Administration of eptifibatide to acute coronary syndrome patients receiving enoxaparin or unfractionated heparin

Lev, Eli I.; Hasdai, David; Scapa, Erez; Tobar, Ana; Assali, Abid; Lahav, Judith; Battler, Alexander; Badimón, Juan J.; Kornowski, Ran

doi:10.1016/j.jacc.2003.09.060

Cited by 15 publications

(12 citation statements)

References 37 publications

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“…Thrombus formation was obliterated with UFH ≥ 1.0 U mL −1 under both flow and static conditions. These data are in agreement with ex vivo whole blood perfusion over the porcine tunica media (Badimon chamber) at shear rate 212 s −1 or 1690 s −1 [16]. Both enoxaparin (anti‐Xa, 0.85 IU mL −1 ) and UFH (anti‐Xa, 0.57 IU mL −1 ) exert less antithrombotic effects at 1690 s −1 relative to 212 s −1 .…”

Section: Discussionsupporting

confidence: 81%

A novel automated microchip flow‐chamber system to quantitatively evaluate thrombus formation and antithrombotic agents under blood flow conditions

Hosokawa

Ohnishi

Kondo

et al. 2011

Journal of Thrombosis and Haemostasis

140

161

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To cite this article: Hosokawa K, Ohnishi T, Kondo T, Fukasawa M, Koide T, Maruyama I, Tanaka KA. A novel automated microchip flow-chamber system to quantitatively evaluate thrombus formation and antithrombotic agents under blood flow conditions. J Thromb Haemost 2011; 9: 2029-37. Summary. Background and aims:In the present study, we describe a newly developed microchip-based analytical system to evaluate white thrombus formation (WTF). Efficacies of various antithrombotic agents were compared under different flow conditions. Methods: Whole blood containing corn trypsin inhibitor was perfused over a microchip coated with collagen and tissue thromboplastin at the lower and higher shear rates of 240 and 600 s , and WTF process inside the microchip was quantified by monitoring a flow pressure. Parameters of T 10 (time to 10 kPa), T 10-80 (time from 10 to 80 kPa) and OT (occlusion time; time to 80 kPa) were used to evaluate the onset and the growth rate of WTF, and the capillary occlusion, respectively. Results: After perfusion was started, white thrombus composed of activated platelets and fibrin was formed on the coated surface. Thrombus gradually increased in size and eventually occluded the capillary. Among anticoagulants, heparin (0.5-1.0 U mL )1 ) potently prolonged T 10 at both shear rates, whereas low molecular weight heparin (1.0-2.0 IU mL )1 ) inhibited the growth of WTF at the lower shear rate. Among antiplatelet agents, abciximab (1-2 lg mL )1 ) significantly reduced the size and number of thrombi, which was additively enhanced in the presence of heparin (0.5 U mL )1). OS-1 (specific GPIba-antagonist) prevented the complete capillary occlusion. Conclusion: The novel monitoring system of WTF may be useful in preclinical and clinical evaluations of different types of antithrombotic strategies, and their effects in combination.

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Section: Discussionsupporting

confidence: 81%

A novel automated microchip flow‐chamber system to quantitatively evaluate thrombus formation and antithrombotic agents under blood flow conditions

Hosokawa

Ohnishi

Kondo

et al. 2011

Journal of Thrombosis and Haemostasis

140

161

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“…Thrombus formation under flow was evaluated using the T-TAS (Fujimori Kogyo, Kanagawa, Japan) as previously described [11]. The T-TAS system is equipped with a rectangular capillary (width, 300 µm; depth, 80 µm; length 15 mm), a pneumatic pump, and a flow pressure sensor ( Fig.…”

Section: Methodsmentioning

confidence: 99%

“…It is, therefore, clinically important to individually assess residual hemostatic functions by testing anticoagulant and antiplatelet agents under the same conditions. However, this is not feasible using conventional platelet function assays and coagulation tests [11]. Some of the latter limitations may be overcome by evaluating fibrin-rich platelet thrombus formation under flow conditions [12].…”

Section: Introductionmentioning

confidence: 99%

Comparative Evaluation of Direct Thrombin and Factor Xa Inhibitors with Antiplatelet Agents under Flow and Static Conditions: An In Vitro Flow Chamber Model

et al. 2014

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Dabigatran and rivaroxaban are novel oral anticoagulants that specifically inhibit thrombin and factor Xa, respectively. The aim of this study is to elucidate antithrombotic properties of these anticoagulant agents under arterial and venous shear conditions. Whole blood samples treated with dabigatran or rivaroxaban at 250, 500, and 1000 nM, with/without aspirin and AR-C66096, a P2Y12 antagonist, were perfused over a microchip coated with collagen and tissue thromboplastin at shear rates of 240 and 600 s−1. Fibrin-rich platelet thrombus formation was quantified by monitoring flow pressure changes. Dabigatran at higher concentrations (500 and 1000 nM) potently inhibited thrombus formation at both shear rates, whereas 1000 nM of rivaroxaban delayed, but did not completely inhibit, thrombus formation. Dual antiplatelet agents weakly suppressed thrombus formation at both shear rates, but intensified the anticoagulant effects of dabigatran and rivaroxaban. The anticoagulant effects of dabigatran and rivaroxaban were also evaluated under static conditions using thrombin generation (TG) assay. In platelet-poor plasma, dabigatran at 250 and 500 nM efficiently prolonged the lag time (LT) and moderately reduce peak height (PH) of TG, whereas rivaroxaban at 250 nM efficiently prolonged LT and reduced PH of TG. In platelet-rich plasma, however, both anticoagulants efficiently delayed LT and reduced PH of TG. Our results suggest that dabigatran and rivaroxaban may exert distinct antithrombotic effects under flow conditions, particularly in combination with dual antiplatelet therapy.

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“…20 No difference was found in the antiplatelet activity in patients with ACS undergoing coronary angiography when eptifibatide was used either with enoxaparin or unfractionated heparin. 21 The inhibition of thrombus formation was significantly greater when eptifibatide was coadministered with enoxaparin sodium than with unfractionated heparin [reduction of 75.6% versus 63.9% (P = 0.01)].…”

Section: Eptifibatide In Combination With Other Medicationsmentioning

confidence: 96%

Eptifibatide: The evidence for its role in the management of acute coronary syndromes

Shah

Khan²,

Malhotra³

et al. 2009

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Acute coronary syndromes and non-Q-wave myocardial infarction are often initiated by platelet activation. Eptifibatide is a cyclic heptapeptide and is the third inhibitor of glycoprotein (Gp) IIb/IIIa that has found broad acceptance after the specific antibody abciximab and the nonpeptide tirofiban entered the global market. Gp IIb/IIIa inhibitors act by inhibiting the final common pathway of platelet aggregation, and play an important role in the management of acute coronary syndromes. Aims: This review assesses the evidence for therapeutic value of eptifibatide as a Gp IIb/IIIa inhibitor in patients with acute coronary syndromes. Evidence review: Several large, randomized controlled trials show that eptifibatide as adjunctive therapy to standard care in patients with non-ST segment elevation acute coronary syndrome is associated with a significant reduction in the incidence of death or myocardial infarction. Data are limited regarding the use of eptifibatide in patients with ST segment elevation myocardial infarction. Cost-effectiveness analysis indicates that eptifibatide is associated with a favorable cost-effectiveness ratio relative to standard care. According to US cost-effectiveness analysis about 70% of the acquisition costs of eptifibatide are offset by the reduced medical resource consumption during the first year. Eptifibatide was well tolerated in most of the trials. Bleeding is the most commonly reported adverse event, with most major bleeding episodes occurring at the vascular access site. Major intracranial bleeds, stroke, or profound thrombocytopenia rarely occurred during eptifibatide treatment. Place in therapy: Eptifibatide has gained widespread acceptance as an adjunct to standard anticoagulation therapy in patients with acute coronary syndromes, and may be particularly useful in the management of patients with elevated troponin or undergoing percutaneous coronary interventions.

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Administration of eptifibatide to acute coronary syndrome patients receiving enoxaparin or unfractionated heparin

Abstract: The combination of eptifibatide with enoxaparin appears to have a more potent antithrombotic effect than that of eptifibatide and UFH in the doses tested.

Cited by 15 publications

References 37 publications

A novel automated microchip flow‐chamber system to quantitatively evaluate thrombus formation and antithrombotic agents under blood flow conditions

A novel automated microchip flow‐chamber system to quantitatively evaluate thrombus formation and antithrombotic agents under blood flow conditions

Comparative Evaluation of Direct Thrombin and Factor Xa Inhibitors with Antiplatelet Agents under Flow and Static Conditions: An In Vitro Flow Chamber Model

Eptifibatide: The evidence for its role in the management of acute coronary syndromes

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