BACKGROUND: The increased platelet and endothelial thromboxane activity found in patients with preeclampsia can be inhibited by antiplatelet agents such as aspirin. This systematic review tested the hypothesis that antiplatelet drugs can prevent preeclampsia and its complications. Because of a theoretical risk of placental abruption, providers may currently be reluctant to prescribe aspirin in pregnancy.
POPULATION STUDIED: A total of 39 trials enrolling 30,563 women at risk for preeclampsia were identified. Participants were divided into prespecified subgroups: high or moderate risk for developing preeclampsia, before or after 20 weeks’ gestation at randomization, the dose of aspirin less than or equal to 75 mg, and the use of a placebo for the control group. High risk was defined as a history of previous severe preeclampsia, diabetes, chronic hypertension, renal disease, or autoimmune disease. Moderate risk was defined as primigravada, mild hypertension and no proteinurea, positve rollover test, abnormal uterine artery Doppler scan, multiple pregnancies, a family history of severe preeclampsia, and being a teenager. Most studies used aspirin versus placebo, and a minority of trials used other agents that included dipyridamole, heparin, or ozagrel.
STUDY DESIGN AND VALIDITY: The reviewers searched the Register of Trials maintained by the Cochrane Pregnancy and Childbirth Group, the Cochrane Controlled Trials Register, EMBASE, and the proceedings of the International and European Societies for the Study of Hypertension in Pregnancy. Two pairs of reviewers assessed validity independently. Trials were excluded for quasirandomization, such as alternate allocation and if greater than 20% of participants were lost to follow-up or were not reported in the final results.
OUTCOMES MEASURED: The primary outcomes measured were preeclampsia, preterm birth, fetal or neonatal death and small for gestational age. Other outcomes included eclampsia, maternal death, placental abruption, and cesarean delivery.
RESULTS: The use of antiplatelet drugs was associated with a 15% reduction in the risk of preeclampsia (relative risk [RR]=0.85; 95% confidence interval [CI], 0.78-0.92; number needed to treat [NNT]=100). This 15% reduction was consistent across all subgroups except for women receiving more than 75 mg of aspirin (RR=0.35; 95% CI, 0.24-0.52). There was an 8% reduction in the risk of preterm birth (RR=0.92; 95% CI, 0.88-0.97; NNT=72) that was consistent across all subgroups except those receiving more than 75 mg of aspirin (RR=0.58; 95% CI, 0.38-0.88). There was a 14% reduction in the risk of fetal or neonatal death (RR=0.86; 95% CI, 0.75-0.98; NNT=250). There were no significant differences between treatment and control groups in all other outcomes measured, including the risk of placental abruption (RR=1.05; 95% CI, 0.83-1.32).
This systematic review supports antiplatelet therapy for women at moderate to high risk for preeclampsia. Although large numbers of women need to be treated to prevent one adverse outcome, the intervention is inexpensive and safe. Women at risk for preeclampsia should be made aware of this study, and the decision to use aspirin should be made between the patient and physician. Aspirin ( 75 mg) should be used after 16 weeks’ gestation, as this is most consistent with current data on safety. More investigation is needed to identify which subgroups of women might have greater benefit, what dose of aspirin to use, and whether beginning prophylaxis before 12 weeks would be both safe and effective, since this is when faulty implantation of the placenta occurs in preeclampsia.