Use of vitamin K antagonists and risk of prostate cancer: Meta–analysis and nationwide case–control study

Abstract

Use of vitamin K antagonists (VKAs) has been suggested to reduce the risk of prostate cancer. We conducted a nested case–control study using Danish demographic and health data registries and summarized existing evidence in a meta‐analysis. The case–control study included all Danish men aged 40–85 years with incident histologically verified prostate adenocarcinoma between 2005 and 2015 (cases). For each case, we selected 10 age–matched controls. We used conditional logistic regression to estimate odds ratios (ORs) with 95% confidence intervals (CI) for prostate cancer associated with long–term VKA use adjusted for concomitant drug use, medical history and socioeconomic status. Among 38,832 prostate cancer cases, 1,089 (2.8%) had used VKAs for 3 or more years compared to 10,803 (2.8%) controls yielding a crude OR of 1.01 (95% CI, 0.95–1.08). Multivariable adjustment for covariates had limited influence on the association (OR, 1.03; 95% CI, 0.97–1.10). We observed no dose–response relationship (e.g. OR for 5–10 years of use, 1.06 95% CI, 0.97–1.16). We included 8 studies in the meta–analysis reporting effect estimates from 0.51 (95% CI, 0.23–1.13) to 1.10 (95% CI, 0.94–1.40). Using random effect methods, a pooled effect estimate of 0.86 (95% CI, 0.70–1.05) was obtained; however, there was considerable across–study heterogeneity (I2: 93.9%). In conclusion, we did not observe a reduced risk of prostate cancer associated with VKA use in this nationwide study and, taken together with previous study findings, a major protective effect of VKAs against prostate cancer seems unlikely.

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

“…Similarly, Haaland et al ( 7 ) found a decreased PCa incidence among both warfarin users, and men with atrial fibrillation. However, not all studies have reported a decreased risk among long-term VKA users ( 5 , 6 , 8 , 9 ). Blanc-Lapierre et al ( 6 ) found a weak non-significant negative association for oral anticoagulant use and risk of PCa, while Ahern et al ( 5 ) found no evidence of an association for VKA use.…”

“…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 – 12 ). However, to date evidence is conflicting, with a recent meta-analysis finding no association between VKAs and PCa risk ( 9 ). 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 ).…”

Chronic oral anticoagluation and risk of prostate cancer: Evidence of detection bias

“…In this national population-based study, men who were treated with chronic anticoagulation for prosthetic heart valve thromboprophylaxis had lower risks of prostate cancer than men in the general population, consistent with several prior studies. 9 However, this association was greatest among men observed from 2000 to 2001, and decreased over time so that no significant difference in risk of prostate cancer was present among men who enrolled in 2008-2010 and followed to 2015. The attenuation of the protective association in the anticoagulation group corresponded with decreased use of prostate biopsies in the general population group.…”

“…Men treated with warfarin have been reported to have lower risks of prostate cancer than men not treated with warfarin in several studies . A recent meta‐analysis of eight studies indicated that the risk was ~15% lower among men treated with warfarin, although with heterogeneity among estimates.…”

“…Men treated with warfarin have been reported to have lower risks of prostate cancer than men not treated with warfarin in several studies. [1][2][3][4][5][6][7][8][9] A recent meta-analysis of eight studies indicated that the risk was~15% lower among men treated with warfarin, although with heterogeneity among estimates. Among studies that examined the association of warfarin treatment with a range of site-specific cancers, the protection was somewhat specific for prostate cancer, although the biological mechanisms that possibly account for this association are unclear.…”