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Pharmacological Inhibition of Platelet Reactivity. Clinical and Pharmacodynamic Effects

[ Vol. 11 , Issue. 4 ]

Author(s):

Juana Valles, Antonio Moscardo, Isabel Madrid and Maria Teresa Santos   Pages 431 - 447 ( 17 )

Abstract:


Platelets play an important role in both normal hemostasis and pathological thrombus formation. The key role of platelets in thrombosis is highlighted by the clinical benefit of treatment with antiplatelet drugs. Aspirin, either alone or in combination with clopidogrel in high-risk patients, is the most widely used antiplatelet agent. However, there is an individual response to these agents that may reduce the cardiovascular protection in patients who achieve a lower antiplatelet effect. Recently, P2Y12 receptor antagonists more potent than clopidogrel (e.g., prasugrel and ticagrelor) have been approved for patients with acute coronary syndromes and those undergoing percutaneous coronary interventions; these drugs provide greater platelet inhibition than clopidogrel. However, the increased effectiveness of these treatments has underscored the importance of carefully balancing the risks of ischemia and bleeding to achieve the best clinical outcomes. The increased knowledge of the molecular mechanisms of platelet activation has prompted a search for novel pharmacological targets for the inhibition of platelet reactivity. This article reviews the molecular mechanisms of action and limitations of use of current and emerging antiplatelet agents for treatment of cardiovascular disease.

Keywords:

Aspirin resistance, clopidogrel, GPIIbIIIa antagonists, PAR-1 antagonists, phosphodiesterase inhibitors, prasugrel, thromboxane receptor antagonists, ticagrelor.

Affiliation:

Reseach Center University Hospital La Fe, Avda. Campanar, 21, 46009 Valencia, Spain.



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