Warfarin use and prostate cancer risk in the Finnish Randomized Study of Screening for Prostate Cancer

Abstract

Objective: Anticoagulants, especially vitamin K antagonists (VKAs) such as warfarin, have been hypothesized to have antitumor properties, and use of VKAs has been associated with a lower prostate cancer (PCa) risk. This study estimated PCa risk among users of warfarin and other anticoagulants.

Materials and methods: All anticoagulant use among 78,615 men during 1995–2009 was analyzed. Cox regression, adjusted for age, screening trial arm and use of other medications, with medication use as a time-dependent variable, was used to estimate PCa risk overall, and by tumor grade and stage.

Results: In total, 6537 men were diagnosed with PCa during 1995–2009 (1210 among warfarin users). Compared to non-users, warfarin use was associated with an increased risk of PCa [multivariable-adjusted hazard ratio (HR) = 1.11, 95% confidence interval (CI) 1.01–1.22]. This was limited to short-term, low-dose use, and was not observed in long-term use. A similar overall risk increase was observed for Gleason grade 7–10 PCa. Low-dose, short-term use of warfarin was associated with an increased risk of metastatic PCa. However, the increase in risk vanished with continued use. Compared to other anticoagulants, low-dose use of warfarin was associated with a slightly elevated overall PCa risk (HR = 1.19, 95% CI 1.00–1.43). The increase in risk disappeared in long-term, high-dose use.

Conclusions: This study, which included a larger number of PCa cases with warfarin exposure than previous studies, does not support previous notions of decreased risk of PCa among warfarin users. A similar risk of PCa was found among warfarin users and the general population, and no difference in risk was found between warfarin and other anticoagulants.

Keywords:

• Anticoagulant drugs
• cohort
• metastasis
• prostate cancer
• risk
• warfarin

Disclosure statement

We declare the following conflicts of interest: P. T. T. Kinnunen: none; T. J. Murtola: paid consultant for Astellas and Janssen-Cilag, lecture fees from Janssen-Cilag, Abbvie and MSD; K. Talala: none; K. Taari: consulting fee from Abbvie, lecture fee from GlaxoSmithKline, research funding from Medivation, travel support from Astellas and Orion; T. L. J. Tammela: paid consultant for Astellas, GlaxoSmithKline, Pfizer, Orion Pharma and Amgen; A. Auvinen: lecture fee from MSD, paid consultant for Epid Research Inc.