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Published in: Journal of Thrombosis and Thrombolysis 4/2017

01-05-2017

Appropriateness of direct oral anticoagulant dosing for venous thromboembolism treatment

Authors: Emmeline Tran, Ashley Duckett, Sarah Fisher, Nicole Bohm

Published in: Journal of Thrombosis and Thrombolysis | Issue 4/2017

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Abstract

Adherence to FDA-approved dosing for the direct oral anticoagulants (DOACs) based on renal function, hepatic function, and concomitant medications in a real-world setting has not been evaluated. The purpose of this retrospective cohort analysis was to determine the prescribing accuracy of DOAC dosing for venous thromboembolism (VTE) treatment compared with enoxaparin. The secondary outcomes were to describe the incidence of in-hospital VTE recurrence and bleeding on DOAC therapy. The study included 168 patients with 261 admissions for the DOAC group and 639 patients with 841 admissions for the enoxaparin group. Dosing was appropriate in 235/261 (90.0%) of patient admissions in the DOAC group. Among the DOAC doses administered, 233/2246 (10.4%) were contraindicated based on renal function, hepatic function, or drug interactions compared with 322/7293 (4.4%) of administered enoxaparin doses evaluated based on renal function, p < 0.001. Three recurrent VTEs, 3 major bleeding events, 1 probable major bleeding event, and 3 clinically relevant non-major bleeding events were observed during the study period. Although a majority of DOAC doses administered were appropriate, further education and close monitoring of these agents are warranted to increase appropriateness of therapy and improve patient safety.
Literature
3.
go back to reference Kearon C, Akl EA, Ornelas J, Blaivas A, Jimenez D, Bounameaux H, Huisman M, King CS, Morris TA, Sood N, Stevens SM, Vintch JR, Wells P, Woller SC, Moores L (2016) Antithrombotic therapy for VTE disease: CHEST guideline and expert panel report. Chest 149(2):315–352. doi:10.1016/j.chest.2015.11.026 CrossRefPubMed Kearon C, Akl EA, Ornelas J, Blaivas A, Jimenez D, Bounameaux H, Huisman M, King CS, Morris TA, Sood N, Stevens SM, Vintch JR, Wells P, Woller SC, Moores L (2016) Antithrombotic therapy for VTE disease: CHEST guideline and expert panel report. Chest 149(2):315–352. doi:10.​1016/​j.​chest.​2015.​11.​026 CrossRefPubMed
5.
go back to reference van der Hulle T, Kooiman J, den Exter PL, Dekkers OM, Klok FA, Huisman MV (2014) Effectiveness and safety of novel oral anticoagulants as compared with vitamin K antagonists in the treatment of acute symptomatic venous thromboembolism: a systematic review and meta-analysis. J Thromb Haemost 12(3):320–328. doi:10.1111/jth.12485 CrossRefPubMed van der Hulle T, Kooiman J, den Exter PL, Dekkers OM, Klok FA, Huisman MV (2014) Effectiveness and safety of novel oral anticoagulants as compared with vitamin K antagonists in the treatment of acute symptomatic venous thromboembolism: a systematic review and meta-analysis. J Thromb Haemost 12(3):320–328. doi:10.​1111/​jth.​12485 CrossRefPubMed
7.
go back to reference Graff J, Harder S (2013) Anticoagulant therapy with the oral direct factor Xa inhibitors rivaroxaban, apixaban and edoxaban and the thrombin inhibitor dabigatran etexilate in patients with hepatic impairment. Clin Pharmacokinet 52(4):243–254. doi:10.1007/s40262-013-0034-0 CrossRefPubMed Graff J, Harder S (2013) Anticoagulant therapy with the oral direct factor Xa inhibitors rivaroxaban, apixaban and edoxaban and the thrombin inhibitor dabigatran etexilate in patients with hepatic impairment. Clin Pharmacokinet 52(4):243–254. doi:10.​1007/​s40262-013-0034-0 CrossRefPubMed
8.
go back to reference Schulman S, Kearon C, Kakkar AK, Mismetti P, Schellong S, Eriksson H, Baanstra D, Schnee J, Goldhaber SZ (2009) Dabigatran versus warfarin in the treatment of acute venous thromboembolism. N Engl J Med 361(24):2342–2352. doi:10.1056/NEJMoa0906598 CrossRefPubMed Schulman S, Kearon C, Kakkar AK, Mismetti P, Schellong S, Eriksson H, Baanstra D, Schnee J, Goldhaber SZ (2009) Dabigatran versus warfarin in the treatment of acute venous thromboembolism. N Engl J Med 361(24):2342–2352. doi:10.​1056/​NEJMoa0906598 CrossRefPubMed
9.
go back to reference Schulman S, Kakkar AK, Goldhaber SZ, Schellong S, Eriksson H, Mismetti P, Christiansen AV, Friedman J, Le Maulf F, Peter N, Kearon C (2014) Treatment of acute venous thromboembolism with dabigatran or warfarin and pooled analysis. Circulation 129(7):764–772. doi:10.1161/CIRCULATIONAHA.113.004450 CrossRefPubMed Schulman S, Kakkar AK, Goldhaber SZ, Schellong S, Eriksson H, Mismetti P, Christiansen AV, Friedman J, Le Maulf F, Peter N, Kearon C (2014) Treatment of acute venous thromboembolism with dabigatran or warfarin and pooled analysis. Circulation 129(7):764–772. doi:10.​1161/​CIRCULATIONAHA.​113.​004450 CrossRefPubMed
10.
go back to reference Bauersachs R, Berkowitz SD, Brenner B, Buller HR, Decousus H, Gallus AS, Lensing AW, Misselwitz F, Prins MH, Raskob GE, Segers A, Verhamme P, Wells P, Agnelli G, Bounameaux H, Cohen A, Davidson BL, Piovella F, Schellong S (2010) Oral rivaroxaban for symptomatic venous thromboembolism. N Engl J Med 363(26):2499–2510. doi:10.1056/NEJMoa1007903 CrossRefPubMed Bauersachs R, Berkowitz SD, Brenner B, Buller HR, Decousus H, Gallus AS, Lensing AW, Misselwitz F, Prins MH, Raskob GE, Segers A, Verhamme P, Wells P, Agnelli G, Bounameaux H, Cohen A, Davidson BL, Piovella F, Schellong S (2010) Oral rivaroxaban for symptomatic venous thromboembolism. N Engl J Med 363(26):2499–2510. doi:10.​1056/​NEJMoa1007903 CrossRefPubMed
11.
go back to reference Buller HR, Prins MH, Lensin AW, Decousus H, Jacobson BF, Minar E, Chlumsky J, Verhamme P, Wells P, Agnelli G, Cohen A, Berkowitz SD, Bounameaux H, Davidson BL, Misselwitz F, Gallus AS, Raskob GE, Schellong S, Segers A (2012) Oral rivaroxaban for the treatment of symptomatic pulmonary embolism. N Engl J Med 366(14):1287–1297. doi:10.1056/NEJMoa1113572 CrossRefPubMed Buller HR, Prins MH, Lensin AW, Decousus H, Jacobson BF, Minar E, Chlumsky J, Verhamme P, Wells P, Agnelli G, Cohen A, Berkowitz SD, Bounameaux H, Davidson BL, Misselwitz F, Gallus AS, Raskob GE, Schellong S, Segers A (2012) Oral rivaroxaban for the treatment of symptomatic pulmonary embolism. N Engl J Med 366(14):1287–1297. doi:10.​1056/​NEJMoa1113572 CrossRefPubMed
12.
go back to reference Agnelli G, Buller HR, Cohen A, Curto M, Gallus AS, Johnson M, Masiukiewicz U, Pak R, Thompson J, Raskob GE, Weitz JI (2013) Oral apixaban for the treatment of acute venous thromboembolism. N Engl J Med 369(9):799–808. doi:10.1056/NEJMoa1302507 CrossRefPubMed Agnelli G, Buller HR, Cohen A, Curto M, Gallus AS, Johnson M, Masiukiewicz U, Pak R, Thompson J, Raskob GE, Weitz JI (2013) Oral apixaban for the treatment of acute venous thromboembolism. N Engl J Med 369(9):799–808. doi:10.​1056/​NEJMoa1302507 CrossRefPubMed
13.
go back to reference Buller HR, Decousus H, Grosso MA, Mercuri M, Middeldorp S, Prins MH, Raskob GE, Schellong SM, Schwocho L, Segers A, Shi M, Verhamme P, Wells P (2013) Edoxaban versus warfarin for the treatment of symptomatic venous thromboembolism. N Engl J Med 369(15):1406–1415. doi:10.1056/NEJMoa1306638 CrossRefPubMed Buller HR, Decousus H, Grosso MA, Mercuri M, Middeldorp S, Prins MH, Raskob GE, Schellong SM, Schwocho L, Segers A, Shi M, Verhamme P, Wells P (2013) Edoxaban versus warfarin for the treatment of symptomatic venous thromboembolism. N Engl J Med 369(15):1406–1415. doi:10.​1056/​NEJMoa1306638 CrossRefPubMed
17.
go back to reference Tellor KB, Patel S, Armbruster AL, Daly MW (2015) Evaluation of the appropriateness of dosing, indication and safety of rivaroxaban in a community hospital. J Clin Pharm Ther 40(4):447–451. doi:10.1111/jcpt.12288 CrossRefPubMed Tellor KB, Patel S, Armbruster AL, Daly MW (2015) Evaluation of the appropriateness of dosing, indication and safety of rivaroxaban in a community hospital. J Clin Pharm Ther 40(4):447–451. doi:10.​1111/​jcpt.​12288 CrossRefPubMed
18.
go back to reference Trujillo-Santos J, Di Micco P, Dentali F, Douketis J, Diaz-Peromingo JA, Nunez MJ, Canas I, Mastroiacovo D, Saraiva de Sousa M, Monreal M (2016) Real-life treatment of venous thromboembolism with direct oral anticoagulants: the influence of recommended dosing and regimens. Thromb Haemost. doi:10.1160/TH16-07-0494 PubMed Trujillo-Santos J, Di Micco P, Dentali F, Douketis J, Diaz-Peromingo JA, Nunez MJ, Canas I, Mastroiacovo D, Saraiva de Sousa M, Monreal M (2016) Real-life treatment of venous thromboembolism with direct oral anticoagulants: the influence of recommended dosing and regimens. Thromb Haemost. doi:10.​1160/​TH16-07-0494 PubMed
19.
go back to reference Janssen Pharmaceuticals (2016) Rivaroxaban (Xarelto®) tablets, for oral use [product information]. Janssen Pharmaceuticals Inc., Titusville Janssen Pharmaceuticals (2016) Rivaroxaban (Xarelto®) tablets, for oral use [product information]. Janssen Pharmaceuticals Inc., Titusville
20.
go back to reference Bristol-Myers Squibb Company (2016). Apixaban (Eliquis®) tablets, for oral use [product information]. Bristol-Myers Squibb Company, Princeton Bristol-Myers Squibb Company (2016). Apixaban (Eliquis®) tablets, for oral use [product information]. Bristol-Myers Squibb Company, Princeton
21.
go back to reference Boehringer Ingelheim Pharmaceuticals (2015). Dabigatran (Pradaxa®) capsules, for oral use [product information]. Boehringer Ingelheim Pharmaceuticals, Inc., Ridgefield Boehringer Ingelheim Pharmaceuticals (2015). Dabigatran (Pradaxa®) capsules, for oral use [product information]. Boehringer Ingelheim Pharmaceuticals, Inc., Ridgefield
22.
go back to reference Daiichi Sankyo (2016) Edoxaban (Savaysa®) tablets, for oral use [product information]. Daiichi Sankyo, Inc., Parisippany Daiichi Sankyo (2016) Edoxaban (Savaysa®) tablets, for oral use [product information]. Daiichi Sankyo, Inc., Parisippany
24.
go back to reference Schmid P, Fischer AG, Wuillemin WA (2009) Low-molecular-weight heparin in patients with renal insufficiency. Swiss Med Wkly 139(31–32):438–452PubMed Schmid P, Fischer AG, Wuillemin WA (2009) Low-molecular-weight heparin in patients with renal insufficiency. Swiss Med Wkly 139(31–32):438–452PubMed
26.
go back to reference Nutescu EA, Spinler SA, Wittkowsky A, Dager WE (2009) Low-molecular-weight heparins in renal impairment and obesity: available evidence and clinical practice recommendations across medical and surgical settings. Ann Pharmacother 43(6):1064–1083. doi:10.1345/aph.1L194 CrossRefPubMed Nutescu EA, Spinler SA, Wittkowsky A, Dager WE (2009) Low-molecular-weight heparins in renal impairment and obesity: available evidence and clinical practice recommendations across medical and surgical settings. Ann Pharmacother 43(6):1064–1083. doi:10.​1345/​aph.​1L194 CrossRefPubMed
27.
go back to reference Davidson BL, Verheijen S, Lensing AW, Gebel M, Brighton TA, Lyons RM, Rehm J, Prins MH (2014) Bleeding risk of patients with acute venous thromboembolism taking nonsteroidal anti-inflammatory drugs or aspirin. JAMA Intern Med 174 (6):947–953. doi:10.1001/jamainternmed.2014.946 CrossRefPubMed Davidson BL, Verheijen S, Lensing AW, Gebel M, Brighton TA, Lyons RM, Rehm J, Prins MH (2014) Bleeding risk of patients with acute venous thromboembolism taking nonsteroidal anti-inflammatory drugs or aspirin. JAMA Intern Med 174 (6):947–953. doi:10.​1001/​jamainternmed.​2014.​946 CrossRefPubMed
29.
go back to reference Sanofi-Aventis (2013) Enoxparin (Lovenox®) injection, for subcutaneous and intravenous use [product information]. Sanofi-Aventis LLC, Bridgewater Sanofi-Aventis (2013) Enoxparin (Lovenox®) injection, for subcutaneous and intravenous use [product information]. Sanofi-Aventis LLC, Bridgewater
Metadata
Title
Appropriateness of direct oral anticoagulant dosing for venous thromboembolism treatment
Authors
Emmeline Tran
Ashley Duckett
Sarah Fisher
Nicole Bohm
Publication date
01-05-2017
Publisher
Springer US
Published in
Journal of Thrombosis and Thrombolysis / Issue 4/2017
Print ISSN: 0929-5305
Electronic ISSN: 1573-742X
DOI
https://doi.org/10.1007/s11239-017-1487-z

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