Antiplatelet agents for preventing pre-eclampsia and its complications

The six largest studies of the use of antiplatelet agents for the prevention of pre-eclampsia have failed to demonstrate any clinically significant reduction in either pre-eclampsia or fetal or neonatal mortality.

RHL Commentary by Mignini L

1. EVIDENCE SUMMARY

Overall, 59 trials involving 37,560 women are included in this review. For prevention, the use of antiplatelet agents, primary aspirin, was associated with 17 % reduction in the risk of pre-eclampsia [46 trials, 32,891 women, relative risk (RR) 0.83, 95% confidence interval (CI) 0.77 to 0.89], a 14% reduction in fetal or neonatal deaths (40 trials, 33,098 women, RR 0.86; 95% CI 0.76 to 0.98). The reduction in the risk of pre-eclampsia was greater in women at high risk (RR 0.75; 95% CI 0.66 to 0.85) than in women at moderate-risk (RR 0.86; 95% CI 0.79 to 0.95) and in trials evaluating 75 mg/day or more (RR 0.64; 95% CI 0.51 to 0.80) compared with those that evaluated less than 75 mg/day of aspirin (RR 0.88; 95% CI 0.81 to 0.95).These results were consistent regardless of the length of gestation at entry into the trial. There was no effect on the risk of pregnancy-induced hypertension, size of infant for gestational age and placental abruption.

It must be noted that the potential benefits found in this review were mainly supported by small trials, while the bigger ones failed to demonstrate a significant effect in reduction in pre-eclampsia and fetal or neonatal death. These large studies (USA 1993, CLASP 1994, Barbados 1998, Jamaica 1998 USA 1998 and ERASME 2003) recruited more than 26000 women (79 % of the total of women included in the review), so the possibility of publication bias cannot be excluded.

An extensive and appropriate literature search, based on the strategy used by the Pregnancy and Childbirth Group of the Cochrane Collaboration was performed. However, despite this exhaustive search, the funnel plot analysis of the data for pre-eclampsia (data not published in the review) show possible risk of publication bias affecting the review. The methodology used for data extraction, analysis and presentation is sound. There was no attempt to incorporate study quality either in analysis on in generating inferences.

2. RELEVANCE TO UNDER-RESOURCED SETTINGS

2.1. Magnitude of the problem

Hypertensive disorders of pregnancy represent a significant public health problem throughout the world and pre-eclampsia is the most common of these disorders.1 The rate of pre-eclampsia varies between 5 % and 10 % in the developed world, but the figure could be as high as 18 % in some developing countries.2 Pre-eclampsia remains a major cause of maternal and perinatal morbidity and mortality worldwide.3 In some developing countries pre-eclampsia accounts for 40-80 % of maternal deaths.4 Furthermore, perinatal mortality is increased 5-fold in women with pre-eclampsia.5 Increased perinatal mortality is often due to intrauterine growth restriction and preterm deliveries.

2.2. Applicability of the results

The results of this Cochrane review are applicable to under-resourced settings, especially as eleven trials involving more than 12800 women (38.3 % of the total number of women included in this review) took place in developing countries. Moreover, aspirin is inexpensive and easily available in most under-resourced settings.

2.3. Implementation of the intervention

Antiplatelet agents produce moderate but consistent reductions in pre-eclampsia and its consequences. Data from this review suggest that 72 (52 to 119) women need to be treated with aspirin to avoid a single case of pre-eclampsia. This information should be discussed with women at risk of pre-eclampsia to help them make informed choices about their antenatal care. Whether individual women will choose to take antiplatelet agents might depend on an assessment of their absolute risk.

3. RESEARCH

Several questions remain about the role of the administration of low dose of aspirin for prevention of pre-eclampsia or for the improvement of perinatal outcomes. Although, there is promising evidence that higher doses of aspirin may be more effective, this will require careful evaluation as risks may also be increased. Data from individual women of the trials included in this review were recently published6 in order to identify those women most likely to benefit, the gestational age when treatment should start, and optimal dose to be used. Individual data analyses, even when consistent with the systematic review, fail to demonstrate any particular subgroup that could benefit more with this intervention. Until more information become available, decisions about antiplatelets use during pregnancy need to be discussed jointly with women according to there individual risk.

Source of support: Centro Rosarino de Estudios Perinatales, Rosario, Argentina.

References

  • Roberts JM, Pearson G, Cutler J, Lindheimer M. Summary of the NHLBI Working Group on Research on Hypertension During Pregnancy. Hypertension 2003;41:437-45.
  • Sibai BM, Caritis SN, Thom E, Klebanoff M, McNellis D, Rocco L et al. Prevention of preeclampsia with low-dose aspirin in healthy, nulliparous pregnant women. The National Institute of Child Health and Human Development Network of Maternal-Fetal Medicine Units. N.Engl.J Med 1993;329:1213-8.
  • Villar J, Say L, Gulmezoglu AM, Merialdi M, Lindheimer M, Beltran AP et al. Eclampsia and preeclampsia: a worldwide health problem for 2000 years. In Critchley H, Maclean A, Poston L, Walker J, eds. Preeclampsia, London: RCOG, 2003.
  • Sibai BM. Hypertension in pregnancy. Obstet Gynecol Clin North Am 1992;19:615-32.
  • Lain KY,.Roberts JM. Contemporary concepts of the pathogenesis and management of preeclampsia. JAMA 2002;287:3183-6.
  • Askie LM, Duley L, Henderson-Smart DJ, Stewart LA. Antiplatelet agents for prevention of pre-eclampsia: a meta-analysis of individual patient data. Lancet 2007;369:1791-8.

This document should be cited as: Mignini L. Antiplatelet agents for preventing and treating pre-eclampsia: RHL commentary (last revised: 23 June 2007). The WHO Reproductive Health Library; Geneva: World Health Organization.

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