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Antiplatelet agents for preventing pre‐eclampsia and its complications

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Abstract

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Background

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

Objectives

To assess the effectiveness and safety of antiplatelet agents for women at risk of developing pre‐eclampsia.

Search methods

We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (July 2006), the Cochrane Central Register of Controlled Trials (The Cochrane Library 2005, Issue 1), EMBASE (1994 to November 2005) and handsearched congress proceedings of the International and European Societies for the Study of Hypertension in Pregnancy.

We updated the search of the Cochrane Pregnancy and Childbirth Group's Trials Register on 31 May 2010 and added the results to the awaiting classification section

Selection criteria

All randomised trials comparing antiplatelet agents with either placebo or no antiplatelet agent were included. Quasi‐random studies were excluded. Participants were pregnant women 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.

Data collection and analysis

Two authors assessed trials for inclusion and extracted data independently.

Main results

Fifty‐nine trials (37,560 women) are included. There is a 17% reduction in the risk of pre‐eclampsia associated with the use of antiplatelet agents ((46 trials, 32,891 women, relative risk (RR) 0.83, 95% confidence interval (CI) 0.77 to 0.89), number needed to treat (NNT) 72 (52, 119)). Although there is no statistical difference in RR based on maternal risk, there is a significant increase in the absolute risk reduction of pre‐eclampsia for high risk (risk difference (RD) ‐5.2% (‐7.5, ‐2.9), NNT 19 (13, 34)) compared with moderate risk women (RD ‐0.84 (‐1.37, ‐0.3), NNT 119 (73, 333)).

Antiplatelets were associated with an 8% reduction in the relative risk of preterm birth (29 trials, 31,151 women, RR 0.92, 95% CI 0.88 to 0.97); NNT 72 (52, 119)), a 14% reduction in fetal or neonatal deaths (40 trials, 33,098 women, RR 0.86, 95% CI 0.76 to 0.98); NNT 243 (131, 1,666) and a 10% reduction in small‐for‐gestational age babies (36 trials, 23,638 women, RR 0.90, 95% CI0.83 to 0.98). There were no statistically significant differences between treatment and control groups for any other outcomes.

Authors' conclusions

Antiplatelet agents, largely low‐dose aspirin, have moderate benefits when used for prevention of pre‐eclampsia and its consequences. Further information is required to assess which women are most likely to benefit, when treatment is best started, and at what dose.

[Note: The 16 citations in the awaiting classification section of the review may alter the conclusions of the review once assessed.]

PICOs

Population
Intervention
Comparison
Outcome

The PICO model is widely used and taught in evidence-based health care as a strategy for formulating questions and search strategies and for characterizing clinical studies or meta-analyses. PICO stands for four different potential components of a clinical question: Patient, Population or Problem; Intervention; Comparison; Outcome.

See more on using PICO in the Cochrane Handbook.

Plain language summary

Antiplatelet agents for preventing pre‐eclampsia and its complications

Low doses of aspirin do help prevent pre‐eclampsia, and some of its complications.

Pre‐eclampsia is a condition in pregnancy involving high blood pressure and protein in the urine. It can lead to serious complications. As it affects blood clotting, antiplatelets (drugs like aspirin which can prevent blood clots) are used to prevent pre‐eclampsia. The review of 59 trials, involving 37,560 women, found low doses of aspirin reduced the risk of pre‐eclampsia by about a sixth (17%), with a similar lowering in the risk of the baby dying (14%) and a small lowering in the risk of being born too early (8%). Doses up to 75 mg appear to be safe. Higher doses might be better, but adverse effects may also increase.