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Meta-Analysis
. 2021 Mar 9;16(3):e0247782.
doi: 10.1371/journal.pone.0247782. eCollection 2021.

Dose of aspirin to prevent preterm preeclampsia in women with moderate or high-risk factors: A systematic review and meta-analysis

Rachel Van Doorn  1 , Narmin Mukhtarova  2 , Ian P Flyke  1 , Michael Lasarev  3 , KyungMann Kim  3 , Charles H Hennekens  4 , Kara K Hoppe  2
Affiliations
Meta-Analysis

Dose of aspirin to prevent preterm preeclampsia in women with moderate or high-risk factors: A systematic review and meta-analysis

Rachel Van Doorn et al. PLoS One. .

Abstract

Objective: To evaluate the effect of aspirin dose on the incidence of all gestational age preeclampsia and preterm preeclampsia.

Data sources: Electronic databases (Cochrane, PubMed, Scopus, ClinicalTrials.gov and the Web of Science) were searched for articles published between January 1985 and March 2019 with no language restrictions.

Methods: We followed the PRIMSA guidelines and utilized Covidence software. Articles were screened by 2 independent reviewers, with discrepancies settled by an independent 3rd party. Study selection criteria were randomized trials comparing aspirin for prevention of all gestational age and preterm preeclampsia to placebo or no antiplatelet treatment in women aged 15-55 years with moderate or high-risk factors according to the list of risk factors from American College of Obstetricians and Gynecologists and United States Preventive Services Task Force guidelines. The quality of trials was assessed using the Cochrane risk of bias tool. The data were pooled using a random-effects meta-analysis comparing aspirin at doses of <81, 81, 100, and 150 mg. Pre-specified outcomes were all gestational age and preterm preeclampsia.

Results: Of 1,609 articles screened, 23 randomized trials, which included 32,370 women, fulfilled the inclusion criteria. In preterm preeclampsia, women assigned at random to 150 mg experienced a significant 62% reduction in risk of preterm preeclampsia (RR = 0.38; 95% CI: 0.20-0.72; P = 0.011). Aspirin doses <150 mg produced no significant reductions. The number needed to treat with 150 mg of aspirin was 39 (95% CI: 23-100). There was a maximum 30% reduction in risk of all gestational age preeclampsia at all aspirin doses.

Conclusions: In this meta-analysis, based on indirect comparisons, aspirin at a dose greater than the current, recommended 81 mg was associated with the highest reduction in preterm preeclampsia. Our meta-analysis is limited due to the deficiency of homogeneous high evidence data available in the literature to date; however, it may be prudent for clinicians to consider that the optimal aspirin dose may be higher than the current guidelines advise. Future research to compare the efficacy aspirin doses greater than 81 mg is recommended.

Study registration: PROSPERO, CRD42019127951 (University of York, UK; http://www.crd.york.ac.uk/PROSPERO/).

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Conflict of interest statement

Drs. Van Doorn, Mukhtarova, Flyke, Lasarev, and Hoppe have no disclosures. Professor Kim reports that he serves as a member of data monitoring committees for Astellas, AstraZeneca, Actelion, Bayer, Bristol-Myers Squibb, GlaxoSmithKline, Idorsia, Merck, and Sarepta. He holds no stock in any biopharmaceutical or medical device company. Professor Hennekens reports that he serves as an independent scientist in an advisory role to investigators and sponsors as Chair of data monitoring committees for Amgen, British Heart Foundation, Cadila, Canadian Institutes of Health Research, DalCor, and Regeneron; to the United States (U.S.) Food and Drug Administration, and UpToDate; receives royalties for authorship or editorship of 3 textbooks and as co-inventor on patents for inflammatory markers and cardiovascular disease that are held by Brigham and Women’s Hospital; has an investment management relationship with the West-Bacon Group within SunTrust Investment Services, which has discretionary investment Cover Letter with amended statements authority; does not own any common or preferred stock in any pharmaceutical or medical device company. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

Figures

Fig 1
Fig 1. PRISMA flow chart: Summary of article search, selection, and exclusion.
Fig 2
Fig 2. Forest plot of the effect of aspirin on the all gestational age preeclampsia outcome stratified by two groups of aspirin doses: At most 81 mg and more than 81 mg.
RR, risk ratio; CI, confidence interval. Black diamond indicates the weight of each study; blue diamond indicates the overall effect of pooled sample; horizontal line indicates 95% confidence interval; solid vertical line indicates no effect.
Fig 3
Fig 3. Forest plot of the effect of aspirin on the all gestational age preeclampsia outcome stratified by four groups of aspirin dose: 36–80 mg, 81 mg, 100 mg, and 150 mg.
RR, risk ratio; CI, confidence interval. Black diamond indicates the weight of each study; blue diamond indicates the overall effect of pooled sample; horizontal line indicates 95% confidence interval; solid vertical line indicates no effect.
Fig 4
Fig 4. Forest plot of the effect of aspirin on the preterm preeclampsia outcome stratified by four groups of aspirin doses: 36–80 mg, 81 mg, 100 mg, and 150 mg.
RR, risk ratio; CI, confidence interval. Black diamond indicates the weight of each study; blue diamond indicates the overall effect of pooled sample; horizontal line indicates 95% confidence interval; solid vertical line indicates no effect.
Fig 5
Fig 5. Forest plot of the effect of all aspirin doses on the all gestational age preeclampsia outcome.
RR, risk ratio; CI, confidence interval. Black diamond indicates the weight of each study; blue diamond indicates the overall effect of pooled sample; horizontal line indicates 95% confidence interval; solid vertical line indicates no effect.
Fig 6
Fig 6. Forest plot of the effect of all aspirin doses on the preterm preeclampsia outcome.
RR, risk ratio; CI, confidence interval. Black diamond indicates the weight of each study; blue diamond indicates the overall effect of pooled sample; horizontal line indicates 95% confidence interval; solid vertical line indicates no effect.
Fig 7
Fig 7. Forest plot of the effect aspirin on the preterm preeclampsia outcome stratified by two groups of aspirin doses: At most 81 mg and more than 81 mg.
RR, risk ratio; CI, confidence interval. Black diamond indicates the weight of each study; blue diamond indicates the overall effect of pooled sample; horizontal line indicates 95% confidence interval; solid vertical line indicates no effect.
See this image and copyright information in PMC

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