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Emerging antiplatelet agents, differential pharmacology, and clinical utility.

ABSTRACT: The aspirin-clopidogrel combination is the current gold standard antiplatelet regimen following percutaneous coronary intervention and for the treatment of acute coronary syndrome. Despite the clinical benefit of this combination, patients continue to have vascular events. Another purinergic (P2Y(12)) receptor antagonist, prasugrel, became available last year. Although prasugrel is superior to clopidogrel in reducing clinical endpoints, a higher bleeding rate has been identified particularly in high-risk patients. Ticagrelor, a reversible P2Y(12) receptor antagonist currently being evaluated for approval, is also more potent than clopidogrel but has a similar bleeding risk. Two additional P2Y(12) antagonists are being investigated that will be available as an intravenous formulation. Apart from the P2Y(12) receptor antagonists, multiple other agents are being developed with unique mechanisms of platelet inhibition. These agents are being studied as an alternative to or in combination with clopidogrel. The antiplatelet agents currently under development include: thrombin receptor antagonists, phosphodiesterase inhibitors, a thromboxane-prostaglandin receptor antagonist, a serotonin receptor blocker, a platelet adhesion antagonist, nitric oxide-releasing aspirin, a glycoprotein VI antagonist, and a cyclooxygenase inhibitor. The purpose of this review is to describe the efficacy and safety profiles of the emerging antiplatelet agents and their role in the treatment of atherosclerotic cardiovascular diseases.

SUBMITTER: Das P

PROVIDER: S-EPMC3262324 | biostudies-other | 2010

REPOSITORIES: biostudies-other

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Emerging antiplatelet agents, differential pharmacology, and clinical utility.

Das Pranab P Oliphant Carrie S CS Beach Elizabeth E Thapa Rashmi R

Journal of blood medicine 20100531

The aspirin-clopidogrel combination is the current gold standard antiplatelet regimen following percutaneous coronary intervention and for the treatment of acute coronary syndrome. Despite the clinical benefit of this combination, patients continue to have vascular events. Another purinergic (P2Y(12)) receptor antagonist, prasugrel, became available last year. Although prasugrel is superior to clopidogrel in reducing clinical endpoints, a higher bleeding rate has been identified particularly in ...[more]

PMID: 22282687

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Project description:In patients undergoing percutaneous coronary intervention (PCI), the standard of care is dual antiplatelet therapy with a P2Y12 inhibitor (clopidogrel, prasugrel, or ticagrelor) and aspirin. Current clinical practice guidelines now recommend more potent P2Y12 inhibitors (prasugrel or ticagrelor) over clopidogrel in acute coronary syndrome (ACS). However, clopidogrel remains the most commonly prescribed P2Y12 inhibitor in the setting of PCI and is also the preferred agent in the treatment and secondary prevention of stroke. Clopidogrel is a prodrug that requires bioactivation by the CYP2C19 enzyme. It has been shown that clopidogrel use in patients who are CYP2C19 no function allele carriers are associated with impaired antiplatelet inhibition and a higher risk of major adverse cardiovascular and cerebrovascular events. Compared to clopidogrel, prasugrel and ticagrelor clinical response is not impacted by CYP2C19 genotype. Even with a demonstrated increased risk of adverse outcomes in CYP2C19 no function allele carriers treated with clopidogrel, routine implementation of CYP2C19 genotyping to guide antiplatelet therapy selection has remained controversial and has not been widely adopted. Recent results from multiple prospective randomized and nonrandomized clinical trials investigating the use of CYP2C19 genotype-guided antiplatelet therapy following PCI have advanced the evidence base demonstrating the clinical utility of this strategy. Multiple recent studies have examined the effects of CYP2C19 genotype on clopidogrel outcomes in the setting of stroke and neurointerventional procedures. In this review, we discern the clinical utility of using CYP2C19 genotype testing to guide antiplatelet therapy prescribing by evaluating the impact of CYP2C19 genotype-guided selection of antiplatelet therapy on clinical outcomes, summarizing emerging data from cardiovascular and neurology clinical studies, and discussing implications for clinical practice guidelines, remaining knowledge gaps and future research directions.

Dataset Information

Emerging antiplatelet agents, differential pharmacology, and clinical utility.

Publications

Emerging antiplatelet agents, differential pharmacology, and clinical utility.

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