Vorapaxar, a novel oral antiplatelet drug

Kranti Tekulapally

Abstract


Vorapaxor is first in the class of protease activated receptor 1 (PAR 1) antagonists. It acts by inhibiting the binding of thrombin to PAR 1 and thereby prevents platelet aggregation. USFDA approved it in May 2014 as the results of clinical trials showed that the benefit: risk ratio was high. It is to be used in a dose of 2.5 mg once daily as triple antiplatelet therapy with aspirin and clopidogrel for reduction of thrombotic cardiovascular events in patients with a history of myocardial infarction or peripheral arterial disease. Increase in the incidence of intracranial hemorrhage is the major side-effect seen.


Keywords


Vorapaxar, Protease activated receptor 1 antagonsit, Thrombin receptor antagonist

Full Text:

PDF

References


Christopher P, Braunwald E. Unstable angina and non ST segment elevation myocardial infarction. In: Longo DL, Fauci AS, Kasper DL, Hauser SL, Jameson JL, Loscalzo J, editors. Harrison’s Principles of Internal Medicine. 18th Edition. New York: McGraw Hill; 2012: 2015-21.

Olivier D, Carlos U, Martin S, Nigel W. Proteinase-activated receptors: novel mechanisms of signaling by serine proteases. Am J Physiol. 1998;274(6):1429-52.

TRA*CER Executive and Steering Committees. The Thrombin Receptor Antagonist for Clinical Event Reduction in Acute Coronary Syndrome (TRA*CER) trial: study design and rationale. Am Heart J. 2009;158(3):327-34.e4.

Kosoglou T, Reyderman L, Tiessen RG, van Vliet AA, Fales RR, Keller R, et al. Pharmacodynamics and pharmacokinetics of the novel PAR-1 antagonist vorapaxar (formerly SCH 530348) in healthy subjects. Eur J Clin Pharmacol. 2012;68(3):249-58.

Chackalamannil S, Davies RJ, Wang Y, Asberom T, Doller D, Wong J, et al. Total Synthesis of (+)-Himbacine and (+)-Himbeline. J Org Chem. 1999;64(6):1932-940.

Kosoglou T, Kraft WK, Kumar B, Statkevich P, Xuan F, Ma L, et al. Pharmacokinetics and pharmacodynamics of the novel PAR-1 antagonist vorapaxar in patients with end-stage renal disease. Eur J Clin Pharmacol. 2012;68(7):1049-56.

Statkevich P, Kosoglou T, Preston RA, Kumar B, Xuan F, Trusley C, et al. Pharmacokinetics of the novel PAR-1 antagonist vorapaxar in patients with hepatic impairment. Eur J Clin Pharmacol. 2012;68(11):1501-8.

Kosoglou T, Reyderman L, Kasserra C, Jennings LK, Young S, Xuan F, et al. No differences in the pharmacodynamics and pharmacokinetics of the thrombin receptor antagonist vorapaxar between healthy Japanese and Caucasian subjects. Eur J Clin Pharmacol. 2012;68(3):291-300.

Macaulay TE, Allen C, Ziada KM. Thrombin receptor antagonism -the potential of antiplatelet medication SCH 530348. Expert Opin Pharmacother. 2010;11(6):1015-22.

Tricoci P, Huang Z, Held C, Moliterno DJ, Armstrong PW, Van de Werf F, et al. Thrombin-receptor antagonist vorapaxar in acute coronary syndromes. N Engl J Med. 2012;366(1):20-33.

Morrow DA, Braunwald E, Bonaca MP, Ameriso SF, Dalby AJ, Fish MP, et al. Vorapaxar in the secondary prevention of atherothrombotic events. N Engl J Med. 2012;366(15):1404-13.

Kosoglou T, Statkevich P, Kumar B, Xuan F, Schiller JE, Johnson-Levonas AO, et al. The effect of multiple doses of ketoconazole or rifampin on the single- and multiple-dose pharmacokinetics of vorapaxar. J Clin Pharmacol. 2013;53(5):540-9.

Kosoglou T, Zhu Y, Xuan F, Black L, Johnson-Levonas AO, Martinho M, et al. Vorapaxar, an oral PAR-1 receptor antagonist, does not affect the pharmacokinetics and pharmacodynamics of warfarin. Eur J Clin Pharmacol. 2012;68(11):1509-16.