背景:在美国,领先的医学协会建议每天服用81毫克阿司匹林,以预防处于危险中的女性先兆子痫(PE),而英国的NICE指南推荐剂量高达150mg的阿司匹林.最近的数据还表明,在肥胖人群中,剂量不足或阿司匹林抵抗可能会影响目前推荐剂量的阿司匹林疗效.
目的:我们评估了在高危肥胖孕妇中,每日服用162mg阿司匹林是否比81mg阿司匹林更有效地降低具有严重特征的PE的发生率。
方法:我们在2019年5月至2022年11月之间进行了一项随机试验。12至20周胎龄(GA)的个体,在招募时BMI≥30kg/m2,和三个高危因素中的至少一个:怀孕前的PE病史,至少在妊娠指数中记录了I期高血压,孕前糖尿病或在20周之前诊断为妊娠糖尿病,随机分为每日162mg或81mg阿司匹林,直至分娩。参与者对治疗分配没有盲化.排除标准为:多胎妊娠,已知的主要胎儿畸形,癫痫症,基线蛋白尿,由于其他适应症,服用阿司匹林,或阿司匹林的禁忌症。主要结局是具有严重特征的PE(PE或具有严重特征的叠加PE,子痫,或帮助)。次要结局包括PE导致的早产率,小于胎龄(SGA),产后出血,早剥,和药物副作用。使用对主要结果的预先计划的贝叶斯分析,需要220的样本量,以中性信息先验估计受益或损害的后验概率。
结果:在343名符合条件的个人中,220例(64.1%)随机分组。主要结果为209/220(95%)。组间基线特征相似,纳入研究时,162mg阿司匹林组为15.9周,81mg阿司匹林组为15.6周.16周前的登记发生在55/110分配到162mg和58/110分配到81mg阿司匹林。162mg阿司匹林组的主要结局为35%,81mg阿司匹林组的主要结局为40%(后相对风险,0.88;95%可信区间,0.64-1.22)。贝叶斯分析表明,与81mg阿司匹林剂量相比,162mg阿司匹林降低主要结局的概率为78%。由于先兆子痫引起的指示早产率(21%vs21%),SGA(6.5%对2.9%),两组之间的早剥(2.8%vs3.0%)和产后出血(10%vs8.8%)相似。药物不良反应也相似。
结论:在高危肥胖个体中,有78%的获益概率是162mg阿司匹林与81mg阿司匹林相比可降低具有严重特征的PE的发生率.在该人群中使用162mg阿司匹林与81mg阿司匹林相比,最佳估计减少了12%。此试验支持进行更大的多中心试验。
BACKGROUND: In the United States, leading medical societies recommend 81 mg of aspirin daily for the prevention of preeclampsia (PE) in women at risk, whereas the NICE guidelines in the UK recommend a dose as high as 150 mg of aspirin. Recent data also suggest that in the obese population, inadequate dosing or aspirin resistance may impact the efficacy of aspirin at the currently recommend doses.
OBJECTIVE: We evaluated whether daily administration of 162 mg aspirin would be more effective compared to 81 mg in decreasing the rate of PE with severe features in high-risk obese pregnant individuals.
METHODS: We performed a randomized trial between May 2019 and November 2022. Individuals at 12 to 20-weeks gestational age (GA) with a BMI ≥ 30 kg/m2 at time to enrollment, and at least one of three high risk factors: history of PE in a prior pregnancy, at least stage I hypertension documented in the index pregnancy, pre-gestational diabetes or gestational diabetes diagnosed prior to 20 weeks GA were randomized to either 162 mg or 81 mg of aspirin daily till delivery, participants were not blinded to treatment allocation. Exclusion criteria were: multifetal
gestation, known major fetal anomalies, seizure disorder, baseline proteinuria, on aspirin due to other indications, or contraindication to aspirin. The primary outcome was PE with severe features (PE or superimposed PE with severe features, eclampsia, or HELLP). Secondary outcomes included rates of preterm birth due to PE, small for gestational age (SGA), postpartum hemorrhage, abruption, and medication side effects. A sample size of 220 was needed using a preplanned Bayesian analysis of the primary outcome to estimate the posterior probability of benefit or harm with a neutral informative prior.
RESULTS: Of 343 eligible individuals, 220 (64.1%) were randomized. The primary outcome was available for 209/220 (95%). Baseline characteristics were similar between groups, median gestational age at enrollment was 15.9 weeks in the 162 mg aspirin group and 15.6 weeks in the 81 mg aspirin group. Enrollment prior to 16 weeks occurred in 55/110 of those assigned to 162 mg and 58/110 of those assigned to 81 mg of aspirin. The primary outcome occurred in 35% in the 162 mg aspirin group and in 40% in the 81 mg aspirin group (posterior relative risk, 0.88; 95% credible interval, 0.64-1.22). Bayesian analysis indicated a 78% probability of a reduction in the primary outcome with 162 mg aspirin compared to 81 mg aspirin dose. Rates of indicated preterm birth due to preeclampsia (21% vs 21%), SGA (6.5% vs 2.9%), abruption (2.8% vs 3.0%) and postpartum hemorrhage (10% vs 8.8%) were similar between groups. Medication adverse effects were also similar.
CONCLUSIONS: Among high-risk obese individuals, there was 78% probability of benefit that 162 mg aspirin compared to 81 mg will decrease the rate of PE with severe features. With a best estimate of a 12% reduction when using 162 mg of aspirin in comparison to 81 mg of aspirin in this population. This trial supports doing a larger multicenter trial.