Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

Keynote webinar | Spotlight on medication adherence

LIVE: Thursday 27th June 2024, 18:00-19:30 (CEST)
Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.
ADVANCED SEARCH
Log in
Top
Journal of Thrombosis and Thrombolysis
Published in: Journal of Thrombosis and Thrombolysis 3/2011

01-04-2011

New oral anticoagulants

Authors: Taki Galanis, Lynda Thomson, Michael Palladino, Geno J. Merli

Published in: Journal of Thrombosis and Thrombolysis | Issue 3/2011

Login to get access

Abstract

The new oral anticoagulants may prove to be one of the most significant innovations in clinical practice in the past 60 years. Apixaban and rivaroxaban are specific inhibitors of Factor Xa while dabigatran inhibits Factor IIa. The predictable pharmacological profile of these new agents will allow physicians to use these drugs without the need for routine coagulation monitoring which is the mainstay of warfarin therapy. In addition, these new agents have not been shown to have any food interactions and limited drug–drug interactions due to their minimal metabolism through the CYP450 system. This unique pharmacokinetic profile may usher in for clinicians a new era of managing thromboembolic disorders. In this paper, the pharmacology of these new oral anticoagulants are reviewed along with the major clinical trials in venous thromboembolism prevention in total hip and knee replacement orthopedic surgery, the treatment of venous thromboembolic disorders and stroke prevention in atrial fibrillation.
Literature
1.
Raghavan N, Frost CE, Yu Z et al (2009) Apixaban metabolism and pharmacokinetics after oral administration to humans. Drug Metab Dispos 37:74–81PubMedCrossRef
2.
Jiang X, Crain EJ, Luettgen JM et al (2009) Apixaban, an oral direct factor Xa inhibitor, inhibitis human clot-bound factor Xa activity in vitro. Thromb Haemost 101:780–782PubMed
3.
Luettgen JM, Wang Z, Seiffer DA, et al (2007) Inhibition of measured thrombin generation in human plasma by Apixaban: a predictive mathematical model based on experimentally determined rate constants. J Thromb Haemost 5(Suppl 2):p-T-633
4.
Frost C, Yu Z, Moore K, et al (2007) Apixaban, an oral direct factor Xa inhibitor: multiple-dose safety, pharmacokinetics and pharmacodynamics in healthy subjects. J Thromb Haemost 5:P-M-664
5.
Kubitza D, Becka M, Wensing G et al (2005) Safety, pharmacodynamics, and pharmacokinetics of BAY 59-7939: an oral, direct Factor Xa inhibitor after multiple dosing in healthy male subjects. Eur J Clin Pharmacol 61:873–880PubMedCrossRef
6.
Kubitza D, Becka M, Voith B et al (2005) Safety, pharmacodynamics, and pharmacokinetics of single doses of BAY 59-7939, an oral, direct Factor Xa inhibitor. Clin Pharmacol Ther 78:412–421PubMedCrossRef
7.
Weinz C, Schwartz T, Kubitza D et al (2009) Metabolism and excretion of rivaroxaban, an oral, direct Factor Xa inhibitor, in rats, dogs, and humans. Drug Metab Dispos 37:1056–1064PubMedCrossRef
8.
Perzborn E, Strassburger J, Wilmen A et al (2005) In vitro and in vivo studies of the novel antithrombotic agent BAY 59-7939, an oral, direct Factor Xa inhibitor. J Thromb Haemost 3:514–521PubMedCrossRef
9.
Ufer M (2010) Comparative efficacy and safety of the novel oral anticoagulants dabigatran, rivaroxaban and apixaban in preclinical and clinical development. Thromb Haemost 103:572–585PubMed
10.
Stangier J, Rathgen K, Stahle H et al (2007) The pharmacokinetics, pharmacodynamics and tolerability of dabigatran etexilate, a new oral direct thrombin inhibitor, in healthy male subjects. Br J Clin Pharmacol 64:292–303PubMedCrossRef
11.
Stangier J, Rathgen K, Stahle H et al (2008) Pharmacokinetics and pharmacodynamics of the direct oral thrombin inhibitor dabigatran in healthy elderly subjects. Clin Pharmacokinet 47:47–59PubMedCrossRef
12.
13.
Van Ryn J, Stangier J, Naertter S, et al (2010) Dabigatran etexilate – a novel, reversible, oral direct thrombin inhibitor: interpretation of coagulation assays and reversal of anticoagulant activity. Thrombo Haemost 103:1116–1127
14.
Kubitza D, Becka M, Zuehlsdorf M et al (2006) Effects of food, an antacid, and the H2 antagonist ranitidine on the absorption of BAY 59-7939 (rivaroxaban), an oral direct Factor Xa inhibitor, in healthy subjects. J Clin Pharmacol 46:549–558PubMedCrossRef
15.
Stangier J, Eriksson BI, Dahl OE et al (2005) Pharmacokinetic profile of the oral direct thrombin inhibitor dabigatran etexilate in healthy subjects and patients undergoing total hip replacement. J Clin Pharmacol 45:555–563PubMedCrossRef
16.
Stangier J, Rathgen K, Stahle H et al (2009) Coadministration of dabigatran etexilate and atorvastatin: assessment of potential impact on pharmacokinetics and pharmacodynamics. Am J Cardiovasc Drugs 9:59–68PubMed
17.
Kubitza D, mueck W, Becka M (2008) No interaction between rivaroxaban—a novel, oral, direct Factor Xa- and atorvastatin. In: Poster P062 presented at the 20th international congress on thrombosis (ICT), Athens, Greece 25–28 June 2008
18.
Walenga JM, Adiguzel C (2010) Drug and dietary interactions of the new oral anticoagulants. Int J Clin Pract 64:956–967PubMedCrossRef
19.
Stangier J, Stahle H, Rathgen K, et al (2007) No interaction of the oral direct thrombin inhibitor dabigatran etexilate and digoxin (abstract). J Thromb Haemost 5(52):abstract P-W 672
20.
21.
22.
Lassen MR, Raskob GE, Gallus A, Pineo G, Chen D, Portman RJ (2009) Apixaban or enoxaparin for thromboprophylaxis after knee replacement. N Eng J Med 361:594–604CrossRef
23.
Lassen MR, Raskob GE, Gallus A, Pineo G, Chen D, Hornick P (2010) ADVANCE-2 Investigators. Apixaban versus enoxaparin for thromboprophylaxis after knee replacement (ADVANCE-2): a randomised double-blind trial. Lancet 375:807–815PubMedCrossRef
24.
Turpie AG, Fisher WD, Bauer KA, Kwong LM, Irwin MW, Kalebo P, Misselwitz F, Gent M (2005) BAY 59-7939: an oral, direct factor Xa inhibitor for the prevention of venous thromboembolism in patients after total knee replacement: a phase II dose-ranging study. J Thromb Haemost 3:2479–2486PubMedCrossRef
25.
Eriksson BI, Borris LC, Dahl OE, Haas S, Huisman MV, Kakkar AK, Muehlhofer E, Dierig C, Misselwitz F, Kalebo P (2006) A once-daily, oral, direct factor Xa inhibitor, rivaroxaban (BAY 59-7939), for thromboprophylaxis after total hip replacement. Circulation 114:2374–2381PubMedCrossRef
26.
Eriksson BI, Borris L, Dahl OE, Haas S, Huisman MV, Kakkar AK, Misselwitz F, Kalebo P (2006) Oral, direct factor Xa inhibition with BAY 59-7939 for the prevention of venous thromboembolism after total hip replacement. J Thromb Haemost 4:121–128PubMedCrossRef
27.
Eriksson BI, Borris LC, Friedman RJ, Haas S, Huisman MV, Kakkar AK, Bandel TJ, Beckmann H, Muehlhofer E, Misselwitz F, Geerts W (2008) Rivaroxaban versus enoxaparin for thromboprophylaxis after hip arthroplasty. N Engl J Med 358:2765–2775PubMedCrossRef
28.
Lassen MR, Ageno W, Borris LC, Lieberman JR, Rosencher N, Bandel TJ, Misselwitz F, Turpie AG (2008) Rivaroxaban versus enoxaparin for thromboprophylaxis after total knee arthroplasty. N Engl J Med 358:2776–2786PubMedCrossRef
29.
Kakkar AK, Brenner B, Dahl OE, Eriksson BI, Mouret P, Muntz J, Soglian AG, Pap AF, Misselwitz F, Haas S (2008) Extended duration rivaroxaban versus short-term enoxaparin for the prevention of venous thromboembolism after total hip arthroplasty: a double-blind, randomised controlled trial. Lancet 372:31–39PubMedCrossRef
30.
Turpie AG, Lassen MR, Davidson BL, Bauer KA, Gent M, Kwong LM, Cushner FD, Lotke PA, Berkowitz SD, Bandel TJ, Benson A, Misselwitz F, Fisher WD (2009) Rivaroxaban versus enoxaparin for thromboprophylaxis after total knee arthroplasty (RECORD4): a randomised trial. Lancet 373:1673–1680PubMedCrossRef
31.
Eriksson BI, Dahl OE, Rosencher N, Kurth AA, van Dijk CN, Frostick SP, Kalebo P, Christiansen AV, Hantel S, Hettiarachchi R, Schnee J, Buller HR (2007) Oral dabigatran etexilate vs. subcutaneous enoxaparin for the prevention of venous thromboembolism after total knee replacement: the RE-MODEL randomized trial. J Thromb Haemost 5:2178–2185PubMedCrossRef
32.
Eriksson BI, Dahl OE, Rosencher N, Kurth AA, van Dijk CN, Frostick SP, Prins MH, Hettiarachchi R, Hantel S, Schnee J, Buller HR (2007) Dabigatran etexilate versus enoxaparin for prevention of venous thromboembolism after total hip replacement: a randomised, double-blind, non-inferiority trial. Lancet 370:949–956PubMedCrossRef
33.
Ginsberg JS, Davidson BL, Comp PC, Francis CW, Friedman RJ, Huo MH, Lieberman JR, Muntz JE, Raskob GE, Clements ML, Hantel S, Schnee JM, Caprini JA (2009) Oral thrombin inhibitor dabigatran etexilate vs North American enoxaparin regimen for prevention of venous thromboembolism after knee arthroplasty surgery. J Arthroplasty 24:1–9PubMed
34.
Botticelli Investigators, Buller H, Deitchman D, Prins M, Segers A (2008) Efficacy and safety of the oral direct factor Xa inhibitor apixaban for symptomatic deep vein thrombosis The Botticelli DVT dose-ranging study. J Thromb Haemost 6:1313–1318PubMedCrossRef
35.
The Einstein Investigators et al (2010) Oral rivaroxaban for symptomatic venous thromboembolism. N Eng J Med 363:2499–2510CrossRef
36.
Schulman S, Kearon C, Kakkar AK et al (2009) Dabigatran versus warfarin in the treatment of acute venous thromboembolism. N Engl J Med 361:2342–2352PubMedCrossRef
37.
Eikelboom JW, O’Donnell M, Yusuf S, et al (2010) Rationale and design of AVERROES: apixaban versus acetylsalicylic acid to prevent stroke in atrial fibrillation patients who have failed or are unsuitable for vitamin K antagonist treatment. Am Heart J 159(3):348–353 e1
38.
39.
Lopes RD, Alexander JH, Al-Khatib SM et al (2010) Apixaban for reduction in stroke and other ThromboemboLic events in atrial fibrillation (ARISTOTLE) trial: design and rationale. Am Heart J 159(3):331–339PubMedCrossRef
40.
Mahaffey KW FK, on belhalf of the ROCKET-AF investigators (2010) Stroke prevention using the oral direct factor Xa inhibitor rivaroxaban compared with warfarin in patients with nonvalvular atrial fibrillation (ROCKET AF). AHA Scientific Sessions 2010. 2010;Presentation 21839
41.
Connolly SJ, Esekowitz MD, Yusuf S et al (2009) Dabigatran versus warfarin in patients with atrial fibrillation. N Engl J Med 361:1139–1151PubMedCrossRef
42.
Wallentin L, Yusuf S, Ezekowitz MD et al (2010) Efficacy and safety of dabigatran compared to warfarin at different levels of international normalised ratio control for stroke prevention in atrial fibrillation: an analysis of the RE-LY trial. Lancet 376:975–983PubMedCrossRef
Metadata
Title
New oral anticoagulants
Authors
Taki Galanis
Lynda Thomson
Michael Palladino
Geno J. Merli
Publication date
01-04-2011
Publisher
Springer US
Published in
Journal of Thrombosis and Thrombolysis / Issue 3/2011
Print ISSN: 0929-5305
Electronic ISSN: 1573-742X
DOI
https://doi.org/10.1007/s11239-011-0559-8

Other articles of this Issue 3/2011

Journal of Thrombosis and Thrombolysis 3/2011 Go to the issue

OriginalPaper

Practical management approaches to anticoagulation non-compliance, health literacy, and limited English proficiency in the outpatient clinic setting

EditorialNotes

Proceedings of the 11th national conference on anticoagulant therapy

OriginalPaper

Anticoagulation in the management of venous thromboembolism in the cancer patient

OriginalPaper

Practical issues with vitamin K antagonists: elevated INRs, low time-in-therapeutic range, and warfarin failure

OriginalPaper

Quality measures and benchmarking for warfarin therapy

OriginalPaper

Evidence-based approach to thrombophilia testing
Live Webinar | 27-06-2024 | 18:00 (CEST)

Keynote webinar | Spotlight on medication adherence

Reserve your place

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

WHO estimates that half of all patients worldwide are non-adherent to their prescribed medication. The consequences of poor adherence can be catastrophic, on both the individual and population level.

Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.

Prof. Kevin Dolgin
Prof. Florian Limbourg
Prof. Anoop Chauhan
Developed by: Springer Medicine
Obesity Clinical Trial Summary

At a glance: The STEP trials

Read more

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine
Image Credits