7b The pharmacological prevention of pre-eclampsia

Abstract

The disparate results reported in the literature on the effects of low dose aspirin in preventing pre-eclampsia might be caused by non-compliance in the more recent large trials in low-risk patients. All the earlier small trials were done on identified high-risk patients who consider themselves as patients, as do their doctors. Compliance in these patients will be very high. In fact, the only study in healthy subjects in which aspirin intake was controlled for (Hauth et al 1993) showed a marked reduction in the incidence of pre-eclampsia. However, the recent large trials have demonstrated, without any doubt, that low dose aspirin is not a miracle drug. The combined literature points at a 25% reduction in the incidence of pre-eclampsia in association with the use of aspirin (Collins, 1994). The correct indication for the use of low-dose aspirin appears to be the patient that is at very high risk of developing early-onset (less than 32 weeks gestation) pre-eclampsia. Since early-onset pre-eclampsia can begin at any time after 20 weeks gestation, it is necessary to initiate low-dose aspirin therapy early in pregnancy, preferably at 10-14 weeks gestation. The results of the recent large trials emphasize the need for a reliable, sensitive method of predicting or detecting pre-eclampsia at a very early gestational age (Dekker and Sibai, 1991). Valensise et al (1993) recently confirmed earlier studies (McParland et al, 1990) on the useful combination of uteroplacental Doppler flow velocimetry and aspirin in low-risk primigravidae. Results from current large-scale trials, such as the ECPPA, the BLASP, the WHO Jamaica and the second NICHHD studies, will be available in the near future. The results of especially the second NICHHD study on low-dose aspirin, in more than 2000 high-risk women (previous pre-eclampsia/eclampsia, chronic hypertension, class B to F diabetes or multiple gestation), will hopefully give us a more definitive picture on the potential benificial effects of low-dose aspirin in high-risk patients. The effect of aspirin on placental TXA2 deserves further studies. It might be that the optimal level to inhibit placental TXA2 and lipid peroxide production is actually higher than the minimal effective doses of aspirin that are needed to inhibit platelet TXA2 production (Walsh, 1994). Low-dose aspirin appears to be safe for the fetus and neonate. If there is an increased risk of abruptio placentae, this risk appears to be minimal. The final word on the use of low-dose aspirin has not yet been reached; however, we may be getting closer to profiling patients for whom the therapy may be efficacious and beneficial to both mother and fetus. Further studies are also necessary on combinations of aspirin and other antithrombotic drugs, such as heparin or ketanserin (Tanaka et al, 1993; Bolte et al, 1994; North et al, 1994). North et al (1994) demonstrated that treatment of women with severe renal disease with heparin plus aspirin reduced the prevalence of superimposed pre-eclampsia, compared with no treatment or aspirin alone. Next to low-dose aspirin, there appear to be several new and promising pharmaceutical approaches for reducing the consequences of EC dysfunction. Among these are selective TXA2-synthetase or TXA2-receptor antagonists, Serotonin2-receptor blockers, stable PGI2 analogues and NO donors.