Association of statins, aspirin, and venous thromboembolism in women with endometrial cancer

Koji Matsuo; Marianne S Hom; Akira Yabuno; Masako Shida; Mamoru Kakuda; Sosuke Adachi; Rachel S Mandelbaum; Yutaka Ueda; Kosei Hasegawa; Takayuki Enomoto; Mikio Mikami; Lynda D Roman

doi:10.1016/j.ygyno.2018.12.020

Association of statins, aspirin, and venous thromboembolism in women with endometrial cancer

Gynecol Oncol. 2019 Mar;152(3):605-611. doi: 10.1016/j.ygyno.2018.12.020. Epub 2019 Jan 5.

Authors

Affiliations

¹ Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, University of Southern California, Los Angeles, CA, USA; Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, CA, USA. Electronic address: koji.matsuo@med.usc.edu.
² Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, University of Southern California, Los Angeles, CA, USA.
³ Department of Gynecologic Oncology, Saitama Medical University International Medical Center, Saitama, Japan.
⁴ Department of Obstetrics and Gynecology, Tokai University School of Medicine, Kanagawa, Japan.
⁵ Department of Obstetrics and Gynecology, Osaka University Graduate School of Medicine, Osaka, Japan.
⁶ Department of Obstetrics and Gynecology, Niigata University School of Medicine, Osaka, Japan.
⁷ Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, University of Southern California, Los Angeles, CA, USA; Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, CA, USA.

Abstract

Objective: The anti-thrombogenic effects of statins and aspirin have been reported in various malignancies but have not been well examined in endometrial cancer. This study examined the association between statin and/or aspirin use and venous thromboembolism (VTE) risk in endometrial cancer.

Methods: This is a multi-center retrospective study examining 2527 women with endometrial cancer between 2000 and 2015. Statin and aspirin use at diagnosis was correlated to VTE risk during follow-up on multivariable analysis.

Results: There were 132 VTE events with a 5-year cumulative incidence rate of 6.1%. There were 392 (15.5%) statin users and 219 (8.7%) aspirin users, respectively. On multivariable analysis, statin use was associated with an approximately 60% decreased risk of VTE when compared to non-users (5-year cumulative rates 2.5% versus 6.7%, adjusted-hazard ratio [HR] 0.42, 95% confidence interval [CI] 0.19-0.92, P = 0.030) whereas aspirin did not demonstrate statistical significance (2.0% versus 6.5%, adjusted-HR 0.54, 95%CI 0.19-1.51, P = 0.24). There was a trend of joint effect between statin and aspirin although it did not demonstrate statistical significance: VTE risks for dual statin/aspirin user (adjusted-HR 0.27, 95%CI 0.04-2.07), statin alone (adjusted-HR 0.40, 95%CI 0.18-0.93), and aspirin alone (adjusted-HR 0.51, 95%CI 0.16-1.64) compared to non-use after adjusting for patient characteristics, tumor factors, treatment types, and survival events (P-interaction = 0.090). When stratified by statin type, simvastatin demonstrated the largest reduction of VTE risk (5-year cumulative rates 1.1% versus 6.7%, adjusted-HR 0.17, 95%CI 0.02-1.30, P = 0.088). Obesity, absence of diabetes mellitus, type II histology, and recurrent disease were the factors associated with decreased VTE risk with statin use (all, P-interaction<0.05).

Conclusion: Our study suggests that statin use may be associated with decreased risk of VTE in women with endometrial cancer.

Keywords: Aspirin; Endometrial neoplasms; Hydroxymethylglutaryl-CoA reductase Inhibitors; Incidence; Venous thromboembolism.

Publication types

Multicenter Study
Research Support, Non-U.S. Gov't

MeSH terms

Aspirin / administration & dosage*
Endometrial Neoplasms / epidemiology*
Female
Humans
Hydroxymethylglutaryl-CoA Reductase Inhibitors / administration & dosage*
Incidence
Retrospective Studies
Venous Thromboembolism / epidemiology*

Substances

Hydroxymethylglutaryl-CoA Reductase Inhibitors
Aspirin

Grants and funding

P30 CA014089/CA/NCI NIH HHS/United States