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PAPERS: Lelia Duley, David Henderson-Smart, Marian Knight, and James King Antiplatelet drugs for prevention of pre-eclampsia and its consequences: systematic review BMJ 2001; 322: 329-333 [Abstract] [Full text]

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Clinically useful presentation of results

Deirdre J Murphy   (19 February 2001)

Aspirin has clinically significant benefit in high risk groups - Summary NNT can mislead clinicians

A Coomarasamy   (21 February 2001)

Clinically useful presentation of results 19 February 2001
Deirdre J Murphy, Consultant Senior Lecturer in Maternal Medicine University of Bristol Send response to journal: Re: Clinically useful presentation of results	Dear Sir, It is interesting to see the issue of aspirin and pre-eclampsia revisited despite a large number of previously published mega-trials and systematic reviews on this subject 1. What is refreshing about the most recent review is the presentation of efficacy in terms of percentage benefit. This is likely to be clinically useful in the context of pre- pregnancy counselling or post-pregnancy counselling with a view to management in future pregnancies. Therapeutic trials for pre-eclampsia prevention have been limited by an approach that assumed that a single agent would have the potential to reduce the risk of pre-eclampsia to a great extent on a population basis and great disappointment when such has not been the case. What is becoming increasingly apparent is that pre- eclampsia is probably only an umbrella term for a disorder of multiple underlying aetiologies and that no single agent can hope to target such a widespread group of disorders. This can be seen in terms of the associations between thrombophilias, hyperhomocystinaemia, autoimmune disease, antiphospholipid antibody syndrome, and high maternal serum alphafeto protein and pre-eclampsia. This is borne out by a variety of trials demonstrating reductions in the risk of pre-eclampsia with a wide variety of agents - aspirin, other anti-platelet agents, calcium supplements, nitric oxide, fish oils, and more recently antioxidants 2. The report by Duley et al suggests that a 15% reduction in the risk of pre-eclampsia can be achieved with aspirin and more importantly, that there is a 14% reduction in the risk of fetal or neonatal death. It is likely that this reduction is related to efficacy among a subgroup of women where thromboxane/ prostacyclin imbalance is at play. It is important that we recognise the diversity of mechanisms underlying pre- eclampsia and focus parallel research initiatives into both potential therapeutic agents and the underlying aetiologies that are targeted by these agents. Unfortunately such an approach is only likely to be clinically useful for women with a previous history of pre-eclampsia as it would not be cost-effective to screen the entire primiparous population for all potential aetiologies for pre-eclampsia. In the meantime it is clinically helpful to present the potential benefits of any agent in percentage terms, as demonstrated by Duley et al. Clinicians are then in a position to advise women on the potential benefits and risks of taking a specific medication in pregnancy on a prophylactic basis. 1. Duley L, Henderson-Smart D, Knight M, King J. Antiplatelet drugs for prevention of pre-eclampsia and its consequences: systematic review. BMJ 2001;322:329-33. 2. Chappell LC, Seed PT, Briley AL, Kelly FJ et al. Effect of antioxidants on the occurrence of pre-eclampsia in women at increased risk: a randomised trial. Lancet 1999;354:810-16. Deirdre J Murphy MD MRCOG Consultant Senior Lecturer in Maternal Medicine University of Bristol St Michael's Hospital, Southwell St, Bristol BS2 8EG
Aspirin has clinically significant benefit in high risk groups - Summary NNT can mislead clinicians 21 February 2001
A Coomarasamy, Research Fellow in Obstetrics Birmingham Womens Hospital Send response to journal: Re: Aspirin has clinically significant benefit in high risk groups - Summary NNT can mislead clinicians	Editor – The systematic review(1;2) of antiplatelet drugs for prevention of pre-eclampsia found statistically significant reduction in pre-eclampsia and other outcomes such as fetal or neonatal death. The authors concluded that the benefit was ‘small to moderate’ and the implication for practice was that ‘relatively large numbers of women will need to be treated to prevent a single adverse outcome’. With the numbers of women needed to be treated to prevent one case of pre-eclampsia reported as 100 (95% CI 59 to 167), clinicians (and women) might not think treatment worthwhile. However, calculating numbers needed to treat from pooled meta- analysis data may be inappropriate, if it is possible to identify subgroups of patients with substantially differing baseline risks(3). In women with high levels of baseline risk, and assuming constant relative risk from treatment, numbers needed to treat are smaller(4), and both clinicians and women may be much more likely to wish to use aspirin to prevent pre-eclampsia. It has been suggested(1;2) that meta-analysis of individual patient data would be useful both in identifying high-risk subgroups, and estimating the benefit they derive from antiplatelet treatment. However, such meta-analyses generally take a long time to complete(5). What should clinicians do in the mean time? We can see no reason for thinking that the reduction in relative risk for various risk levels will be substantially different. If high-risk (or low risk) women can be identified, by any means, specific numbers needed to treat can then be generated by using pooled relative risk estimates from reviews of effectiveness(4), making the decision to treat (or not) more appropriate and, in this particular case, probably more clear-cut for most women. We systematically reviewed the accuracy of uterine artery Doppler in early pregnancy for predicting pre-eclampsia(6). In clinically high-risk women, a positive Doppler result (abnormal flow velocimetry ratio or the presence diastolic notch) meant a 23.5% (95% CI 18.6 to 29.2) risk of developing pre-eclampsia. With baseline risk elevated to this level and assuming the global estimated relative risk of 0.85(1), we estimate that 31 (95% CI 18 to 55) patients will be needed to be treated with aspirin to prevent one case of pre-eclampsia. We would thus expect most women with abnormal uterine artery Dopplers, when advised by their clinicians, to request antiplatelet treatment. A Coomarasamy Research Fellow in Obstetrics Education Resource Centre, Birmingham Women's Hospital, Metchley Park Road, Birmingham B15 2TG arricoomar@hotmail.com Harry Gee Consultant Obstetrician Birmingham Women's Hospital, B15 2TG Khalid S Khan Consultant Obstetrician and Gynaecologist Birmingham Women's Hospital, B15 2TG David Braunholtz Senior Research Fellow Department of Public Health & Epidemiology, Public Health Building, University of Birmingham, B15 2TT 1. Duley L, Henderson-Smart DJ, Knight M, King JF. Anteplatelet drugs for prevention of pre-eclampsia and its consequences: systematic review. BMJ 2001;322: 329-333.. 2. Knight M, Duley L, Henderson-Smart DJ, King JF. Antiplatelet agents for preventing and treating pre-eclampsia. Cochrane Database.Syst.Rev. 2000;CD000492. 3. Smeeth L, Haines A, Ebrahim S. Numbers needed to treat derived from meta-analyses--sometimes informative, usually misleading. BMJ 1999;318:1548-51. 4. Guyatt GH, Sackett DL, Sinclair JC, Hayward R, Cook DJ, Cook RJ. Users' guides to the medical literature. IX. A method for grading health care recommendations. Evidence-Based Medicine Working Group. JAMA 1995;274:1800-4. 5. Stewart LA,.Clarke MJ. Practical methodology of meta-analyses (overviews) using updated individual patient data. Cochrane Working Group. Stat.Med. 1995;14:2057-79. 6. Chien PF, Arnott N, Gordon A, Owen P, Khan KS. How useful is uterine artery Doppler flow velocimetry in the prediction of pre- eclampsia, intrauterine growth retardation and perinatal death? An overview. BJOG. 2000;107:196-208.