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

Int J Cancer. 2019 Apr 1;144(7):1522-1529. doi: 10.1002/ijc.31886. Epub 2018 Nov 13.


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.

Keywords: anticoagulant drugs; case-control studies; prostate cancer; risk factors; warfarin.

Publication types

  • Meta-Analysis
  • Systematic Review

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Case-Control Studies
  • Denmark / epidemiology
  • Humans
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / administration & dosage
  • Logistic Models
  • Male
  • Middle Aged
  • Odds Ratio
  • Phenprocoumon / administration & dosage
  • Prostatic Neoplasms / epidemiology*
  • Prostatic Neoplasms / prevention & control
  • Registries
  • Vitamin K / antagonists & inhibitors*
  • Warfarin / administration & dosage


  • Hydroxymethylglutaryl-CoA Reductase Inhibitors
  • Vitamin K
  • Warfarin
  • Phenprocoumon