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European Heart Journal Advance Access originally published online on July 3, 2008
European Heart Journal 2008 29(16):2031-2041; doi:10.1093/eurheartj/ehn299
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Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2008. For permissions please email: journals.permissions@oxfordjournals.org
The online version of this article has been published under an open access model. Users are entitled to use, reproduce, disseminate, or display the open access version of this article for non-commercial purposes provided that the original authorship is properly and fully attributed; the Journal, Learned Society and Oxford University Press are attributed as the original place of publication with correct citation details given; if an article is subsequently reproduced or disseminated not in its entirety but only in part or as a derivative work this must be clearly indicated. For commercial re-use, please contact journals.permissions@oxfordjournals.org.

Association between hormone replacement therapy and subsequent arterial and venous vascular events: a meta-analysis

Gillian M. Sare, Laura J. Gray and Philip M.W. Bath*

Stroke Trials Unit, Institute of Neuroscience, University of Nottingham, Nottingham, UK

Received 31 March 2008; revised 9 June 2008; accepted 11 June 2008; online publish-ahead-of-print 3 July 2008.

* Corresponding author. Tel: +44 115 823 1768, Fax: +44 115 823 1767, Email: philip.bath{at}nottingham.ac.uk

Aims: Randomized controlled trials (RCTs) have shown that the risk of stroke and venous thromboembolism (VTE) is increased with hormone replacement therapy (HRT); the effect on coronary heart disease (CHD) remains unclear.

Methods and results: RCTs of HRT were identified. Event rates for cerebrovascular disease [stroke, TIA (transient ischaemic attack)], CHD (myocardial infarction, unstable angina, sudden cardiac death), and VTE (pulmonary embolism, deep vein thrombosis) were analysed. Sensitivity analyses were performed by type of HRT (mono vs. dual) and subject age. 31 trials (44 113 subjects) were identified. HRT was associated with increases in stroke (odds ratio, OR, 1.32, 95% confidence intervals, CI, 1.14–1.53) and VTE (OR 2.05, 95% CI 1.44–2.92). In contrast, CHD events were not increased (OR 1.02, 95% CI 0.90–1.11). Ordinal analyses confirmed that stroke severity was increased with HRT (OR 1.31, 95% CI 1.12–1.54). Although most trials included older subjects, age did not significantly affect risk. The addition of progesterone to oestrogen doubled the risk of VTE.

Conclusion: HRT is associated with an increased risk of stroke, stroke severity, and VTE, but not of CHD events. Although most trials studied older patients, increased risk was not related to age. Combined HRT increases the risk of VTE compared with oestrogen monotherapy.

Key Words: Hormone replacement therapy • Myocardial infarction • Randomized controlled trial • Stroke • Venous thromboembolism


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