Physicians' Academy for Cardiovascular Education

Similar bleeding with DOAC as with LMWH in those with cancer-associated thrombosis

Bleeding with Apixaban and Dalteparin in Patients with Cancer-Associated Venous Thromboembolism: Results from the Caravaggio Study.

Literature - Ageno W, Vedovati MC, Cohen A, et al. - Thromb Haemost. 2020 Nov 17. doi: 10.1055/s-0040-1720975.

Introduction and methods

Direct oral anticoagulants (DOACs) have a similar efficacy profile compared to subcutaneous injected low-molecular-weight-heparin (LMWH) in patients treated for cancer-associated thrombosis (CAT) [1]. However, safety concerns were raised by clinical trials that reported increased rates of major bleeding events, mostly occurring at the gastrointestinal tract, in patients with CAT using the DOAC edoxaban or rivaroxaban [2,3]. Recent guidelines have favored the use of DOACs in patients with CAT, but have advised caution or exclusion in patients with gastrointestinal cancer [1, 4-7].

This subanalysis of the Caravaggio study compared the sites of major and clinically relevant non-major bleeding (CRNMB) events, associated cancer sites, clinical presentation, and course of major bleeding in patients with CAT receiving either the DOAC apixaban or the LMWH dalteparin.

The Caravaggio study was a multinational, randomized, open-label, non-inferiority study with blind adjudication of the study outcomes. Patients (n=1,155) with cancer or diagnosed with cancer within 2 years before study inclusion and presenting with symptomatic or incidental proximal lower limb deep vein thrombosis (DVT) or pulmonary embolism (PE) were included. Patients were randomized (1:1) to apixaban, 10 mg orally twice a day for 7 days followed by 5 mg bid or 200 IU/kg dalteparin subcutaneously, daily, for 1 month followed by 150 IU/kg od (maximum daily dose was 18,000 IU). Treatment duration was 6 months. Recurrent venous thromboembolism (VTE) occurred in 5,6% of patients treated with apixaban compared to 7.9% of patients receiving dalteparin (HR 0.63, 95%CI: 0.37-1.07). Major bleeding was present in 3.8% of patients with apixaban and in 4.0% in those treated with dalteparin (HR 0.82, 95%CI: 0.40-1.69) [8].

Major bleeding events were classified using the European Medicines Agency (EMA) definition. These included clinically overt bleeding associated with a decline of ≥2 g/dL in hemoglobin, bleeding that required 2 or more units of blood transfusion, bleeding that occurred at a critical site, fatal bleeding, and bleeding events resulting in surgical intervention. CRNMB events were defined as acute clinically overt bleeding that did not meet the EMA definitions, but required medical intervention by a health caretaker.

Main results


The number of bleedings as well as the clinical presentation and course of major bleeding events in patients treated for CAT were similar in the apixaban and dalteparin treatment groups. These findings were consistent across various cancers, including different gastrointestinal tumor types.


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