Patient-reported outcomes associated with changing to rivaroxaban for the treatment of cancer-associated venous thromboembolism - The COSIMO study.

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Venous thromboembolism treatment in patients with cancer: reflections on an evolving landscape

Cancer is a leading cause of morbidity and mortality worldwide. It is also one of the strongest risk factors for venous thromboembolism (VTE), reported in approximately 20% of all cases of VTE diagnosed. The thrombotic effect of cancer and its treatments, however, is highly variable among patients and changes over the course of their cancer. Anticoagulant therapy remains the cornerstone of VTE treatment, but it is associated with a substantial rate of VTE recurrence and the potential for serious bleeding. The risk of bleeding in patients with cancer is also dependent on the cancer type and its treatments, often revealing underlying tumor invasion of mucosal or parenchymal tissues, and treatment complications such as thrombocytopenia or coagulopathy. Over the past few decades, efforts to improve the efficacy and safety of anticoagulant therapy for the treatment and prevention of cancer-associated thromboembolism have resulted in changes in the standard of practice. This evolution has been made possible largely through the development of new anticoagulants. This review will reflect on the major advances in the treatment of cancer-associated thrombosis and offer insights on how to address unmet needs in this field

Vaccine‐induced prothrombotic immune thrombocytopenia without thrombosis may not require immune modulatory therapy: A case report

Abstract Background Vaccine‐induced immune thrombotic thrombocytopenia (VITT) is a rare complication of the ChAdOx1 nCoV‐19 and Ad26.COV2.S COVID‐19 vaccines. It presents most commonly with severe thrombocytopenia and thrombotic complications with extremely high D‐dimer levels 5–30 days after vaccination. We report a patient who presented with mild thrombocytopenia and minimally elevated D‐dimer levels without thrombosis, but who tested positive for antiplatelet factor 4 (PF4) platelet‐activating antibodies on a PF4‐enhanced serotonin‐release assay. Key Clinical Question Is immunomodulation necessary in patients who present without thrombosis? Clinical Approach and Conclusions Treatment with rivaroxaban alone was followed by platelet normalization despite persistence of anti‐PF4 antibodies. This case provides support that vaccination for COVID‐19 can induce a broad, heterogeneous prothrombotic disorder characterized by anti‐PF4 platelet‐activating antibodies that shares features with classical heparin‐induced thrombocytopenia (HIT) and autoimmune HIT syndromes and that immunomodulation may not be required in those without thrombosis

LBA-2 A randomized trial of long-term tinzaparin, a Low Molecular Weight Heparin (LMWH), versus warfarin for treatment of acute venous thromboembolism (VTE) in cancer patients-the CATCH study

Background Patients with cancer and VTE have a substantial risk of recurrent VTE. LMWH reduces the risk of symptomatic, recurrent VTE compared with warfarin and is recommended as the preferred anticoagulant by consensus guidelines. However, the evidence is based largely on a single, open-label randomized trial (CLOT; Lee et al NEJM 2003). Warfarin is still often used for the treatment of VTE in cancer patients worldwide. Methods The primary objective of this randomized, open-label, multicenter, Phase III trial (CATCH; NCT01130025) was to assess the efficacy of tinzaparin in preventing recurrent VTE in patients with active cancer and acute, symptomatic proximal deep vein thrombosis (DVT) and/or pulmonary embolism (PE). Patients were randomized (stratified by geographic region, tumor characteristic [distant metastasis, no distant metastasis, hematological malignancy] and history of VTE) to receive tinzaparin 175 IU/kg once daily for 6 months or initial tinzaparin 175 IU/kg once daily for 5 10 days overlapped and followed by dose-adjusted warfarin (target INR 2.0 3.0) for 6 months. The primary efficacy outcome was time to recurrent VTE verified by objective, standard imaging and blinded central adjudication; this was a composite primary endpoint that included symptomatic DVT and/or PE, incidental proximal DVT and/or PE and fatal PE. The primary safety endpoint was incidence of major bleeding. All patients were followed up to 6 months or death, whichever came sooner. Blinded central adjudication was also performed for all bleeding events and causes of death. A proportional hazards model for competing risks was applied to all randomized patients, treating all non-VTE-related deaths as competing events. An independent Data Safety Monitoring Board reviewed safety data at regular intervals. Results Nine hundred patients were included from 165 sites in 32 countries across 5 continents. Of these, 449 were randomized to tinzaparin and 451 to warfarin. Mean age was 59 years (range 18 89); 59% female. A total of 77% of patients had a baseline ECOG performance status (PS) of 0 1 and 23% had a PS of 2. The most common primary tumor sites were gynecologic (23%), colorectal (13%), lung (12%), breast (9%); 10% had hematological malignancies. At the time of randomization, metastatic disease was present in 55% of patients and 44% had received prior cancer treatment (chemotherapy, surgery and/or radiation). Time-in-therapeutic range was 47% in the warfarin arm, with 27% above and 26% below the range. Over the 6-month trial period, 31 patients (6.9%) in the tinzaparin arm experienced recurrent VTE compared with 45 (10%) in the warfarin arm (hazard ratio [HR] 0.65 [95% CI 0.41 1.03; P=0.07]) (see figure). There were 2 patients with incidental VTE, both were in the warfarin arm. Symptomatic non-fatal DVT occurred in 12 patients (2.7%) in the tinzaparin arm and 24 (5.3%) in the warfarin arm (HR 0.48 [95% CI 0.24 0.96]; P=0.04). Symptomatic non-fatal PE occurred in 3 patients in the tinzaparin arm and 2 in the warfarin arm; fatal PE occurred in 17 (3.8%) patients in each arm (HR 0.96 [95% CI 0.49 1.88]; P=0.90). There was no difference in the incidence of major bleeding events (n=13 [2.9%] in the tinzaparin arm and 12 [2.7%] in the warfarin arm), but significantly fewer patients experienced clinically relevant non-major bleeding with tinzaparin than warfarin (50 [11%] and 73 [16%] patients, respectively; P=0.03). No difference in mortality was seen with 6-month survival rates of 59% and 60%, respectively. Conclusions In cancer patients with symptomatic VTE, tinzaparin lowered the risk of recurrent VTE compared with warfarin, with a significant reduction in symptomatic DVT and clinically relevant non-major bleeding. No difference in major bleeding or overall mortality was observed. (Figure Presented)