Use of Warfarin or Direct Oral Anticoagulants and Risk of Prostate Cancer in PCBaSe: A Nationwide Case-Control Study.

Jonathan Parker,Kerri Beckmann,Johan Styrke,Mieke Van Hemelrijck,Jan Adolfsson,Bertil Lindahl,Danielle Crawley,Mats Lambe,Hans Garmo,Pär Stattin

doi:10.3389/fonc.2020.571838

Abstract

Existing literature examining warfarin's association with prostate cancer (PCa) risk provides conflicting results, while the association with direct oral anticoagulants (DOACs) has not yet been studied. We investigated the association of warfarin and DOAC use on PCa risk among men within the population-based Prostate Cancer database Sweden (PCBaSe), using a case-control design. The study population included PCa cases diagnosed 2014–2016 and five age-matched PCa-free controls. Conditional logistic regression was used to estimate odds ratios (ORs) with 95% confidence intervals (CI) for PCa associated with warfarin and DOAC use, adjusted for marital status, education level, other drug use, and comorbidities. Among 31,591 cases and 156,802 controls, there were 18,522 (9.8%) warfarin and 4,455 (2.4%) DOAC users. Warfarin ever-use was associated with reduced risk of PCa overall (OR 0.92 95% CI 0.88–0.96) as were both past and current use. DOAC use was not associated with PCa risk. For some warfarin exposures, decreased risk was observed for unfavorable PCa (high risk/locally advanced/distant metastatic) but not with favorable PCa (low/intermediate risk). Increased risk of favorable PCa was observed for men whose initial warfarin exposure occurred in the 12 month period before diagnosis (OR 1.39; 95% CI 1.13–1.70). Our findings are consistent with previous publications reporting decreased PCa risk with warfarin exposure. Increased risk of favorable PCa suggests detection bias due to increased prostate specific antigen testing when starting on warfarin. Decreased overall PCa risk could reflect bias due to reduced biopsy rates among long-term warfarin users.

Highlights

Prostate cancer (PCa) is the second most common cancer in men with an estimated 1.3 million incident cases diagnosed in 2018 [1]
We used data from Prostate Cancer database Sweden (PCBaSe) 4.0, which includes all men recorded in the National Prostate Cancer Register (NPCR) of Sweden diagnosed with PCa since 1998
The association between warfarin use and overall PCa risk varied depending on the timing of initial exposure, with risk being significantly lower when first exposure was more than 12 months prior to PCa diagnosis, but non-significantly increased when first exposure was within 12 months of diagnosis

Summary

Introduction

Prostate cancer (PCa) is the second most common cancer in men with an estimated 1.3 million incident cases diagnosed in 2018 [1]. Established risk factors for PCa include age, ethnicity, and family history [2] Anticoagulants such as vitamin K antagonists (VKAs) are commonly prescribed to patients at risk of, or with a history of, thromboembolic events, atrial fibrillation/flutter and mechanical heart valve [3]. Many of these men will be diagnosed with PCa. A possible protective effect of VKAs on the development of PCa was first reported in 2000 [4] prompting an interest in the possible anti-PCa effect of VKAs, in particular, warfarin [5,6,7,8,9,10,11,12]. Detection bias due to reluctance to perform prostate biopsies among men on chronic oral anticoagulation therapy has been suggested as a possible explanation for decreased risk of Pca in men on warfarin [13]

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