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PAR-1 antagonist vorapaxar favorably improves global thrombotic status in patients with coronary disease

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Abstract

To assess the effect of vorapaxar on global thrombotic and thrombolytic status. The propensity for thrombus formation is determined by the balance between prothrombotic factors and endogenous thrombolysis. Impaired thrombolytic status increases cardiovascular risk. Vorapaxar is a novel, oral, protease-activated receptor-1 antagonist that inhibits thrombin-induced platelet activation. In the TRACER and TRA 2°P-TIMI 50 studies, patients with acute coronary syndromes and established atherosclerosis were randomized to vorapaxar 2.5 mg daily or placebo, in addition to standard care. In 57 patients enrolled in a single center, blood was tested with the point-of-care global thrombosis test, on and off treatment. This automated test employs non-anticoagulated blood to assess thrombotic and thrombolytic status, measuring the time required to form a shear-induced thrombus under physiological conditions (occlusion time, OT), and subsequently, the time to achieve endogenous lysis of the thrombus (lysis time, LT). Patients on vorapaxar exhibited longer OT on vs. off treatment [median 561 s (interquartile range 422–654) vs. 372 s(338–454), P = 0.003] and shorter LT on treatment than off [1,158 s(746–1,492) vs. 1,733 s(1,388–2,230), P = 0.016]. Patients on placebo showed no difference in OT [419 s(343–514) vs. 411 s(346–535), P = 0.658] or LT [1,236 s(985–1,594) vs. 1,400 s(1,092–1,686), P = 0.524] on and off treatment. During treatment, OT was longer in patients taking vorapaxar [561 s(422–654) vs. 419 s(343–514), P = 0.009], but LT was similar in vorapaxar and placebo arms [1,158 s(746–1,492) vs. 1,236 s(985–1,594), P = 0.277]. Vorapaxar prolongs OT and shortens LT, with favorable effects on thrombotic and thrombolytic status. In addition to its antiplatelet effect, vorapaxar may enhance endogenous thrombolysis, which is frequently impaired in coronary disease.

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Abbreviations

GTT:

Global thrombosis test

LT:

Lysis time

OT:

Occlusion time

PAR:

Protease-activated receptor

PFT:

Platelet function tests

TAFI:

Thrombin activatable fibrinolysis inhibitor

TRACER:

Thrombin-receptor antagonist vorapaxar in acute coronary Syndromes

TRA 2°P-TIMI 50:

Thrombin receptor antagonist in secondary prevention of Atherothrombotic Ischemic Events (TRA 2°P-TIMI 50)–Thrombolysis in Myocardial Infarction (TIMI) 50 trial

TRAP:

Thrombin receptor activating peptide

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Authors and Affiliations

  1. Imperial College, London, UK

    G. Rosser, M. N. Niespialowska-Steuden & D. A. Gorog

  2. East & North Hertfordshire NHS Trust, Stevenage, UK

    G. Rosser, C. Christopoulos, M. N. Niespialowska-Steuden & D. A. Gorog

  3. Duke Clinical Research Institute, Durham, NC, USA

    P. Tricoci

  4. TIMI Study Group, Cardiovascular Division, Brigham and Women’s Hospital, Boston, MA, USA

    D. Morrow

  5. University of Hertfordshire, Hertfordshire, UK

    C. Christopoulos, R. Kozarski & D. A. Gorog

  6. University of Nottingham, Nottingham, UK

    R. Wilcox

Authors
  1. G. Rosser
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  2. P. Tricoci
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  3. D. Morrow
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  4. C. Christopoulos
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  5. M. N. Niespialowska-Steuden
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  6. R. Kozarski
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  7. R. Wilcox
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  8. D. A. Gorog
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Correspondence to D. A. Gorog.

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Rosser, G., Tricoci, P., Morrow, D. et al. PAR-1 antagonist vorapaxar favorably improves global thrombotic status in patients with coronary disease. J Thromb Thrombolysis 38, 423–429 (2014). https://doi.org/10.1007/s11239-014-1075-4

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  • DOI: https://doi.org/10.1007/s11239-014-1075-4

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