Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Meta-Analysis
. 2022 Feb 21;118(3):897-903.
doi: 10.1093/cvr/cvab078.

Rosuvastatin for the prevention of venous thromboembolism: a pooled analysis of the HOPE-3 and JUPITER randomized controlled trials

Philip Joseph  1 , Robert Glynn  2 , Eva Lonn  1 , Chinthanie Ramasundarahettige  1 , John Eikelboom  1 , Jean MacFadyen  2 , Paul Ridker  2 , Salim Yusuf  1
Affiliations
Meta-Analysis

Rosuvastatin for the prevention of venous thromboembolism: a pooled analysis of the HOPE-3 and JUPITER randomized controlled trials

Philip Joseph et al. Cardiovasc Res. .

Abstract

Aims: To examine the association between rosuvastatin and VTE risk, and whether effects vary in different subpopulations stratified by key demographic, cardiovascular disease (CVD) risk factors, and other risk factors associated with VTE.

Methods and results: An individual participant data meta-analysis was conducted across two randomized controlled trials in 30 507 participants over a mean follow-up of 3.62 years, individuals had no prior history of vascular disease but were at intermediate CV risk. In both trials, participants were randomized to receive rosuvastatin or matching placebo. The primary outcome was VTE during follow-up, defined as either deep vein thrombosis or pulmonary embolism. Associations between rosuvastatin and VTE were examined in the overall pooled cohort, and subpopulations stratified by demographic risk factors (i.e. age and sex), CVD risk factors (i.e. obesity, smoking, lipid levels, blood pressure levels, and C-reactive protein level), and a history of cancer. Mean age was 65.96 (SD 7.19) years of age, and 17 832 (58.45%) were male and 5434 (17.82%) were smokers, median BMI was 27.6 [interquartile range (IQR) 24.7-31.1] kg/m2, and median CRP level was 3.4 (IQR 2.1-6.0) mg/L. There were 139 VTE events. In the pooled cohort, rosuvastatin was associated with a large proportional reduction in the risk of VTE (hazard ratio 0.53, 95% CI 0.37-0.75). No significant interactions were observed between treatment with rosuvastatin and the risk of VTE across subpopulations stratified by demographic, CVD risk factors, or a history of cancer (P-values for interactions >0.05 for all subgroups).

Conclusion: Rosuvastatin is associated with a 47% proportional reduction in the risk of VTE, and its effect is consistent both in the presence or absence of VTE-related clinical risk factors.

Keywords: Statin; Venous thromboembolism.

PubMed Disclaimer

Figures

None
Graphical abstract
Figure 1
Figure 1
(A and B) Risk of VTE associated with rosuvastatin in pooled analysis. (A) Forest plot and (B) Kaplan–Meyer survival curves for VTE are presented for the comparison of rosuvastatin vs. placebo across both randomized controlled trials. The HOPE-3 follow-up period was longer than in JUPITER, and Kaplan–Meyer curves were truncated to 5 years since beyond this time, effects would almost exclusively be related to the HOPE-3 study population. Analysis (N=30 507 participants) was performed using Cox frailty model. 95% CI, 95% confidence interval; HR, hazard ratio.
Figure 2
Figure 2
Effect of rosuvastatin on VTE risk by subgroups. *The higher proportion of participants receiving anti-platelet therapy having VTE events may be due to confounding conditions for which anti-platelet therapy was indicated. Analysis (N=30 507 participants) was performed using Cox frailty model. BP, blood pressure; CRP, C-reactive protein; 95% CI, 95% confidence interval; HDL, high-density lipoprotein; HR, hazard ratio; LDL, low-density lipoprotein.
See this image and copyright information in PMC

References

    1. Folsom AR, Lutsey PL, Astor BC, Cushman M.. C-reactive protein and venous thromboembolism. A prospective investigation in the ARIC cohort. Thromb Haemost 2009;102:615–619. - PMC - PubMed
    1. Fox EA, Kahn SR.. The relationship between inflammation and venous thrombosis. A systematic review of clinical studies. Thromb Haemost 2005;94:362–365. - PubMed
    1. Gregson J, Kaptoge S, Bolton T, Pennells L, Willeit P, Burgess S, Bell S, Sweeting M, Rimm EB, Kabrhel C, Zöller B, Assmann G, Gudnason V, Folsom AR, Arndt V, Fletcher A, Norman PE, Nordestgaard BG, Kitamura A, Mahmoodi BK, Whincup PH, Knuiman M, Salomaa V, Meisinger C, Koenig W, Kavousi M, Völzke H, Cooper JA, Ninomiya T, Casiglia E, Rodriguez B, Ben-Shlomo Y, Després J-P, Simons L, Barrett-Connor E, Björkelund C, Notdurfter M, Kromhout D, Price J, Sutherland SE, Sundström J, Kauhanen J, Gallacher J, Beulens JWJ, Dankner R, Cooper C, Giampaoli S, Deen JF, Gómez de la Cámara A, Kuller LH, Rosengren A, Svensson PJ, Nagel D, Crespo CJ, Brenner H, Albertorio-Diaz JR, Atkins R, Brunner EJ, Shipley M, Njølstad I, Lawlor DA, van der Schouw YT, Selmer RM, Trevisan M, Verschuren WMM, Greenland P, Wassertheil-Smoller S, Lowe GDO, Wood AM, Butterworth AS, Thompson SG, Danesh J, Di Angelantonio E, Meade T; Emerging Risk Factors Collaboration. Cardiovascular risk factors associated with venous thromboembolism. JAMA Cardiol 2019;4:163–173. - PMC - PubMed
    1. Roach REJ, Venemans A, Cannegieter SC, Lijfering WM.. Differential risks in men and women for first and recurrent venous thrombosis: the role of genes and environment: reply. J Thromb Haemost 2015;13:886–887. - PubMed
    1. Kunutsor SK, Seidu S, Khunti K.. Statins and primary prevention of venous thromboembolism: a systematic review and meta-analysis. Lancet Haematol 2017;4:e83–e93. - PubMed

Publication types

MeSH terms

Substances