Safety and efficacy of direct oral anticoagulants for venous thromboembolism and stroke prophylaxis in patients with hematologic malignancies

Abstract

Purpose

Low-molecular-weight heparins are currently the recommended antithrombotic therapy for treatment and prevention of malignancy-related venous thromboembolism. Currently, the evidence evaluating direct oral anticoagulants versus low-molecular-weight heparins or a vitamin K antagonist in cancer patients with hematologic malignancies is limited. We evaluated the safety and efficacy of direct oral anticoagulants for venous thromboembolism treatment or stroke prevention for non-valvular atrial fibrillation in patients with hematologic malignancies.

Methods

This was a retrospective evaluation of adult patients with hematologic malignancies who received at least one dose of the Food and Drug Administration-approved direct oral anticoagulant for venous thromboembolism treatment or stroke prevention. We determined the frequency of major bleeding events, non-major bleeding events, stroke, systemic embolism, appropriateness of initial direct oral anticoagulant doses, holding practices prior to procedures, and the rate of all-cause mortality. An analysis was also performed to compare the incidence of bleeding between patients with a history of hematopoietic stem cell transplant to non-transplant patients.

Results

A total of 103 patients were identified, with the majority of patients receiving rivaroxaban for venous thromboembolism treatment. Major bleeding events occurred in four patients and no fatal bleeding events occurred. Non-major bleeding occurred in 29 patients, most commonly epistaxis and bruising. Two patients experienced a systemic embolism while on direct oral anticoagulant therapy.

Conclusion

Direct oral anticoagulants may be a safe and effective alternative for anticoagulation therapy in patients with hematologic malignancies. However, larger prospective studies comparing direct oral anticoagulants to low-molecular-weight heparins or vitamin K antagonists are warranted to compare efficacy and safety outcomes in this patient population.

Keywords

Direct oral anticoagulants hematologic malignancy cancer thromboembolism hematopoietic stem cell transplant

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References

Ravikumar R, Lim CS and Davies AH. The role of new oral Anticoagulants (NOACs) in cancer patients. Adv Exp Med Biol 2017; 906: 137–148.

Lee

AYY

Levine

Baker

, et al. Low-molecular-weight heparin versus a coumarin for the prevention of recurrent venous thromboembolism in patients with cancer. N Engl J Med 2003; 349: 146–153.

Lyman

Khorana

Kuderer

Lee

Arcelus

Balaban

, et al. Venous thromboembolism prophylaxis and treatment in patients with cancer: American Society of Clinical Oncology Clinical Practice Guideline Update. J Clin Oncol 2013; 31: 2189–204.

Vedovati

Germini

Agnelli

, et al. Direct oral anticoagulants in patients with VTE and cancer. Chest 2015; 147: 475–483.

Kearon

Akl

Ornelas

, et al. Antithrombotic therapy for VTE disease: CHEST guideline and expert panel report. Chest 2016; 149: 315–352.

Raskob

van Es

Verhamme

, et al. Edoxaban for the treatment of cancer-associated venous thromboembolism. N Engl J Med 2017; 378: 615–624.

Young

Marshall

Thirlwall

, et al. Comparison of an oral factor Xa inhibitor with low molecular weight heparin in patients with cancer with venous thromboembolism: results of a randomized trial (SELECT-D). J Clin Oncol 2018; 36: 2017–2023.

Agnelli

Buller

Cohen

, et al. Oral apixaban for the treatment of acute venous thromboembolism. N Engl J Med 2013; 369: 799–808.

Khorana

Noble

Lee

AYY

, et al. Role of direct oral anticoagulants in the treatment of cancer-associated venous thromboembolism: guidance from the SSC of the ISTH. J Thromb Haemost 2018; 16: 1891–1894.

10.

Khanal

Bociek

Chen

, et al. Venous thromboembolism in patients with hematologic malignancy and thrombocytopenia. Am J Hematol 2016; 91: E468–E472.

11.

Franchini

Frattini

Crestani

, et al. Bleeding complications in patients with hematologic malignancies. Semin Thromb Hemost 2013; 39: 94–100.

12.

Hellwig

Gulseth

. Pharmacokinetic and pharmacodynamic drug interactions with new oral anticoagulants: what do they mean for patients with atrial fibrillation?. Ann Pharmacother 2013; 47: 1478–1487.

13.

Forbes

Polasek

. Potential drug–drug interactions with direct oral anticoagulants in elderly hospitalized patients. Ther Adv Drug Saf 2017; 8: 319–328.

14.

Boehringer Ingelheim Pharmaceuticals Inc. Pradaxa (package insert). Ridgefield: Boehringer Ingelheim Pharmaceuticals Inc, 2017.

15.

Janssen Pharmaceuticals, Inc. Xarelto (package insert). Titusville: Janssen Pharmaceuticals, Inc, 2017.

16.

Pfizer Inc. Eliquis (package insert). New York: Pfizer Inc, 2017.

17.

Daiichi Sankyo Co. Savaysa (package insert). Basking Ridge: Daiichi Sankyo Co, 2017.

18.

Drug Interactions & Labeling. Drug development and drug interactions: table of substrates, inhibitors and inducers, www.fda.gov/drugs/developmentapprovalprocess/developmentresources/druginteractionslabeling/ucm093664.htm (accessed 10 December 2018).

19.

Hansten PD and Horn JR. The top 100 drug interactions: a guide to patient management. 2018th ed. Freeland: H & H Publications.

20.

Salerno

Tsapepas

Papachristos

, et al. Direct oral anticoagulant considerations in solid organ transplantation: A review. Clin Transplant 2016; 31: e12873.

21.

Arber

Orazi

Hasserjian

, et al. The 2016 revision to the World Health Organization classification of myeloid neoplasms and acute leukemia. Blood 2016; 127(20): 2391.

22.

Swerdlow

Campo

Pileri

, et al. The 2016 revision of the World Health Organization classification of lymphoid neoplasms. Blood 2016; 127: 2375.

23.

Man

Morris

Brown

, et al. Use of direct oral anticoagulants in patients on immunomodulatory agents. J Thromb Thrombolysis 2017; 44: 298–302.

24.

Kujovich

. Factor V Leiden thrombophilia. Genet Med 2010; 13: 1.

25.

Bain

. Bone marrow biopsy morbidity: review of 2003. J Clin Pathol 2005; 58: 406.

26.

Dubois

Dincq

A-S

Douxfils

, et al. Perioperative management of patients on direct oral anticoagulants. Thromb J 2017; 15: 14.

27.

Nutescu

. Oral anticoagulant therapies: balancing the risks. Am J Health Syst Pharm 2013; 70: S3.

28.

Doherty

Gluckman

Hucker

, et al. 2017 ACC expert consensus decision pathway for periprocedural management of anticoagulation in patients with nonvalvular atrial fibrillation: a report of the American College of Cardiology Clinical Expert Consensus Document Task Force. J Am Coll Cardiol 2017; 69: 871–898.