Gulilat Markus, Jandoc Racquel, Jeyakumar Nivethika, McArthur Eric, Garg Amit X, Kim Richard B, Tirona Rommel G, Schwarz Ute I
Division of Clinical Pharmacology, Department of Medicine, Western University, London, Ontario, Canada.
Department of Physiology and Pharmacology, Western University, London, Ontario, Canada.
CJC Open. 2021 Sep 10;4(1):56-64. doi: 10.1016/j.cjco.2021.09.002. eCollection 2022 Jan.
Evidence from clinical trials suggests a differential effect of sex on the effectiveness and safety of direct oral anticoagulants (DOACs) for stroke prophylaxis in atrial fibrillation (AF).
This population-based cohort study examined the independent effect of sex on hemorrhage and ischemic stroke in 23,884 patients (55% females; age ≥ 66 years) with AF starting apixaban or rivaroxaban treatment in Ontario, Canada. Patients were followed for 90 days after their DOAC prescription. Using female sex as the exposure of interest, differences in baseline characteristics were balanced between sexes using inverse probability weights based on propensity scores. Applying weighted modified Poisson regression, risk ratios (RRs) were estimated for major hemorrhage, ischemic stroke/systemic embolism/transient ischemic attack (hereafter stroke), myocardial infarction, and all-cause mortality, with males as a reference.
Females were older, had higher predicted stroke risk (based on CHADS score), and had fewer comorbidities than did males. Males had a higher prevalence of coronary artery disease, diabetes, and cancer, and similar predicted bleeding risk (based on HAS-BLED score). After weighting, baseline characteristics were well balanced. The 90-day risks for hemorrhage (RR 0.96; 95% confidence interval [CI] 0.80-1.15; = 0.69) and stroke (RR 1.01; 95% CI 0.86-1.19; = 0.94) were similar between sexes, which remained true when assessing each DOAC separately by dosing regimen. Compared to males, females had a lower risk for myocardial infarction (RR 0.66; 95% CI 0.52-0.84; = 0.0008), and for all-cause mortality (RR 0.76; 95% CI 0.67-0.87; < 0.0001).
Our findings do not suggest an association of sex with the 90-day risk of hemorrhage or ischemic stroke in older AF patients prescribed apixaban or rivaroxaban.
临床试验证据表明，性别对直接口服抗凝剂（DOACs）预防心房颤动（AF）患者中风的有效性和安全性有不同影响。
这项基于人群的队列研究，在加拿大安大略省23884例（55%为女性；年龄≥66岁）开始接受阿哌沙班或利伐沙班治疗的AF患者中，研究了性别对出血和缺血性中风的独立影响。患者在开具DOAC处方后随访90天。以女性为感兴趣的暴露因素，基于倾向评分使用逆概率权重使性别间的基线特征达到平衡。应用加权修正泊松回归，以男性为参照，估计主要出血、缺血性中风/全身性栓塞/短暂性脑缺血发作（以下简称中风）、心肌梗死和全因死亡率的风险比（RRs）。
女性年龄更大，预测的中风风险更高（基于CHADS评分），合并症比男性少。男性冠状动脉疾病、糖尿病和癌症的患病率更高，预测的出血风险相似（基于HAS - BLED评分）。加权后，基线特征得到很好的平衡。性别间出血（RR 0.96；95%置信区间[CI] 0.80 - 1.15；P = 0.69）和中风（RR 1.01；95% CI 0.86 - 1.19；P = 0.94）的90天风险相似，按给药方案分别评估每种DOAC时也是如此。与男性相比，女性心肌梗死风险较低（RR 0.66；95% CI 0.52 - 0.84；P = 0.0008），全因死亡率风险较低（RR 0.76；95% CI 0.67 - 0.87；P < 0.0001）。
我们的研究结果并未表明性别与接受阿哌沙班或利伐沙班治疗的老年AF患者90天出血或缺血性中风风险之间存在关联。
