间的风险比，而试验水平的风险比合并为反方差模型。

研究组共纳入了33项试验，涉及274,433名受试者，其中72,601名（中位比例为25%）为女性。患者入组时间为1999年至2025年。在22项试验中，共有187,580名患者发生6018例死亡（使用强化抗栓治疗的患者中有3064例死亡，使用非强化治疗的患者中有2954例死亡）。强化与非强化抗栓治疗在女性和男性中的全因死亡相对风险相当，无性别交互作用（交互风险比1.06，95%置信区间0.94至1.19；交互P值=0.33；I²=0.00%；异质性P值=0.76）。

在172,504名患者中，共发生7558例心肌梗死。强化抗栓治疗在男性和女性中均使心肌梗死风险降低约15%（交互风险比1.05，0.95至1.17；交互P值=0.36；I²=14.05%；异质性P值=0.28）。相反，无论性别如何，强化与非强化抗栓治疗相比，重大出血事件显著增加约40%（交互风险比0.99，0.86至1.15；交互P值=0.93；I²=33.56%；异质性P值=0.05）。总体而言，共发生4003例主要出血事件（使用强化治疗的患者中有2384例，使用非强化治疗的患者中有1619例）。

研究结果表明，在确诊的冠状动脉疾病患者中，抗血栓治疗在女性和男性中提供一致的疗效和安全性结果。

附：英文原文

Title: Sex related differences in efficacy and safety of antithrombotic therapy in patients with coronary artery disease: systematic review and meta-analysis

Author: Raffaele Piccolo, Angelo Laino, Antonio Pio Vitale, Anna Franzone, Giovanni Esposito

Issue&Volume: 2025/07/29

Abstract:

Objective To evaluate sex related differences in the treatment effect of antithrombotic therapy in patients with established coronary artery disease.

Design Systematic review and meta-analysis.

Data sources Ovid Medline and Embase databases from inception to April 2025.

Inclusion criteria Included studies were randomised controlled trials reporting sex stratified outcomes, including ischaemic and major bleeding events, and comparing any experimental versus control antithrombotic strategy in coronary artery disease.

Data extraction and synthesis Two reviewers extracted data and assessed the risk of bias. To avoid ecological bias, a within trial framework was developed to evaluate sex related heterogeneity in the treatment effect of antithrombotic therapies. Sex specific risk estimates were reported as hazard ratios with 95% confidence intervals, whereas trial level ratios of hazard ratios were pooled with an inverse variance model.

Results A total of 33 trials enrolling 274433 participants, of which 72601 (median proportion 25%) were women, were included. Patients were enrolled between 1999 and 2025. A total of 6018 deaths occurred in 187580 patients across 22 trials (3064 deaths in patients using more intensive antithrombotic therapies and 2954 in those using less intensive therapies). The relative risk of all cause death was comparable for more intensive versus less intensive antithrombotic therapies in both women and men, without sex based interaction (interaction hazard ratio 1.06, 95% confidence interval 0.94 to 1.19; P for interaction=0.33; I2=0.00%; P for heterogeneity=0.76). 7558 myocardial infarctions occurred among 172504 patients. More intensive antithrombotic therapies were associated with a reduced risk of myocardial infarction by ~15% in both men and women (interaction hazard ratio 1.05, 0.95 to 1.17; P for interaction=0.36; I2=14.05%; P for heterogeneity=0.28). Conversely, major bleeding was significantly increased by ~40% for more intensive versus less intensive antithrombotic therapies irrespective of sex (interaction hazard ratio 0.99, 0.86 to 1.15; P for interaction=0.93; I2=33.56%; P for heterogeneity=0.05). Overall, 4003 major bleeding events occurred (2384 in patients using more intensive therapies and 1619 in those using less intensive therapies).

Conclusions Antithrombotic therapies in patients with established coronary artery disease provided consistent efficacy and safety outcomes in women and men.

DOI: 10.1136/bmj-2024-082974

Source: https://www.bmj.com/content/390/bmj-2024-082974