Effects of escalating doses of tirofiban on platelet aggregation and major receptor expression in diabetic patients: Hitting the TARGET in the TENACITY trial?

Victor Serebruany, Alex Malinin, Alex Pokov, Umesh Arora, Dan Atar, Dominick Angiolillo

Research output: Contribution to journalArticle

Abstract

Introduction: Ongoing search for the optimal dosing regimens, and valid concerns that some GPIIb/IIIa inhibitors may cause rebound platelet activation are limiting the use of these agents in patients with acute vascular events. Materials and methods: We assessed the in vitro effects of preincubation with escalating (12.5-200 ng/mL) concentrations of tirofiban on platelet biomarkers in 20 diabetic patients. Platelet activity was assessed by ADP-, and collagen-induced conventional plasma aggregometry, and by whole blood flow cytometry measuring expression of PECAM-1, GPIb, GP IIb/IIIa antigen and activity, vitronectin, P-selectin, LAMP-1, GP 37, LAMP-3, activated and intact PAR-1 thrombin receptors, GPIV, and platelet-monocyte formation. All patients were treated with aspirin (at least 81 mg daily for 1 month); other antiplatelet agents were not allowed. Results: Significant decrease of ADP-induced platelet aggregation was observed starting at the low 12.5 ng/mL concentration (p = 0.0001), with total inhibition occurring at 50 ng/mL of tirofiban dose. Inhibition of collagen-induced platelet aggregability requires 25 ng/ml of tirofiban (p = 0.002), and was complete at 100 ng/mL. Dose-dependent blockade of GP IIb/IIIa activity was observed with tirofiban concentrations over 50 ng/mL (p = 0.003). Other receptors were unaffected even with the high doses of tirofiban (100-200 ng/mL). Conclusion: Tirofiban completely inhibits ADP- and, with the higher dose, collagen-induced platelet aggregation. Higher loading dose of tirofiban used in the ongoing TENACITY trial (100 ng/mL) may be superior with regard to clinical outcomes to the regimens used in PRISM-PLUS (25 ng/mL), or TARGET (50 ng/mL). Selective inhibition of GPIIb/IIIa activity, and lack of alternative platelet activation beyond the GP IIb/IIIa blockade may represent the therapeutic advantage of tirofiban over other agents.

Original languageEnglish (US)
Pages (from-to)175-181
Number of pages7
JournalThrombosis Research
Volume119
Issue number2
DOIs
StatePublished - 2007

Keywords

  • Acute coronary syndrome
  • Diabetes
  • In vitro
  • Platelets
  • Tirofiban

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Hematology

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