David Wright1, Liona C Poon2, Daniel L Rolnik3, Argyro Syngelaki3, Juan Luis Delgado4, Denisa Vojtassakova5, Mercedes de Alvarado6, Evgenia Kapeti7, Anoop Rehal8, Andrea Pazos9, Ilma Floriana Carbone10, Vivien Dutemeyer11, Walter Plasencia12, Nikos Papantoniou13, Kypros H Nicolaides14. 1. University of Exeter, Exeter, United Kingdom. 2. King's College Hospital, London, United Kingdom; Chinese University of Hong Kong, Hong Kong. 3. King's College Hospital, London, United Kingdom. 4. Hospital Clínico Universitario Virgen de la Arrixaca, Murcia, Spain. 5. King's College Hospital, London, United Kingdom; Medway Maritime Hospital, Gillingham, United Kingdom. 6. King's College Hospital, London, United Kingdom; Homerton University Hospital, London, United Kingdom. 7. King's College Hospital, London, United Kingdom; North Middlesex University Hospital, London, United Kingdom. 8. King's College Hospital, London, United Kingdom; Southend University Hospital, Essex, United Kingdom. 9. Hospital Universitario San Cecilio, Granada, Spain. 10. Ospedale Maggiore Policlinico, Milan, Italy. 11. University Hospital Brugmann, Université Libre de Bruxelles, Brussels, Belgium. 12. Hospiten Group, Tenerife, Canary Islands, Spain. 13. Attikon University Hospital, Athens, Greece. 14. King's College Hospital, London, United Kingdom. Electronic address: kypros@fetalmedicine.com.
Abstract
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.
RCT Entities:
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.
Authors: Liona C Poon; Andrew Shennan; Jonathan A Hyett; Anil Kapur; Eran Hadar; Hema Divakar; Fionnuala McAuliffe; Fabricio da Silva Costa; Peter von Dadelszen; Harold David McIntyre; Anne B Kihara; Gian Carlo Di Renzo; Roberto Romero; Mary D'Alton; Vincenzo Berghella; Kypros H Nicolaides; Moshe Hod Journal: Int J Gynaecol Obstet Date: 2019-05 Impact factor: 3.561
Authors: Hannah E Laue; Raphael Cassoulet; Nadia Abdelouahab; Yasmine K Serme-Gbedo; Anne-Sandrine Desautels; Kasey J M Brennan; Jean-Philippe Bellenger; Heather H Burris; Brent A Coull; Marc G Weisskopf; Larissa Takser; Andrea A Baccarelli Journal: Toxicol Sci Date: 2019-01-01 Impact factor: 4.849
Authors: Liona C Poon; Laura A Magee; Stefan Verlohren; Andrew Shennan; Peter von Dadelszen; Eyal Sheiner; Eran Hadar; Gerard Visser; Fabricio Da Silva Costa; Anil Kapur; Fionnuala McAuliffe; Amala Nazareth; Muna Tahlak; Anne B Kihara; Hema Divakar; H David McIntyre; Vincenzo Berghella; Huixia Yang; Roberto Romero; Kypros H Nicolaides; Nir Melamed; Moshe Hod Journal: Int J Gynaecol Obstet Date: 2021-07 Impact factor: 4.447