Advertisement

Aspirin for Evidence-Based Preeclampsia Prevention trial: influence of compliance on beneficial effect of aspirin in prevention of preterm preeclampsia

Published:September 06, 2017DOI:https://doi.org/10.1016/j.ajog.2017.08.110

      Background

      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).

      Objective

      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.

      Study Design

      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.

      Results

      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.

      Conclusion

      The beneficial effect of aspirin in the prevention of preterm preeclampsia appears to depend on compliance.

      Key words

      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'

      Subscribe:

      Subscribe to American Journal of Obstetrics & Gynecology
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect

      References

        • Meher S.
        • Duley L.
        • Hunter K.
        • Askie L.
        Antiplatelet therapy before or after 16 weeks’ gestation for preventing preeclampsia: an individual participant data meta-analysis.
        Am J Obstet Gynecol. 2017; 216: 121-128
        • Roberge S.
        • Nicolaides K.
        • Demers S.
        • Hyett J.
        • Chaillet N.
        • Bujold E.
        The role of aspirin dose on the prevention of preeclampsia and fetal growth restriction: systematic review and meta-analysis.
        Am J Obstet Gynecol. 2017; 216: 110-120.e1-6
        • Rolnik D.L.
        • Wright D.
        • Poon L.C.
        • et al.
        Aspirin versus placebo in pregnancies at high risk for preterm preeclampsia.
        N Engl J Med. 2017; 77: 613-622
        • Akolekar R.
        • Syngelaki A.
        • Poon L.
        • Wright D.
        • Nicolaides K.H.
        Competing risks model in early screening for preeclampsia by biophysical and biochemical markers.
        Fetal Diagn Ther. 2013; 33: 8-15
        • Coronary Drug Project Research Group
        Influence of adherence to treatment and response of cholesterol on mortality in the coronary drug project.
        N Engl J Med. 1980; 303: 1038-1041
        • Manninen V.
        • Elo M.O.
        • Frick M.H.
        • et al.
        Lipid alterations and decline in the incidence of coronary heart disease in the Helsinki Heart Study.
        JAMA. 1988; 260: 641-651
        • Cramer J.A.
        Effect of partial compliance on cardiovascular medication effectiveness.
        Heart. 2002; 88: 203-206
        • Cramer J.A.
        • Benedict A.
        • Muszbek N.
        • Keskinaslan A.
        • Khan Z.M.
        The significance of compliance and persistence in the treatment of diabetes, hypertension and dyslipidemia: a review.
        Int J Clin Pract. 2008; 62: 76-87
        • Simpson S.H.
        • Eurich D.T.
        • Majumdar S.R.
        • et al.
        A meta-analysis of the association between adherence to drug therapy and mortality.
        BMJ. 2006; 333: 15
        • Shingler S.L.
        • Bennett B.M.
        • Cramer J.A.
        • Towse A.
        • Twelves C.
        • Lloyd A.J.
        Treatment preference, adherence and outcomes in patients with cancer: literature review and development of a theoretical model.
        Curr Med Res Opin. 2014; 30: 2329-2341
        • Romero R.
        • Erez O.
        • Hüttemann M.
        • et al.
        Metformin, the aspirin of the 21st century: its role in gestational diabetes mellitus, prevention of preeclampsia and cancer, and the promotion of longevity.
        Am J Obstet Gynecol. 2017; 217: 282-302
        • Wright D.
        • Syngelaki A.
        • Akolekar R.
        • Poon L.C.
        • Nicolaides K.H.
        Competing risks model in screening for preeclampsia by maternal characteristics and medical history.
        Am J Obstet Gynecol. 2015; 213: 62.e1-62.e10
        • Poon L.C.
        • Zymeri N.A.
        • Zamprakou A.
        • Syngelaki A.
        • Nicolaides K.H.
        Protocol for measurement of mean arterial pressure at 11-13 weeks' gestation.
        Fetal Diagn Ther. 2012; 31: 42-48
        • Plasencia W.
        • Maiz N.
        • Bonino S.
        • Kaihura C.
        • Nicolaides K.H.
        Uterine artery Doppler at 11+0 to 13+6 weeks in the prediction of pre-eclampsia.
        Ultrasound Obstet Gynecol. 2007; 30: 742-749
        • Wright A.
        • Wright D.
        • Ispas A.
        • Poon L.C.
        • Nicolaides K.H.
        Mean arterial pressure in the three trimesters of pregnancy: effects of maternal characteristics and medical history.
        Ultrasound Obstet Gynecol. 2015; 45: 698-706
        • Tayyar A.
        • Guerra L.
        • Wright A.
        • Wright D.
        • Nicolaides K.H.
        Uterine artery pulsatility index in the three trimesters of pregnancy: effects of maternal characteristics and medical history.
        Ultrasound Obstet Gynecol. 2015; 45: 689-697
        • Wright D.
        • Silva M.
        • Papadopoulos S.
        • Wright A.
        • Nicolaides K.H.
        Serum pregnancy associated plasma protein-A in the three trimesters of pregnancy: effects of maternal characteristics and medical history.
        Ultrasound Obstet Gynecol. 2015; 46: 42-50
        • Tsiakkas A.
        • Duvdevani N.
        • Wright A.
        • Wright D.
        • Nicolaides K.H.
        Serum placental growth factor in the three trimesters of pregnancy: effects of maternal characteristics and medical history.
        Ultrasound Obstet Gynecol. 2015; 45: 591-598
        • Robinson H.P.
        • Fleming J.E.
        A critical evaluation of sonar crown rump length measurements.
        Br J Obstet Gynaecol. 1975; 82: 702-710
        • Brown M.A.
        • Lindheimer M.D.
        • de Swiet M.
        • Van Assche A.
        • Moutquin J.M.
        The classification and diagnosis of the hypertensive disorders of pregnancy: statement from the International Society for the Study of Hypertension in Pregnancy (ISSHP).
        Hypertens Pregnancy. 2001; 20: IX-XIV
        • R Development Core Team
        R: a language and environment for statistical computing.
        R Foundation for Statistical Computing, Vienna (Austria)2011
        • Navaratnam K.
        • Alfirevic A.
        • Alfirevic Z.
        Low dose aspirin and pregnancy: how important is aspirin resistance?.
        BJOG. 2016; 123: 1481-1487
        • Breckenridge A.
        • Aronson J.K.
        • Blaschke T.F.
        • Hartman D.
        • Peck C.C.
        • Vrijens B.
        Poor medication adherence in clinical trials: consequences and solutions.
        Nat Rev Drug Discov. 2017; 16: 149-150

      Linked Article

      • November 2017 (vol. 217, no. 5, page 586)
        American Journal of Obstetrics & GynecologyVol. 218Issue 4
        • Preview
          Poon LC, Wright D, Rolnik DL, et al. Aspirin for Evidence-Based Preeclampsia Prevention trial: effect of aspirin in prevention of preterm preeclampsia in subgroups of women according to their characteristics and medical and obstetrical history. Am J Obstet Gynecol 2017;217:585.e1-5.
        • Full-Text
        • PDF