Risk of prostate cancer death in long-term users of warfarin: a population-based case–control study
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Recent evidence suggests that warfarin use may be associated with a reduced risk of prostate cancer. We aimed to determine whether exposure to warfarin is also associated with a reduced risk of prostate cancer death.
A nested case–control study was conducted within a population-based cohort of 10,012 men aged ≥50 years with newly diagnosed prostate cancer between 1985 and 2002 and with no history of cancer since 1970 using the linked records of Saskatchewan Health and Saskatchewan Cancer Agency registry. We identified 2,309 cases who died of prostate cancer during follow-up. For each case, one control alive at the time of the case’s death and matched for length of follow-up (±6 months) was randomly selected. Prescription counts were used to define warfarin exposure. Multivariate conditional logistic regression analysis was used to calculate the adjusted incidence rates of prostate cancer death in relation to warfarin use while adjusting for confounding by age, year of prostate cancer diagnosis, clinical stage and grade of cancer at diagnosis, Chronic Disease Score, and use of warfarin before diagnosis.
Ever use of warfarin following a diagnosis of prostate cancer was associated with an adjusted rate ratio of 1.44 (95 % confidence interval (CI) 1.33–1.84) for prostate cancer death. The adjusted rate ratio with one-year use of warfarin was 1.77 (95 % CI 1.25–2.50) compared to never use. The unadjusted rate ratio with five-year use of warfarin was 0.64 (95 % CI 0.40–1.00) and remained unchanged in the adjusted analysis (0.65, 95 % CI 0.37–1.13), although no longer statistically significant.
Our study does not provide conclusive evidence for a protective effect of long-term warfarin on prostate cancer-specific mortality. Moreover, short-term warfarin use may be associated with an increased risk of prostate cancer death.
KeywordsProstate cancer Pharmacoepidemiology Warfarin Mortality
The study is based, in part, on de-identified data provided by the Saskatchewan Ministry of Health. The interpretation and conclusions contained herein do not necessarily represent those of the Government of Saskatchewan or the Saskatchewan Ministry of Health. The study was also based on data provided by the Saskatchewan Cancer Agency, which does not take any responsibility for the analysis of the data or the interpretation of the results. The study was funded by a peer-reviewed grant from the Canadian Institutes of Health Research (Grant #86580). The funding source had no role in the design of the study, the collection and analysis of data, or the interpretation of the results.
Conflict of Interest
The authors declare no conflict of interest.
The study protocol was approved by the Data Use Committee of the Saskatchewan Cancer Agency and the Regina Qu’Appelle Health Region Research Ethics Board. The study protocol was also approved by the Research Ethics Office of the Jewish General Hospital, Montreal, Québec. Because the study used de-identified administrative data maintained by SH and SCA, no individual consent was obtained. SH was responsible for the linkage, preparation, and de-identification of the data sets. Only data relevant to the study were provided for analyses.
- 14.Fritz A, Percy C, Jack A, Shanmugaratnam K, Sobin L, Parkin DM, Whelan S (2000) International classification of diseases for oncology (ICD-0-3), 3rd edn. World Health Organization, GenevaGoogle Scholar
- 15.Stratospheric ozone and human health project. Saskatchewan Cancer Registry. Socioeconomic Data Applications Center’s (SEDAC). http://sedac.ciesin.columbia.edu/ozone/regs/saskatchewan.html. Accessed 14 May 2012
- 23.Chahinian AP, Propert KJ, Ware JH, Zimmer B, Perry MC, Hirsh V, Skarin A, Kopel S, Holland JF, Comis RL, Green MR (1989) A randomized trial of anticoagulation with warfarin and of alternating chemotherapy in extensive small-cell lung cancer by the Cancer and Leukemia Group B. J Clin Oncol 7:993–1002PubMedGoogle Scholar
- 26.Maurer LH, Herndon JE 2nd, Hollis DR, Aisner J, Carey RW, Skarin AT, Perry MC, Eaton WL, Zacharski LL, Hammond S, Green MR (1997) Randomized trial of chemotherapy and radiation therapy with or without warfarin for limited-stage small-cell lung cancer: a cancer and leukemia group B study. J Clin Oncol 15:3378–3387PubMedGoogle Scholar
- 27.Akl EA, Vasireddi SR, Gunukula S, Yosuico VE, Barba M, Terrenato I, Sperati F, Schünemann H (2011) Oral anticoagulation in patients with cancer who have no therapeutic or prophylactic indication for anticoagulation. Cochrane Database Syst Rev 6:CD006466Google Scholar
- 28.Opatrny L, Delaney JA, Tagalakis V, Kahn SR, Suissa S (2007) Warfarin use and the decreased risk of prostate cancer (#PM-529). Poster presentation at the XXIst congress of the international society of thrombosis and haemostasis. GenevaGoogle Scholar
- 30.Agnelli G, Verso M (2011) Management of venous thromboembolism in patients with cancer. J Thromb Haemost 9(Suppl. 1):313–324Google Scholar
- 34.International Statistical Classification of Diseases and Related Health Problems (1992–1994) Tenth revision, vol 1–3. World Health Organization, GenevaGoogle Scholar
- 36.Statistics Canada (2005) Comparability of ICD-10 and ICD-9 for mortality statistics in Canada. Ministry responsible for Statistics Canada, Ottawa, pp 5–7Google Scholar
- 37.Rothwell PM, Price JF, Fowkes FG, Zanchetti A, Roncaglioni MC, Tognoni G, Lee R, Belch JF, Wilson M, Mehta Z, Meade TW (2012) Short-term effects of daily aspirin on cancer incidence, mortality, and non-vascular death: analysis of the time course of risks and benefits in 51 randomized controlled trials. Lancet 379:1602–1612PubMedCrossRefGoogle Scholar