Reason for withdrawal from publication
The 'Antiplatelet agents for preventing and treating pre‐eclampsia' review has been withdrawn because it has been updated by the 2006 updated 'Antiplatelet agents for preventing pre‐eclampsia and its complications' published in The Cochrane Library Issue 2, 2007.
Trials previously classified as 'treatment' rather than 'secondary prevention' (India 1993; India 1994; Israel 1990; subgroup of UK 1992; subgroup of CLASP 1994; subgroup of Italy 1993) in this review are now included with the updated review, but under a different comparison for secondary prevention of pre‐eclampsia.
The editorial group responsible for this previously published document have withdrawn it from publication.
Feedback
Coomarasamy, February 2001
Summary
[Aspirin has clinically significant benefit in high risk groups ‐ Summary NNT can mislead clinicians and women]
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.
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.
Reply
The main aim of our review was to summarise the evidence. We agree the number needed to treat will be more favourable for women at higher risk, nevertheless, women at moderate/low risk do also seem to benefit. The public health benefit of a 15% reduction in pre‐eclampsia and a 14% reduction in stillbirth and neonatal death is difficult to quantify, but is likely to be important. Aspirin is the best we have to offer for prevention of pre‐eclampsia, with the added advantages of being low cost and reasonable reassurance about safety.
As indicated in our review, we are addressing the issue of potential variations in effect size for women with different baseline risk by undertaking a review based on data from individual women.
[reply from the review team, September 2002]
Contributors
Comments by:
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
What's new
| Date | Event | Description |
|---|---|---|
| 20 August 2008 | Amended | Converted to new review format. |
History
Protocol first published: Issue 4, 1997 Review first published: Issue 2, 2000
| Date | Event | Description |
|---|---|---|
| 12 February 2007 | Amended | Review withdrawn from publication in The Cochrane Library 2007, Issue 2. |
Sources of support
Internal sources
NSW Centre for Perinatal Health Services Research, University of Sydney, Australia.
Royal Prince Alfred Hospital, Sydney, Australia.
Perinatal Epidemiology Unit, Mater Hospital, Brisbane, Australia.
External sources
Medical Research Council, UK.
Withdrawn from publication for reasons stated in the review