Antiplatelet agents for preventing pre-eclampsia and its complications

Abstract

Background: Pre-eclampsia is associated with deficient intravascular production of prostacyclin, a vasodilator, and excessive production of thromboxane, a platelet-derived vasoconstrictor and stimulant of platelet aggregation. These observations led to the hypotheses that antiplatelet agents, low-dose aspirin in particular, might prevent or delay the development of pre-eclampsia.

Objectives: To assess the effectiveness and safety of antiplatelet agents when given to women at risk of developing pre-eclampsia.

Search strategy: We searched the Cochrane Pregnancy and Childbirth Group trials register (September 2003), the Cochrane Central Register of Controlled Trials (The Cochrane Library, Issue 2, 2003), EMBASE (1994 to 2003) and we handsearched the congress proceedings of the International and European Societies for the Study of Hypertension in Pregnancy.

Selection criteria: All randomised trials comparing antiplatelet agents with either placebo or no antiplatelet agent during pregnancy. Quasi-random study designs were excluded. Participants were pregnant women considered to be at risk of developing pre-eclampsia. Interventions were any comparisons of an antiplatelet agent (such as low-dose aspirin or dipyridamole) with either placebo or no antiplatelet agent.

Data collection and analysis: Two reviewers assessed trials for inclusion in the review and extracted data. We entered data into the Review Manager software and double checked.

Main results: Fifty-one trials involving 36,500 women are included in this review. There is a 19% reduction in the risk of pre-eclampsia associated with the use of antiplatelet agents ((43 trials, 33,439 women; relative risk (RR) 0.81, 95% confidence interval (CI) 0.75 to 0.88); number needed to treat (NNT) 69 (51, 109)).Twenty-eight trials (31,845 women) reported preterm birth. There is a small (7%) reduction in the risk of delivery before 37 completed weeks ((RR 0.93, 95% CI 0.89 to 0.98); NNT 83 (50, 238)). Fetal or neonatal deaths were reported in 38 trials (34,010 women). Overall there is a 16% reduction in baby deaths in the antiplatelet group (RR 0.84, 95% CI 0.74 to 0.96); NNT 227 (128, 909)). Small-for-gestational age babies were reported in 32 trials (24,310 women), with an 8% reduction in risk (RR 0.92, 95% CI 0.85 to 1.00). There were no significant differences between treatment and control groups in any other measures of outcome.

Reviewer's conclusions: Antiplatelet agents, in this review largely low-dose aspirin, have small-moderate benefits when used for prevention of pre-eclampsia. Further information is required to assess which women are most likely to benefit, when treatment is best started, and at what dose.