In Vitro Comparison of the Novel, Dual-acting FIIa/FXa-inhibitor EP217609C101, Unfractionated Heparin, Enoxaparin, and Fondaparinux in Preventing Cardiac Catheter Thrombosis

Overview

Journal J Thromb Thrombolysis

Specialty Cardiology & Vascular Diseases

Date 2013 Jul 4

PMID 23821043

Citations 1

Authors

Anja Kaeberich

Uwe Raaz

Alexander Vogt

Lars Maedgefessel

Eric Neuhart

Chantal Krezel

Ludovic Drouget

Baerbel Hauroeder

Michael Buerke

Karl Werdan

Axel Schlitt

Affiliations

Soon will be listed here.

Abstract

Efficient and safe anticoagulation is crucial in patients requiring percutaneous coronary intervention (PCI) or extracorporeal circulation during cardiac surgery. Although new anticoagulant strategies have emerged for PCI as alternatives to the established treatment with heparins, the development of new anticoagulants with an improved efficacy/safety ratio is still necessary. Our study compared the efficacy of the novel, dual-acting, neutralizable FIIa/FXa-inhibitor EP217609C101 (EP) at 2, 1.2, 0.9, and 0.6 μg/ml to unfractionated heparin (UFH), enoxaparin, and fondaparinux in preventing cardiac catheter thrombosis under in vitro conditions. Blood drawn by venepunction from healthy male volunteers (n = 10) pretreated with 500 mg aspirin orally was treated with the anticoagulant to test and continuously circulated through a cardiac catheter for 60 min or until the catheter became blocked by thrombotic debris. Anticoagulant efficacy was assessed by thrombus weight, electron microscopic features of the developing thrombi, and laboratory parameters. Whereas UFH, enoxaparin, EP 2, and EP 1.2 μg/ml secured maximum circulation times, statistically significant premature catheter occlusions were observed for EP 0.9, EP 0.6 μg/ml, and fondaparinux. The UFH group and both high-dose concentrations of EP showed significantly lower thrombus weights than the low-dose concentrations of EP and fondaparinux, (p ≤ 0.05). On electron microscopic analysis of the thrombotic debris no differences were observed in erythrocyte deposition between UFH, enoxaparin, and all EP concentrations tested. A significant reduction in fibrin deposition was achieved by UFH and EP 2 μg/ml but no significant differences in platelet deposition were found, except for a significant reduction for EP 0.6 μg/ml. Our in vitro study showed that EP217609C101 is a promising new drug that is dose-dependently superior to classical (UFH, enoxaparin) and newer (fondaparinux) drugs in preventing heart catheter thrombosis.

Citing Articles

Uninterrupted DOACs Approach for Catheter Ablation of Atrial Fibrillation: Do DOACs Levels Matter?.

Hardy M, Douxfils J, Dincq A, Sennesael A, Xhaet O, Mullier F Front Cardiovasc Med. 2022; 9:864899.

PMID: 35425821 PMC: 9001940. DOI: 10.3389/fcvm.2022.864899.

References

Steg P, Jolly S, Mehta S, Afzal R, Xavier D, Rupprecht H . Low-dose vs standard-dose unfractionated heparin for percutaneous coronary intervention in acute coronary syndromes treated with fondaparinux: the FUTURA/OASIS-8 randomized trial. JAMA. 2010; 304(12):1339-49. DOI: 10.1001/jama.2010.1320. View

Giardino E, Haertlein B, de Garavilla L, Costanzo M, Damiano B, Andrade-Gordon P . Cooperative antithrombotic effect from the simultaneous inhibition of thrombin and factor Xa. Blood Coagul Fibrinolysis. 2009; 21(2):128-34. DOI: 10.1097/MBC.0b013e3283358100. View

Gould W, McClanahan T, Welch K, Baxi S, Saiya-Cork K, Chi L . Inhibitors of blood coagulation factors Xa and IIa synergize to reduce thrombus weight and thrombin generation in vivo and in vitro. J Thromb Haemost. 2006; 4(4):834-41. DOI: 10.1111/j.1538-7836.2006.01830.x. View

Wright R, Ettinger S, Ganiats T, Jneid H, Philippides G, Wenger N . 2011 ACCF/AHA focused update incorporated into the ACC/AHA 2007 Guidelines for the Management of Patients with Unstable Angina/Non-ST-Elevation Myocardial Infarction: a report of the American College of Cardiology Foundation/American Heart.... J Am Coll Cardiol. 2011; 57(19):e215-367. DOI: 10.1016/j.jacc.2011.02.011. View

Chesebro J, Zoldhelyi P, Badimon L, Fuster V . Role of thrombin in arterial thrombosis: implications for therapy. Thromb Haemost. 1991; 66(1):1-5. View

Stone G, White H, Ohman E, Bertrand M, Lincoff A, McLaurin B . Bivalirudin in patients with acute coronary syndromes undergoing percutaneous coronary intervention: a subgroup analysis from the Acute Catheterization and Urgent Intervention Triage strategy (ACUITY) trial. Lancet. 2007; 369(9565):907-19. DOI: 10.1016/S0140-6736(07)60450-4. View

Stone G, Witzenbichler B, Guagliumi G, Peruga J, Brodie B, Dudek D . Bivalirudin during primary PCI in acute myocardial infarction. N Engl J Med. 2008; 358(21):2218-30. DOI: 10.1056/NEJMoa0708191. View

Silber S, Albertsson P, Aviles F, Camici P, Colombo A, Hamm C . Guidelines for percutaneous coronary interventions. The Task Force for Percutaneous Coronary Interventions of the European Society of Cardiology. Eur Heart J. 2005; 26(8):804-47. DOI: 10.1093/eurheartj/ehi138. View

Warkentin T, Levine M, Hirsh J, Horsewood P, Roberts R, Gent M . Heparin-induced thrombocytopenia in patients treated with low-molecular-weight heparin or unfractionated heparin. N Engl J Med. 1995; 332(20):1330-5. DOI: 10.1056/NEJM199505183322003. View

10.

Raaz U, Buerke M, Busshardt M, Maegdefessel L, Plehn A, Hauroeder B . Efficacy of enoxaparin, certoparin and dalteparin in preventing cardiac catheter thrombosis: an in vitro approach. J Thromb Thrombolysis. 2009; 29(3):265-70. DOI: 10.1007/s11239-009-0355-x. View

11.

Raaz U, Kaeberich A, Maegdefessel L, Buerke M, Busshardt M, Schubert S . The direct thrombin inhibitor argatroban effectively prevents cardiac catheter thrombosis in vitro. Thromb Haemost. 2010; 103(4):808-14. DOI: 10.1160/TH09-07-0456. View

12.

Montalescot G, White H, Gallo R, Cohen M, Steg P, Aylward P . Enoxaparin versus unfractionated heparin in elective percutaneous coronary intervention. N Engl J Med. 2006; 355(10):1006-17. DOI: 10.1056/NEJMoa052711. View

13.

Schlitt A, Rupprecht H, Reindl I, Schubert S, Hauroeder B, Carter J . In-vitro comparison of fondaparinux, unfractionated heparin, and enoxaparin in preventing cardiac catheter-associated thrombus. Coron Artery Dis. 2008; 19(4):279-84. DOI: 10.1097/MCA.0b013e328300426b. View

14.

Yusuf S, Mehta S, Chrolavicius S, Afzal R, Pogue J, Granger C . Effects of fondaparinux on mortality and reinfarction in patients with acute ST-segment elevation myocardial infarction: the OASIS-6 randomized trial. JAMA. 2006; 295(13):1519-30. DOI: 10.1001/jama.295.13.joc60038. View

15.

Eikelboom J, Anand S, Malmberg K, Weitz J, Ginsberg J, Yusuf S . Unfractionated heparin and low-molecular-weight heparin in acute coronary syndrome without ST elevation: a meta-analysis. Lancet. 2000; 355(9219):1936-42. DOI: 10.1016/S0140-6736(00)02324-2. View

16.

Maegdefessel L, Buerke M, Schubert S, Reindl I, Michel T, Hauroeder B . Comparison of bivalirudin, enoxaparin, and unfractionated heparin in preventing cardiac catheter thrombosis. Results of an in-vitro study. Thromb Haemost. 2008; 100(4):693-8. DOI: 10.1160/th08-04-0220. View

17.

Natarajan M, Velianou J, Turpie A, Mehta S, Raco D, Goodhart D . A randomized pilot study of dalteparin versus unfractionated heparin during percutaneous coronary interventions. Am Heart J. 2005; 151(1):175. DOI: 10.1016/j.ahj.2005.06.020. View

18.

Yusuf S, Mehta S, Chrolavicius S, Afzal R, Pogue J, Granger C . Comparison of fondaparinux and enoxaparin in acute coronary syndromes. N Engl J Med. 2006; 354(14):1464-76. DOI: 10.1056/NEJMoa055443. View

19.

Wolzt M, Weltermann A, Schneider B, FASSOLT A, Lechner K, Eichler H . Studies on the neutralizing effects of protamine on unfractionated and low molecular weight heparin (Fragmin) at the site of activation of the coagulation system in man. Thromb Haemost. 1995; 73(3):439-43. View

20.

Antman E, Hand M, Armstrong P, Bates E, Green L, Halasyamani L . 2007 focused update of the ACC/AHA 2004 guidelines for the management of patients with ST-elevation myocardial infarction: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol. 2008; 51(2):210-47. DOI: 10.1016/j.jacc.2007.10.001. View