The effect of warfarin therapy on breast, colorectal, lung, and prostate cancer survival: a population-based cohort study using the Clinical Practice Research Datalink

O’Rorke, Michael; Murray, Liam; Hughes, Carmel; Cantwell, Marie; Cardwell, Christopher

doi:10.1007/s10552-014-0511-2

Cited by 16 publications

(10 citation statements)

References 41 publications

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“…The role of anti-coagulants such as warfarin and LMWH in prostate cancer remain controversial in the literature. Our study found a detrimental effect of warfarin however other retrospective reviews have found inconclusive or no effects of warfarin [ 29 – 31 ]. However, a recent single institution retrospective series of LMWH treated men (for deep venous thrombosis only) with docetaxel (17/247) suggested benefit on multi-variate analysis (HR, 0.48; P = .035) [ 19 ].…”

Section: Discussioncontrasting

confidence: 74%

Assessment of a prognostic model, PSA metrics and toxicities in metastatic castrate resistant prostate cancer using data from Project Data Sphere (PDS)

et al. 2017

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BackgroundPrognostic models in metastatic castrate resistant prostate cancer (mCRPC) may have clinical utility. Using data from PDS, we aimed to 1) validate a contemporary prognostic model (Templeton et al., 2014) 2) evaluate prognostic impact of concomitant medications and PSA decrease 3) evaluate factors associated with docetaxel toxicity.MethodsWe accessed data on 2,449 mCRPC patients in PDS. The existing model was validated with a continuous risk score, time-dependent receiver operating characteristic (ROC) curves, and corresponding time-dependent Area under the Curve (tAUC). The prognostic effects of concomitant medications and PSA response were assessed by Cox proportional hazards models. One year tAUC was calculated for multivariable prognostic model optimized to our data. Conditional logistic regression models were used to assess associations with grade 3/4 adverse events (G3/4 AE) at baseline and after cycle 1 of treatment.ResultsDespite limitations of the PDS data set, the existing model was validated; one year AUC, was 0.68 (95% CI 95% CI, .66 to .71) to 0.78 (95%CI, .74 to .81) depending on the subset of datasets used. A new model was constructed with an AUC of .74 (.72 to .77). Concomitant medications low molecular weight heparin and warfarin were associated with poorer survival, Metformin and Cox2 inhibitors were associated with better outcome. PSA response was associated with survival, the effect of which was greatest early in follow-up. Age was associated with baseline risk of G3/4 AE. The odds of experiencing G3/4 AE later on in treatment were significantly greater for subjects who experienced a G3/4 AE in their first cycle (OR 3.53, 95% CI 2.53–4.91, p < .0001).ConclusionDespite heterogeneous data collection protocols, PDS provides access to large datasets for novel outcomes analysis. In this paper, we demonstrate its utility for validating existing models and novel model generation including the utility of concomitant medications in outcome analyses, as well as the effect of PSA response on survival and toxicity prediction.

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Section: Discussioncontrasting

confidence: 74%

Assessment of a prognostic model, PSA metrics and toxicities in metastatic castrate resistant prostate cancer using data from Project Data Sphere (PDS)

et al. 2017

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“…In a cohort study including 12,186 men with PCa, but no information on stage no evidence was found for an association between PCa death and pre-diagnostic use of warfarin during a mean follow-up of 3.7 years [12]. In a sensitivity analysis post-diagnostic use was associated with an increased risk of PCa death.…”

Section: Discussionmentioning

confidence: 99%

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

et al. 2017

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BackgroundVenous 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.MethodsThe 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.ResultsIn 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.ConclusionsWe 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.Electronic supplementary materialThe online version of this article (10.1186/s12885-017-3579-8) contains supplementary material, which is available to authorized users.

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“…Few observational studies examine the association between breast cancer mortality and anticoagulant use. To the authors' knowledge, only one previous study has been published on this topic, and it was limited to warfarin use [18]. That study found no risk association for pre-diagnostic warfarin use, but an increased risk of breast cancer death was associated with post-diagnostic warfarin use in subjects who had not previously received the drug (HR 1.36, 95% CI 1.12-1.64).…”

Section: Introductionmentioning

confidence: 91%

Anticoagulants and Breast Cancer Survival: A Nationwide Cohort Study

Kinnunen

Murto

Artama

et al. 2020

Cancer Epidemiology, Biomarkers &Amp; Prevention

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The effect of warfarin therapy on breast, colorectal, lung, and prostate cancer survival: a population-based cohort study using the Clinical Practice Research Datalink

Abstract: There was little evidence of associations between pre-diagnostic use of warfarin and cancer-specific mortality in lung, prostate, breast, or colorectal cancer patients.

Cited by 16 publications

References 41 publications

Assessment of a prognostic model, PSA metrics and toxicities in metastatic castrate resistant prostate cancer using data from Project Data Sphere (PDS)

Assessment of a prognostic model, PSA metrics and toxicities in metastatic castrate resistant prostate cancer using data from Project Data Sphere (PDS)

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

Anticoagulants and Breast Cancer Survival: A Nationwide Cohort Study

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