Anticoagulants and Breast Cancer Survival: A Nationwide Cohort Study.

BACKGROUND: Various components of the coagulation cascade have been linked to breast cancer progression. In vivo results suggest that anticoagulants possess anticancer properties, but there are virtually no studies in human populations. Our nationwide study explored the association between anticoagulant use and breast cancer survival. METHODS: All anticoagulants used from 1995 to 2015 in women (n = 73,170) diagnosed with invasive breast cancer in Finland between 1995 and 2013 were identified from the national prescription database; women were identified from the Finnish Cancer Registry. Cox regressions were performed to analyze breast cancer survival as a function of pre- and postdiagnostic anticoagulant use; analyses were conducted for different anticoagulant subtypes and overall. Models were adjusted for age, mammography screening, tumor clinical characteristics, comorbidities, statin use, antidiabetic use, and antihypertensive use. To control for immortal time bias, postdiagnostic anticoagulant use was analyzed as a time-dependent variable. RESULTS: At a median of 5.8 years after breast cancer diagnosis, 10,900 (15%) women had died from breast cancer. In total, 25,622 (35%) women had used anticoagulants during the study period. Postdiagnostic anticoagulant use increased the risk of breast cancer death (HR = 1.41; 95% confidence interval, 1.33-1.49). The risk was especially high for low-molecular weight heparin, although the effect disappeared in long-term users. CONCLUSIONS: Anticoagulant use provides no clinical benefit for breast cancer survival; however, the association between thrombosis and cancer might mask potential survival benefits. IMPACT: Future pharmacoepidemiologic studies should adjust for anticoagulant use. Research should focus on the use of new oral anticoagulants because these are rarely studied and might be associated with improved breast cancer survival.

Prostate cancer-specific survival among warfarin users in the Finnish Randomized Study of Screening for Prostate Cancer.

BACKGROUND: Venous thromboembolic events (VTE) are common in cancer patients and associated with higher mortality. In vivo thrombosis and anticoagulation might be involved in tumor growth and progression. We studied the association of warfarin and other anticoagulant use as antithrombotic medication and prostate cancer (PCa) death in men with the disease. METHODS: The study included 6,537 men diagnosed with PCa during 1995-2009. Information on anticoagulant use was obtained from a national reimbursement registry. Cox regression with adjustment for age, PCa risk group, primary therapy and use of other medication was performed to compare risk of PCa death between warfarin users with 1) men using other types of anticoagulants and 2) non-users of anticoagulants. Medication use was analyzed as a time-dependent variable to minimize immortal time bias. RESULTS: In total, 728 men died from PCa during a median follow-up of 9 years. Compared to anticoagulant non-users, post-diagnostic use of warfarin was associated with an increased risk of PCa death (overall HR 1.47, 95% CI 1.13-1.93). However, this was limited to low-dose, low-intensity use. Otherwise, the risk was similar to anticoagulant non-users. Additionally, we found no risk difference between warfarin and other types of anticoagulants. Pre-diagnostic use of warfarin was not associated with the risk of PCa death. CONCLUSIONS: We found no reduction in risk of PCa death associated with warfarin use. Conversely, the risk was increased in short-term use, which is probably explained by a higher risk of thrombotic events prompting warfarin use in patients with terminal PCa.

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

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.