Antiplatelet agents for preventing pre-eclampsia and its complications.
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.


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


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.


METHODS
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.


METHODS
Two authors assessed trials for inclusion and extracted data independently.


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.


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.
Duley
L
L
University of Leeds, Centre for Epidemiology and Biostatistics, Academic Unit, Fieldhouse, Bradford Teaching Hospitals Foundation Trust, Bradford Royal Infirmary, Duckworth Lane, Bradford, West Yorkshire, UK BD9 6RJ. l.duley@leeds.ac.uk
Henderson-Smart
D J
DJ
Meher
S
S
King
J F
JF
D001241:Aspirin / Q000627:therapeutic use; D005260:Female; D005313:Fetal Death / Q000517:prevention & control; D006801:Humans; D007752:Obstetric Labor, Premature / Q000517:prevention & control; D010975:Platelet Aggregation Inhibitors / Q000627:therapeutic use*; D011225:Pre-Eclampsia / Q000517:prevention & control*; D011247:Pregnancy; D016032:Randomized Controlled Trials as Topic
D010975:Platelet Aggregation Inhibitors; D001241:Aspirin