Optimal use of platelet glycoprotein IIb/IIIa receptor antagonists in patients undergoing percutaneous coronary interventions.
ABSTRACT Discovery of the central role of platelets in the pathogenesis of acute coronary syndromes (ACS) and ischaemic complications of percutaneous coronary interventions (PCI) has led to the widespread use of oral and parenteral platelet inhibitors to treat these conditions. Glycoprotein (GP) IIb/IIIa (also known as α(IIb)β(3)) receptors on the surface of platelets play an essential role in platelet aggregation and serve as a key mediator in the formation of arterial thrombus. When activated, GP IIb/IIIa receptors bind to fibrinogen, which serves as the 'final common pathway' in platelet aggregation. Of the numerous agents developed for modulating platelet activity, intravenous platelet GP IIb/IIIa receptor antagonists are the most potent. There are four agents in clinical use, including abciximab, eptifibatide, tirofiban and lamifiban, although lamifiban is not approved for use in the US. While all agents block fibrinogen binding to GP IIb/IIIa, they do so by different mechanisms. Abciximab is a humanized form of a murine monoclonal antibody directed against GP IIb/IIIa, eptifibatide is a synthetic, cyclic heptapeptide that contains a lysine-glycine-aspartic acid (KGD) sequence that mimics the arginine-glycine-aspartic acid (RGD) sequence found on GP IIb/IIIa, tirofiban is a non-peptide antagonist derived by optimization of the tyrosine analogue that structurally mimicks the RGD-containing loop of the disintegrin echistatin, and lamifiban is a synthetic, non-cyclic, non-peptide, low-molecular-weight compound. In clinical trials, use of these agents reduces ischaemic adverse cardiovascular events in patients with ACS undergoing PCI, but at a cost of increased bleeding.
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ABSTRACT: Platelet adhesion and aggregation at the site of coronary stenting can have catastrophic clinical and economic consequences. Therefore, effective platelet inhibition is vital during and after percutaneous coronary intervention. Eptifibatide is an intravenous antiplatelet agent that blocks the final common pathway of platelet aggregation and thrombus formation by binding to glycoprotein IIb/IIIa receptors on the surface of platelets. In clinical studies, eptifibatide was associated with a significant reduction of mortality, myocardial infarction, or target vessel revascularization in patients with acute coronary syndrome undergoing percutaneous coronary intervention. However, recent trials conducted in the era of dual antiplatelet therapy and newer anticoagulants failed to demonstrate similar results. The previously seen favorable benefit of eptifibatide was mainly offset by the increased risk of bleeding. Current American College of Cardiology/American Heart Association guidelines recommend its use as an adjunct in high-risk patients who are undergoing percutaneous coronary intervention with traditional anticoagulants (heparin or enoxaparin), who are not otherwise at high risk of bleeding. In patients receiving bivalirudin (a newer safer anticoagulant), routine use of eptifibatide is discouraged except in select situations (eg, angiographic complications). Although older pharmacoeconomic studies favor eptifibatide, in the current era of P2Y12 inhibitors and newer safer anticoagulants, the increased costs associated with bleeding make the routine use of eptifibatide an economically nonviable option. The cost-effectiveness of eptifibatide with the use of strategies that decrease the bleeding risk (eg, transradial access) is unknown. This review provides an overview of key clinical and economic studies of eptifibatide well into the current era of potent antiplatelet agents, novel safer anticoagulants, and contemporary percutaneous coronary intervention.Therapeutics and Clinical Risk Management 08/2014; 10:603-14. DOI:10.2147/TCRM.S35664 · 1.34 Impact Factor
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ABSTRACT: Aim: Vorapaxar is a proteaseactivated receptor (PAR)-1 antagonist being developed for the prevention and treatment of thrombotic vascular events. To evaluate race/ethnic differences between Caucasians and Chinese in the pharmacokinetics of vorapaxar and its active metabolite SCH 2046273 (M20) or in the metabolite/parent ratio, we conducted a cross-study comparison on pharmacokinetic data of vorapaxar and M20 obtained from two similarly designed studies: one in healthy Chinese subjects and the other in a healthy Western (United States, [U.S.]) population. Methods: The pharmacokinetic profiles of vorapaxar and M20 were characterized using open label, two treatment parallel group designs in men and women aged 18 - 45 years. Vorapaxar was administered orally as a single dose of 40 mg in Chinese subjects (n = 14) or 120 mg in U.S. subjects (n = 14), or 2.5 mg QD for 6 weeks in both studies (Chinese, n = 14; U.S., n = 23). Results: Vorapaxar was rapidly absorbed in both Chinese and U.S. subjects. Vorapaxar and M20 had similar elimination half-lives. The range of metabolite/parent ratios after single dose or daily administration was largely overlapped in Chinese and U.S. subjects. Steady state was attained by day 21 for vorapaxar and M20 in both race/ethnic groups. The accumulation ratios for vorapaxar and M20 during daily administration were similar in Chinese and U.S. subjects. Vorapaxar was well-tolerated in Chinese and U.S. subjects. Conclusion: The pharmacokinetic profiles of vorapaxar and M20 and the metabolite/parent ratios in healthy Chinese were generally comparable to those in a healthy Western population.International journal of clinical pharmacology and therapeutics 08/2014; DOI:10.5414/CP202121 · 1.04 Impact Factor
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ABSTRACT: Thrombosis remains a significant complication of microvascular free tissue transfer. Recent discoveries in the field of vascular biology have led to a greater understanding of thrombogenesis and the pivotal role that platelets play in the formation of a clot. However, current antithrombotic strategies in the clinical practice of free tissue transfer have not typically focused on platelet inhibition. Decades of cardiovascular clinical trials have delineated the essential role of platelet inhibitor therapy in patients with acute coronary syndromes and those undergoing percutaneous coronary interventions. Understanding the current treatment guidelines for antiplatelet therapy across the spectrum of patients with coronary heart disease may provide insights into their use in the prevention and treatment of thrombosis in microvascular surgery. In this review, we examine the current antiplatelet agents in clinical use and discuss the potential role of platelet inhibition in free flap surgery, particularly in the setting of repeated microvascular thrombosis.Journal of Reconstructive Microsurgery 08/2014; 30(9). DOI:10.1055/s-0034-1381955 · 1.01 Impact Factor