Despite previous studies suggesting the contrary, statins (cholesterol-lowering drugs) may not prevent blood clots (venous thrombo-embolism) in adults, according to a large analysis by international researchers published in this week's PLOS Medicine.
In 2009, an additional analysis of data from a randomized controlled trial called the JUPITER trial reported that the statin rosuvastatin halved the risk of venous thromboembolic events among apparently healthy adults. However, this finding was based on a small number of patients who had thromboembolic events (34 vs 60). To gather more evidence about the possible benefits of statins, a group of international researchers led by Kazem Rahimi from the George Centre for Healthcare Innovation at the University of Oxford in the UK, combined the results (performed a meta-analysis) of 29 suitable published and unpublished randomised controlled trials of the effects of statins involving over 100 000 participants and more than 1000 events: Only two studies presented venous thrombotic events in the published report, but such events had been recorded as adverse events in all of the included trials, which the authors were able to include in their analysis.
In the combined analysis, the authors found that venous thrombosis occurred in 0.9% of people taking statins compared to 1% of people not taking statins, which suggests that statins have a very small, if any, effect. These results did not change when the authors excluded the findings of the JUPITER trial. The authors also found that there was no effect at all in people taking high doses and low doses of statins.
The authors conclude: "this study provides a more detailed assessment of the potential effects of statins (or higher dose statins) on venous thromboembolic events than has previously been possible. We were unable to confirm the large proportional reduction in risk suggested by some previous studies."
The authors add: "However, a more modest but perhaps clinically worthwhile reduction in venous thromboembolic events in some or all types of patient cannot be ruled out."
In an accompanying Perspective article, Frits Rosendaal from the Leiden University Medical Center in The Netherlands (uninvolved in the study) argues that even if the study cannot provide definite answers to the statin question, some tentative conclusions can be drawn. He says: "Firstly, that for the association between statins and venous thrombosis the methodologically strongest analysis shows at most a very small effect. Secondly, if we do not wish to discard the possibility of a beneficial effect for the whole class, any such effects are limited to rosuvastatin."
Funding: This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors. No funding bodies played any role in the design, data collection and analysis, writing or decision to publish this manuscript. KR is supported by the Oxford Martin School and the Oxford NIHR Biomedical Research Centre. NB is supported by a MRC Health of the Public Research Fellowship.
Competing Interests: NB is a member of the secretariat of the Cholesterol Treatment Trialists' (CTT) Collaboration. VK is a member of the steering committee of the SHARP trial (Study of Heart and Renal Protection), and was involved in the 4D Study (German Diabetes and Dialysis Study) as clinical coordinator. JM is supported by the University of Glasgow. MR is a member of the PLOS Medicine Editorial Board. All other authors have declared that no competing interests exist.
Citation: Rahimi K, Bhala N, Kamphuisen P, Emberson J, Biere-Rafi S, et al. (2012) Effect of Statins on Venous Thromboembolic Events: A Meta-analysis of Published and Unpublished Evidence from Randomised Controlled Trials. PLoS Med 9(9): e1001310. doi:10.1371/journal.pmed.1001310
George Centre for Healthcare Innovation
University of Oxford,
Oxford, United Kingdom
+44 (0)1865 617201
Funding: No specific funding was received for writing this article.
Competing Interests: The author reports no competing interests in relation to statins. The author is named on several patents for prothrombotic gene variants (such as Factor V Leiden) but does not benefit personally from royalties on these.
Citation: Rosendaal FR (2012) Statins and Venous Thrombosis: A Story Too Good to Be True? PLoS Med 9(9): e1001311. doi:10.1371/journal.pmed.1001311
Frits R. Rosendaal
Department of Clinical Epidemiology and Department of Thrombosis and Haemostasis
Leiden University Medical Center
Leiden, The Netherlands
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