Novel Oral Anti-coagulants in Patients with Malignancy Lori-Ann Linkins, MD, MSc(Clin Epi), FRCPC McMaster University, Hamilton, ON
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1 Novel Oral Anti-coagulants in Patients with Malignancy Lori-Ann Linkins, MD, MSc(Clin Epi), FRCPC McMaster University, Hamilton, ON
2 Disclosures Speaker honorarium from Bayer (rivaroxaban; Xarelto) and Pfizer (dalteparin; Fragmin) Research funding from Bayer for a study evaluating rivaroxaban for treatment of HIT
3 Novel Oral Anticoagulants in Patients with Malignancy Dabigatran (Pradaxa) Rivaroxaban (Xarelto) Apixaban (Eliquis) Edoxaban (not yet available) Terminology: NOAC = DOAC
4 Novel Oral Anticoagulants in Patients with Malignancy Dabigatran (Pradaxa), Rivaroxaban (Xarelto), Apixaban (Eliquis) Approved in Canada for: thromboprophylaxis following THR and TKR prevention of stroke in patients with afib treatment of acute DVT/PE and prevention of recurrent DVT/PE
5 Efficacy of NOACs in Cancer Patient Subgroups NOAC Comparator Number of NOAC Patients Risk of Recurrent VTE (%) NOAC Warfarin Dabigatran Warfarin Rivaroxaban Enox/Warfarin Apixaban Enox/Warfarin VTE, venous thromboembolism Total 608 Schulman et al,th 2015; Prins et al, Lancet Hematol 2014; Agnelli et al, Eur Heart H, 2014
6 Safety of NOACs in Cancer Patient Subgroups NOAC Comparator Number of NOAC Patients Risk of Major Bleed (%) NOAC Warfarin Dabigatran Warfarin Rivaroxaban Enox/Warfarin Apixaban Enox/Warfarin Total 593 Schulman et al,th 2015; Prins et al, Lancet Hematol 2014; Agnelli et al, Eur Heart H, 2014
7 Meta-Analysis of NOACs in Cancer: Recurrent VTE Apixaban Rivaroxaban Edoxaban Dabigatran OR 0.63; 95% CI, Vedovati et al., Chest 2015;147;
8 Meta-Analysis of NOACs in Cancer: Bleeding Apixaban Rivaroxaban Edoxaban Dabigatran OR 0.77; 95% CI, Vedovati et al., Chest 2015;147;
9 Novel Oral Anticoagulants in Patients with Malignancy NOACs appear to be at least as effective and safe as warfarin for treatment of VTE in patients with malignancy However...
10 Novel Oral Anticoagulants in Patients with Malignancy Only a small proportion of patients in the NOAC clinical trials had cancer (2-6%) Definitions of active cancer differed between studies; patients were highly selected Comparator was warfarin, not LMWH (standard of care)
11 Novel Oral Anticoagulants in Patients with Malignancy Dependent on GI absorption Anticoagulant levels are not easily monitored No specific antidotes to reverse anticoagulant effect in emergent settings Cost can be a factor May interact with antineoplastic agents
12 NOAC Drug Interactions Inducers (may reduce DOAC plasma levels) Inhibitors (may increase DOAC plasma effect) CYP 3A4* P-gp Chemotherapy: paclitaxel Targeted therapies: vemurafenib Hormonal therapies: enzalutamide Immune modulators: dexamethasone, prednisone Chemotherapies: Several anti-mitotic agents, etoposide, doxorubicin, idarubicin, cyclophosphamide, ifosphamide, lomustine Targeted therapies: imatinib, crizotinib and other tyrosine kinase inhibitors Hormonal therapies: tamoxifen, anastrozole, bicalutamide, abiraterone Immunomodulators: cyclosporine, sirolimus, temsirolimus & tacrolimus Supportive care: aprepitant, fosaprepitant, fentanyl, methadone, acetaminophen Source: adapted from: Short NJ, Connors JM. The Oncologist 2014; Lee AYY et al. Blood Chemotherapy: vinblastine, doxorubicin Immunomodulators: dexamethasone Targeted therapies: imatinib, nilotinib, lapatinib, sunitinib, crizotinib, vandetanib Hormonal therapies: tamoxifen, enzalutamide, abiraterone Immunomodulators: cyclosporine, temsirolimus, tacrolimus
13 Novel Oral Anticoagulants in Patients with Malignancy Consensus statement from Canadian experts: We do not recommend the use of the DOACs for acute treatment of cancer-associated thrombosis Carrier et al, Curr Oncology 2015
14 Novel Oral Anticoagulants in Patients with Malignancy My approach: Consider NOAC if treated for at least one month with LMWH and no potential interactions Prefer to continue LMWH if still receiving chemo even if no documented interaction Take quality of life into account on case-bycase basis
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