Title:Vorapaxar, a Protease-Activated Receptor-1 Antagonist, a Double –Edged Sword!
Volume: 9
Issue: 2
Author(s): Bharti Bhandari and Bharati Mehta
Affiliation:
Keywords:
Anti platelet therapy, acute coronary syndrome, myocardial Infarction, PAR-1 antagonist, peripheral arterial disease,
vorapaxar.
Abstract: Acute coronary syndrome (ACS) constitutes a group of pathophysiological entities resulting
from reduced blood flow in the coronary arteries leading to decreased or improper functioning or
death of heart muscle. Such patients are usually prescribed combination antiplatelet drug therapy, containing
acetylsalicylic acid (aspirin) and an adenosine diphosphate receptor inhibitor to prevent recurrence
of ischemic events. The combination prophylactic therapy to certain extend has been successful
in preventing secondary complications including ischemic/thrombotic events in these patients. However,
research is still on for newer advances in anti-thrombotic therapy that can further prevent secondary complications of
Acute Coronary Syndrome.
Vorapaxar is a newer drug recommended along with aspirin or clopidogril for prevention of recurrence of cardiac events.
Vorapaxar, a thrombin receptor antagonist acts by reversible inhibition of the protease-activated receptor-1 (PAR-1).
PAR-1 is expressed on platelets, and it inhibits platelet aggregation, both thrombin-induced and thrombin receptor agonist
peptide (TRAP)-induced. Various trials world -wide have documented its efficacy as an anti-platelet agent for preventing
recurrent cardiovascular ischemic events but at the expense of increased bleeding complications including intracranial
haemorrhage (ICH), when compared to standard therapy alone. For the same reason, vorapaxar is contraindicated in patients
with prior stroke, transient ischemic attack and ICH.
U.S. Food and Drug Administration (FDA) approved vorapaxar in May 2014 as an antiplatelet agent along with standard
anti-platelet therapy for the reduction of recurring thrombotic cardiovascular events in patients with a history of myocardial
infarction or with peripheral arterial disease. Vorapaxar is developed and marketed by Merck Sharp Dohme and is
available by the brand name ‘Zontivity’ as 2.5 mg oral tablet equivalent to 2.08 mg of vorapaxar sulfate.. There are two
patents protecting this drug.
