Author + information
- Diana A. Gorog,
- Christos Christopoulos,
- Maria N. Niespialowska-Steuden,
- Robert Kozarski and
- Robert Wilcox
The propensity for thrombus formation is determined by the balance between prothrombotic factors and endogenous thrombolysis. Impaired thrombolytic status is associated with increased cardiovascular risk. Vorapaxar is a novel oral, PAR-1 antagonist that inhibits thrombin-induced platelet activation. We sought to assess the effect of vorapaxar on global thrombotic and thrombolytic status.
In the TRACER and TRA 2P-TIMI 50 studies, patients with established atherosclerosis were randomized to receive blinded vorapaxar (V) 2.5mg daily or placebo (P), in addition to standard care, after a 40-mg loading dose in TRACER. In 57 patients enrolled in a single center, blood was tested with the point-of-care Global Thrombosis Test (GTT), >2 months of stabilisation on treatment and again after discontinuation. The GTT is a fully automated test employing non-anticoagulated blood to assess thrombotic and thrombolytic status, by measuring the time required to form a shear-induced thrombus under physiological conditions, (occlusion time, OT), and in the second phase of the test, measuring the time to achieve endogenous lysis of the thrombus (lysis time, LT).
Patients on V exhibited longer OT on vs. off treatment [median 561s (25th-75th%ile: 406–656) vs. 372s (322–459), P=0.002] and shorter LT on treatment than off [1158s (727-1529) vs. 1733s (1364-2268), P=0.015]. Patients on P showed no difference in OT [419s (342-516) vs. 411s (340-540), P=0.67] or LT [1236s (977-1613) vs. 1400s (1084-1694), P=0.53] on and off treatment. During treatment, OT was longer in patients taking V, compared to P [561s (406-656) vs. 419s (342-516), P=0.009], but LT was similar in the V and P arms [1158s (727-1529) vs. 1236s (977-1613), P=0.28].
Vorapaxar prolongs OT and shortens LT, with a favorable effect on thrombotic and thrombolytic status. In addition to its antiplatelet effect, V significantly enhances thrombolytic status, which is frequently impaired in coronary disease. This action could contribute to its atherothrombotic benefits and confer additional protection in those with impaired LT.
Poster Sessions, Expo North
Monday, March 11, 2013, 9:45 a.m.-10:30 a.m.
Session Title: ACS Therapy: Basic and Translational
Abstract Category: 3. Acute Coronary Syndromes: Therapy
Presentation Number: 1301-203
- 2013 American College of Cardiology Foundation