New Oral Anticoagulants in Patients with Nonvalvular Atrial Fibrillation: a Review of Pharmacokinetics, Safety, Efficacy, Quality of Life, and Cost Effectiveness

Overview

Journal Drug Des Devel Ther

Specialty Pharmacology

Date 2014 Jun 28

PMID 24970997

Citations 33

Authors

Helen Mani

Edelgard Lindhoff-Last

Affiliations

Soon will be listed here.

Abstract

Atrial fibrillation (AF) continues to be a leading cause of cerebrovascular morbidity and mortality resulting from cardioembolic stroke. Oral anticoagulation therapy has been shown to decrease the incidence of cardioembolic stroke in patients with AF by more than 50%. Appropriate use of anticoagulation with vitamin K antagonists requires precise adherence and monitoring. A number of factors that potentially induce patients' dissatisfaction reduce quality of patient life. New direct oral anticoagulants, such as the direct factor Xa inhibitors rivaroxaban, apixaban, edoxaban, and the thrombin inhibitor dabigatran, were developed to overcome the limitations of the conventional anticoagulant drugs. However, models to optimize the benefit of therapy and to ensure that therapy can be safely continued are missing for the new oral anticoagulants. This review will briefly describe the new oral anticoagulants dabigatran, rivaroxaban, apixaban, and edoxaban with focus on their use for prevention of embolic events in AF. Moreover, it will discuss the safety, efficacy, cost data, and benefit for patients' quality of life and adherence.

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References

Legrand M, Mateo J, Aribaud A, Ginisty S, Eftekhari P, Tran Ba Huy P . The use of dabigatran in elderly patients. Arch Intern Med. 2011; 171(14):1285-6. DOI: 10.1001/archinternmed.2011.314. View

Mani H, Kasper A, Lindhoff-Last E . Measuring the anticoagulant effects of target specific oral anticoagulants-reasons, methods and current limitations. J Thromb Thrombolysis. 2013; 36(2):187-94. DOI: 10.1007/s11239-013-0907-y. View

Mismetti P, Laporte S . New oral antithrombotics: a need for laboratory monitoring. For. J Thromb Haemost. 2010; 8(4):621-6. DOI: 10.1111/j.1538-7836.2010.03764.x. View

Wienen W, Stassen J, Priepke H, Ries U, Hauel N . In-vitro profile and ex-vivo anticoagulant activity of the direct thrombin inhibitor dabigatran and its orally active prodrug, dabigatran etexilate. Thromb Haemost. 2007; 98(1):155-62. View

Ansell J, Hirsh J, Poller L, Bussey H, Jacobson A, Hylek E . The pharmacology and management of the vitamin K antagonists: the Seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy. Chest. 2004; 126(3 Suppl):204S-233S. DOI: 10.1378/chest.126.3_suppl.204S. View

Mani H, Hesse C, Stratmann G, Lindhoff-Last E . Rivaroxaban differentially influences ex vivo global coagulation assays based on the administration time. Thromb Haemost. 2011; 106(1):156-64. DOI: 10.1160/TH10-10-0667. View

Gadisseur A, Kaptein A, Breukink-Engbers W, van der Meer F, Rosendaal F . Patient self-management of oral anticoagulant care vs. management by specialized anticoagulation clinics: positive effects on quality of life. J Thromb Haemost. 2004; 2(4):584-91. DOI: 10.1111/j.1538-7836.2004.00659.x. View

Casais P, Meschengieser S, Sanchez-Luceros A, Lazzari M . Patients' perceptions regarding oral anticoagulation therapy and its effect on quality of life. Curr Med Res Opin. 2005; 21(7):1085-90. DOI: 10.1185/030079905X50624. View

Friberg L, Rosenqvist M, Lip G . Evaluation of risk stratification schemes for ischaemic stroke and bleeding in 182 678 patients with atrial fibrillation: the Swedish Atrial Fibrillation cohort study. Eur Heart J. 2012; 33(12):1500-10. DOI: 10.1093/eurheartj/ehr488. View

10.

Samama M, Contant G, Spiro T, Perzborn E, Guinet C, Gourmelin Y . Evaluation of the anti-factor Xa chromogenic assay for the measurement of rivaroxaban plasma concentrations using calibrators and controls. Thromb Haemost. 2011; 107(2):379-87. DOI: 10.1160/TH11-06-0391. View

11.

Schiele F, van Ryn J, Canada K, Newsome C, Sepulveda E, Park J . A specific antidote for dabigatran: functional and structural characterization. Blood. 2013; 121(18):3554-62. DOI: 10.1182/blood-2012-11-468207. View

12.

Albers G, Dalen J, Laupacis A, Manning W, Petersen P, Singer D . Antithrombotic therapy in atrial fibrillation. Chest. 2001; 119(1 Suppl):194S-206S. DOI: 10.1378/chest.119.1_suppl.194s. View

13.

Ogata K, Mendell-Harary J, Tachibana M, Masumoto H, Oguma T, Kojima M . Clinical safety, tolerability, pharmacokinetics, and pharmacodynamics of the novel factor Xa inhibitor edoxaban in healthy volunteers. J Clin Pharmacol. 2010; 50(7):743-53. DOI: 10.1177/0091270009351883. View

14.

Mueck W, Schwers S, Stampfuss J . Rivaroxaban and other novel oral anticoagulants: pharmacokinetics in healthy subjects, specific patient populations and relevance of coagulation monitoring. Thromb J. 2013; 11(1):10. PMC: 3726366. DOI: 10.1186/1477-9560-11-10. View

15.

Samsa G, Matchar D . Relationship between test frequency and outcomes of anticoagulation: a literature review and commentary with implications for the design of randomized trials of patient self-management. J Thromb Thrombolysis. 2000; 9(3):283-92. DOI: 10.1023/a:1018778914477. View

16.

Naccarelli G, Panaccio M, Cummins G, Tu N . CHADS2 and CHA2DS2-VASc risk factors to predict first cardiovascular hospitalization among atrial fibrillation/atrial flutter patients. Am J Cardiol. 2012; 109(10):1526-33. DOI: 10.1016/j.amjcard.2012.01.371. View

17.

Lu G, DeGuzman F, Hollenbach S, Karbarz M, Abe K, Lee G . A specific antidote for reversal of anticoagulation by direct and indirect inhibitors of coagulation factor Xa. Nat Med. 2013; 19(4):446-51. DOI: 10.1038/nm.3102. View

18.

Krejczy M, Harenberg J, Marx S, Obermann K, Frolich L, Wehling M . Comparison of cost-effectiveness of anticoagulation with dabigatran, rivaroxaban and apixaban in patients with non-valvular atrial fibrillation across countries. J Thromb Thrombolysis. 2013; 37(4):507-23. DOI: 10.1007/s11239-013-0989-6. View

19.

Lauritzen B, Hedner U, Johansen P, Tranholm M, Ezban M . Recombinant human factor VIIa and a factor VIIa-analogue reduces heparin and low molecular weight heparin (LMWH)-induced bleeding in rats. J Thromb Haemost. 2008; 6(5):804-11. DOI: 10.1111/j.1538-7836.2008.02933.x. View

20.

Stangier J, Clemens A . Pharmacology, pharmacokinetics, and pharmacodynamics of dabigatran etexilate, an oral direct thrombin inhibitor. Clin Appl Thromb Hemost. 2009; 15 Suppl 1:9S-16S. DOI: 10.1177/1076029609343004. View