P2Y12 inhibitors in cardiovascular disease: focus on prasugrel.
OBJECTIVE
To review the literature describing the pharmacology, pharmacokinetic properties, efficacy, and adverse effects of prasugrel, a new thienopyridine.


METHODS
A literature search was conducted (1966-November 2008) of the MEDLINE, Current Contents, EMBASE, and International Pharmaceutical Abstract databases using the key words prasugrel, CS-747, LY640315, and P2Y(12). Bibliographies of identified literature were also reviewed for additional references.


METHODS
All reports published in English that evaluated prasugrel (or its chemical synonyms) were reviewed. Abstracts without subsequently published reports were excluded.


RESULTS
Given the high rate of recurrent coronary events despite current antiplatelet therapies, agents with potentially greater efficacy are under investigation. Prasugrel is a novel thienopyridine prodrug that is rapidly metabolized to its active platelet-inhibitory metabolite (R-138727) and exerts antiplatelet activity through antagonism of P2Y(12) receptors. Prasugrel is very similar in structure and mechanism of action to clopidogrel, as they both possess a methoxycarbonyl group that provides increased pharmacologic activity and an improved hematologic safety profile when compared with ticlopidine. In addition, when compared with clopidogrel, prasugrel demonstrates greater potency and less interpatient variability in the inhibition of platelet aggregation, less in vitro hyporesponsiveness, and, in patients with acute coronary syndromes, a reduced rate of ischemic events. However, this reduction in ischemic events was accompanied by an increased risk of major and fatal bleeding.


CONCLUSIONS
Prasugrel appears to be a promising antiplatelet agent, with emerging clinical data in direct comparison with clopidogrel supporting its role in reducing recurrent ischemic events. Further studies are needed to evaluate the safety and efficacy of prasugrel across various patient populations and clinical scenarios.
Scott
Day Marice
DM
Lloyd L Gregory School of Pharmacy, Palm Beach Atlantic University, West Palm Beach, FL 33416, USA. day_scott@pba.edu
Norwood
Rhonda M
RM
Parra
David
D
D000818:Animals; D002318:Cardiovascular Diseases / Q000188:drug therapy* / Q000378:metabolism; D002986:Clinical Trials as Topic / Q000379:methods; D006801:Humans; D010879:Piperazines / Q000009:adverse effects / Q000494:pharmacology* / Q000627:therapeutic use*; D010975:Platelet Aggregation Inhibitors / Q000009:adverse effects / Q000494:pharmacology* / Q000627:therapeutic use*; D000068799:Prasugrel Hydrochloride; D058919:Purinergic P2 Receptor Antagonists; D018048:Receptors, Purinergic P2 / Q000378:metabolism; D058925:Receptors, Purinergic P2Y12; D013876:Thiophenes / Q000009:adverse effects / Q000494:pharmacology* / Q000627:therapeutic use*
C548576:P2RY12 protein, human; D010879:Piperazines; D010975:Platelet Aggregation Inhibitors; D058919:Purinergic P2 Receptor Antagonists; D018048:Receptors, Purinergic P2; D058925:Receptors, Purinergic P2Y12; D013876:Thiophenes; D000068799:Prasugrel Hydrochloride