Pharmacological inhibition of platelet reactivity. Clinical and pharmacodynamic effects

Curr Vasc Pharmacol. 2013 Jul;11(4):431-47. doi: 10.2174/1570161111311040007.

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Blood Platelets / drug effects*
  • Blood Platelets / metabolism
  • Cardiovascular Diseases / drug therapy*
  • Cardiovascular Diseases / physiopathology
  • Drug Approval
  • Drug Design
  • Hemostasis
  • Humans
  • Molecular Targeted Therapy
  • Platelet Activation / drug effects
  • Platelet Aggregation Inhibitors / adverse effects
  • Platelet Aggregation Inhibitors / pharmacology*
  • Platelet Aggregation Inhibitors / therapeutic use
  • Purinergic P2 Receptor Antagonists / adverse effects
  • Purinergic P2 Receptor Antagonists / pharmacology
  • Purinergic P2 Receptor Antagonists / therapeutic use
  • Thrombosis / drug therapy
  • Thrombosis / pathology

Substances

  • Platelet Aggregation Inhibitors
  • Purinergic P2 Receptor Antagonists