Wright David, Poon Liona C, Rolnik Daniel L, Syngelaki Argyro, Delgado Juan Luis, Vojtassakova Denisa, de Alvarado Mercedes, Kapeti Evgenia, Rehal Anoop, Pazos Andrea, Carbone Ilma Floriana, Dutemeyer Vivien, Plasencia Walter, Papantoniou Nikos, Nicolaides Kypros H
University of Exeter, Exeter, United Kingdom.
King's College Hospital, London, United Kingdom; Chinese University of Hong Kong, Hong Kong.
Am J Obstet Gynecol. 2017 Dec;217(6):685.e1-685.e5. doi: 10.1016/j.ajog.2017.08.110. Epub 2017 Sep 6.
The Aspirin for Evidence-Based Preeclampsia Prevention trial was a multicenter study in women with singleton pregnancies. Screening was carried out at 11-13 weeks' gestation with an algorithm that combines maternal factors and biomarkers (mean arterial pressure, uterine artery pulsatility index, and maternal serum pregnancy-associated plasma protein A and placental growth factor). Those with an estimated risk for preterm preeclampsia of >1 in 100 were invited to participate in a double-blind trial of aspirin (150 mg/d) vs placebo from 11-14 until 36 weeks' gestation. Preterm preeclampsia with delivery at <37 weeks' gestation, which was the primary outcome, occurred in 1.6% (13/798) participants in the aspirin group, as compared with 4.3% (35/822) in the placebo group (odds ratio in the aspirin group, 0.38; 95% confidence interval, 0.20 to 0.74).
We sought to examine the influence of compliance on the beneficial effect of aspirin in prevention of preterm preeclampsia in the Aspirin for Evidence-Based Preeclampsia Prevention trial.
This was a secondary analysis of data from the trial. The proportion of prescribed tablets taken was used as an overall measure of compliance. Logistic regression analysis was used to estimate the effect of aspirin on the incidence of preterm preeclampsia according to compliance of <90% and ≥90%, after adjustment for the estimated risk of preterm preeclampsia at screening and the participating center. The choice of cut-off of 90% was based on an exploratory analysis of the treatment effect. Logistic regression analysis was used to investigate predictors of compliance ≥90% among maternal characteristics and medical history.
Preterm preeclampsia occurred in 5/555 (0.9%) participants in the aspirin group with compliance ≥90%, in 8/243 (3.3%) of participants in the aspirin group with compliance <90%, in 22/588 (3.7%) of participants in the placebo group with compliance ≥90%, and in 13/234 (5.6%) of participants in the placebo group with compliance <90%. The odds ratio in the aspirin group for preterm preeclampsia was 0.24 (95% confidence interval, 0.09-0.65) for compliance ≥90% and 0.59 (95% confidence interval, 0.23-1.53) for compliance <90%. Compliance was positively associated with family history of preeclampsia and negatively associated with smoking, maternal age <25 years, Afro-Caribbean and South Asian racial origin, and history of preeclampsia in a previous pregnancy.
The beneficial effect of aspirin in the prevention of preterm preeclampsia appears to depend on compliance.
基于证据的子痫前期预防阿司匹林试验是一项针对单胎妊娠女性的多中心研究。在妊娠11至13周时进行筛查，采用一种结合母体因素和生物标志物（平均动脉压、子宫动脉搏动指数以及母体血清妊娠相关血浆蛋白A和胎盘生长因子）的算法。那些早产子痫前期估计风险大于1/100的孕妇被邀请参加一项双盲试验，从妊娠11至14周直至36周，服用阿司匹林（150毫克/天）或安慰剂。主要结局为妊娠<37周时发生的早产子痫前期，阿司匹林组1.6%（13/798）的参与者出现该情况，而安慰剂组为4.3%（35/822）（阿司匹林组的比值比为0.38；95%置信区间为0.20至0.74）。
我们试图在基于证据的子痫前期预防阿司匹林试验中，研究依从性对阿司匹林预防早产子痫前期有益效果的影响。
这是对该试验数据的二次分析。所服用规定药片的比例用作依从性的总体衡量指标。在对筛查时早产子痫前期的估计风险和参与中心进行调整后，采用逻辑回归分析来估计根据依从性<90%和≥90%时阿司匹林对早产子痫前期发生率的影响。选择90%作为临界值是基于对治疗效果的探索性分析。采用逻辑回归分析来研究母体特征和病史中依从性≥90%的预测因素。
阿司匹林组中依从性≥90%的5/555（0.9%）参与者发生了早产子痫前期，依从性<90%的8/243（3.3%）参与者发生了该情况；安慰剂组中依从性≥90%的22/588（3.7%）参与者发生了早产子痫前期，依从性<90%的13/234（5.6%）参与者发生了该情况。阿司匹林组中依从性≥90%时早产子痫前期的比值比为0.24（95%置信区间为0.09 - 0.65），依从性<90%时为0.59（95%置信区间为0.23 - 1.53）。依从性与子痫前期家族史呈正相关，与吸烟、母亲年龄<25岁、非洲 - 加勒比和南亚种族出身以及既往妊娠子痫前期病史呈负相关。
阿司匹林预防早产子痫前期的有益效果似乎取决于依从性。
