Patients with cancer are more likely than those without cancer to develop a blood clot (thrombosis) in the blood vessels that return the blood to the heart (veins) and in the blood vessels of the lungs. These blood clots in veins are known as deep vein thrombosis (DVT) and in the blood vessels of the lungs known as pulmonary embolism (PE). Clots in the veins and the lungs need blood thinners (anticoagulants) to treat them. When clots occur, cancer patients carry a higher risk of recurring clots on and off treatment and they are also more likely to bleed on blood thinning treatments. Therefore, it is critical to use blood thinners that optimize the safety and benefits when treating cancer-associated blood clots.
There are two main types of blood thinners that are recommended to treat these clots. The tablets which are direct-acting oral blood thinners (DOACs) and the injections (low molecular-weight heparin (LMWH)). The studies or trials of these drugs show the tablet may reduce clot risk but may potentially lead to more frequent bleeding, particularly in those with certain risk factors such as kidney disease, stomach ulcers, previous bleeding problems and specific cancers, such as stomach and bladder cancer.
We seek to examine the effectiveness and safety of the tablets versus the injections for treatment of clots in cancer patients. This will help medical practitioners to better understand these treatments and therefore provide them appropriately.
This observational cohort study aims to investigate the effectiveness and safety of direct oral anticoagulant (DOAC) and low molecular weight heparin (LMWH) use in patients with active cancer-associated venous thromboembolism (CAT).
A cohort of patients with venous thromboembolisms (VTEs), defined as deep vein thrombosis or pulmonary embolism, after 01/01/2013, a cancer recording within 180 days before the VTE and recorded DOAC or LMWH use within 30 days after the CAT will be defined. Propensity scores for DOAC initiation in CAT will be estimated from multivariate logistic regression models in the complete study cohort. For each cohort member with DOAC treatment, up to 5 CAT patients with LMWH treatment will be matched based on propensity scores and the calendar day of cohort entry ±180 days.
Exposures of interest are DOAC compared with LMWH, and rivaroxaban compared with LMWH use. The outcomes of interest are VTE recurrences, significant bleeding (major bleeding and clinically-relevant non-major bleeding requiring hospitalization) and all-cause mortality at 3, 6 and 12 months following CAT.
Sub-distribution hazard ratios (SHRs) for VTE recurrence and significant bleeding will be estimated from multivariate Fine and Gray regression models accounting for the competing risk of mortality and adjusting for anticoagulant type (i.e. DOAC or LMWH), propensity score and potential confounders in the first 3, 6 and 12 months following the initial CAT respectively. For all-cause mortality hazard ratios (HRs) from Cox regression models will be used.
VTE recurrences; significant bleeding events including major bleeds and clinically relevant non-major bleeds requiring hospitalisation; all-cause mortality.
Marcela Rivera - Chief Investigator - Bayer AG
Carlos Martinez - Corresponding Applicant - Institute for Epidemiology, Statistics and Informatics GmbH (Pharma Epi)
Alexander Cohen - Collaborator - King's College London (KCL)
Christopher Wallenhorst - Collaborator - Institute for Epidemiology, Statistics and Informatics GmbH (Pharma Epi)
George Psaroudakis - Collaborator - Bayer AG
Gunnar Brobert - Collaborator - Bayer AG
Khaled Abdelgawwad - Collaborator - Bayer AG
Samuel Fatoba - Collaborator - Bayer AG
Stephan Rietbrock - Collaborator - Institute for Epidemiology, Statistics and Informatics GmbH (Pharma Epi)
HES Admitted Patient Care;HES Outpatient;ONS Death Registration Data;Patient Level Index of Multiple Deprivation