Abstract
PurposeAnticoagulants may reduce mortality of cancer patients, though the evidence remains controversial. We studied the association between different anticoagulants and cancer death.MethodsAll anticoagulant use during 1995–2015 was analyzed among 75,336 men in the Finnish Randomized Study of Screening for Prostate Cancer. Men with prevalent cancer were excluded. Multivariable Cox regression was performed to compare risk of death from any cancer and disease-specific death from 9 specific cancer types between (1) anticoagulant users overall and (2) warfarin users compared to anticoagulant non-users and (3) warfarin or (4) low-molecular-weight heparins (LMWH) compared to users of other anticoagulants. Medication use was analyzed as time-dependent variable to minimize immortal time bias. 1-, 2- and 3-year lag-time analyses were performed.ResultsDuring a median follow-up of 17.2 years, a total of 27,233 men died of whom 8033 with cancer as the primary cause of death. In total, 32,628 men (43%) used anticoagulants. Any anticoagulant use was associated with an increased risk of cancer death (HR = 2.50, 95% CI 2.37–2.64) compared to non-users. Risk was similar independent of the amount, duration, or intensity of use. The risk increase was observed both among warfarin and LMWH users, although not as strong in warfarin users. Additionally, cancer-specific risks of death were similar to overall cancer mortality in all anticoagulant categories.ConclusionOur study does not support reduced cancer mortality among anticoagulant users. Future studies on drug use and cancer mortality should be adjusted for anticoagulants as they are associated with significantly higher risk of cancer death.
Highlights
Venous thromboembolism (VTE) is a clinically important complication among patients with malignancies, as the risk of VTE is five- to sevenfold in patients with cancer [1, 2]
Risk of cancer death in relation to warfarin use Compared to other anticoagulants, use of warfarin was associated with a significantly lower risk of cancer death (HR = 0.45, 95% confidence intervals (CIs) 0.41–0.50)
This was observed regardless of the amount, duration, or intensity of use (Table 2), the risk decrease being most apparent in high-dose and high-intensity use of warfarin
Summary
Venous thromboembolism (VTE) is a clinically important complication among patients with malignancies, as the risk of VTE is five- to sevenfold in patients with cancer [1, 2]. Cancer patients with deep VTE or pulmonary embolism have an eightfold risk of death compared to VTE in patients without cancer [4]. Prognosis for cancers patients with embolism is fairly poor: 1-year overall survival is only 38% [5]. It has been reported that tissue factor pathway inhibition has been reported to be relevant in formation of certain brain tumors [6]. It has further been suggested that cancer cells may activate coagulation through increased expression of tissue factor increasing malignant phenotype of cancer cells [7]
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