Clopidogrel and the Newer P2Y12 Antiplatelet Agents: Pharmacology, Clinical Uses, and Adverse Effects

Michael P. Savage, M.D. (Editor)
Thomas Jefferson University Hospital, Philadelphia, PA, US

David L. Fischman, M.D. (Editor)
Thomas Jefferson University Hospital, Philadelphia, PA, US

Mamas A. Mamas (Editor)
Institute for Primary Care and Health Sciences, Keele University, UK

Series: Cardiology Research and Clinical Developments
BISAC: MED010000

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Cardiovascular disease remains the leading cause of death in the developed world. By preventing thromboembolic events such as heart attacks and strokes, antiplatelet drugs have become a cornerstone in the treatment of cardiovascular disease. Clopidogrel is a member of the
thienopyridine family which inhibit ADP-induced platelet activation by irreversibly binding to the P2Y12 receptor. Clopidogrel is one of the most commonly used medications with over 9 million prescriptions written annually. It is utilized in the treatment of a wide variety of cardiovascular disorders including acute coronary syndromes (ACS), percutaneous coronary intervention (PCI) with stents, cerebrovascular disease, peripheral vascular disease, and structural heart interventions. Most often, clopidogrel is used in combination with low dose aspirin, providing dual antiplatelet therapy (DAPT). Newer, more potent P2Y12 inhibitors, prasugrel and ticagrelor, are now available as alternatives to clopidogrel. These newer agents have been shown to be more effective than clopidogrel in reducing ischemic events in patients with ACS. Recently a novel intravenous P2Y12 inhibitor, cangrelor, has become available for use during PCI in patients who have not been pretreated with an oral P2Y12 inhibitor.

This book examines virtually all aspects of P2Y12 inhibitors – pharmacology, clinical uses, randomized trial results, guideline recommendations, and adverse drug effects. Important fundamental issues are reviewed including comparative pharmacology of P2Y12 inhibitors, randomized trials of clopidogrel in patients with coronary artery disease, DAPT duration after PCI, and role of platelet function testing. The newer P2Y12 inhibitors (prasugrel, ticagrelor, and cangrelor) receive special focus. Use of antiplatelet therapy in specific patient populations is discussed including patients with coronary bypass graft surgery, peripheral vascular disease, cerebrovascular disease, and structural heart disease. Management of antiplatelet therapy in patients who require anticoagulation is a particularly challenging clinical setting and is the topic of a featured review. Finally, adverse drug effects and reactions are examined in a section highlighting clopidogrel resistance, clopidogrel hypersensitivity, and bleeding complications.

This book is designed to provide a comprehensive review of clopidogrel and the newer P2Y12 inhibitors. Towards that end, the authors have enlisted an internationally renowned group of experts as contributors. It is intended to be a resource for clinicians, scientists, pharmacologists, and all healthcare professionals involved in the management of cardiovascular disease.
(Imprint: Nova Medicine and Health)

Preface

Chapter 1. Comparative Pharmacology of P2Y12 Inhibitors
(Maria E. Tsoumani, PhD, Department of Pharmacy, National and Kapodistrian University of Athens, Athens, Greece)

Chapter 2. Clopidogrel in Coronary Artery Disease: A Review of the Randomized Trials
(Ryan Watson, Michael P. Savage, David L. Fischman, Department of Medicine, Division of Cardiology, Thomas Jefferson University, Philadelphia, PA, US)

Chapter 3. Optimizing DAPT Duration after PCI: From Randomized Controlled Trials to Individualized Net Clinical Benefit
(Enrico G. Ferro, MD, Usman A. Tahir, MD, Robert W. Yeh MD, Smith Center for Outcomes Research in Cardiology, Beth Israel Deaconess Medical Center, Boston, Massachusetts)

Chapter 4. Platelet Function Tests to Assess Response to P2Y12 Inhibitors and Personalised Antiplatelet Therapy in Clinical Practice
(Bartosz Olechowski, MD, Nick Curzen, PhD, Coronary Research Group, University Hospital Southampton NHS Foundation Trust, Southampton, UK, and others)

Chapter 5. P2Y12 Inhibitors in the Setting of Coronary Artery Bypass Graft Surgery
(Heerajnarain Bulluck, PhD, and Alex Sirker, PhD, Department of Cardiology, Norfolk and Norwich University Hospital, Norwich, UK, and others)

Chapter 6. The Role of Anti-Platelets and Anti-Coagulants in Peripheral Vascular Disease
(Uzair Ashraf, MD, Nureddin Almaddah, MD, Amit Nanda, MD, Rafik ElBeblawy, MD, and Rami N. Khouzam, University of Tennessee Health Science Center, Department of Medicine, Memphis, TN, US, and others)

Chapter 7. Clopidogrel in the Management of Neurovascular Disease
(Diana L. Tzeng, MD, Robin N. Dharia MD, Shaista Alam MD, Rodney D. Bell, MD, Department of Neurology, Thomas Jefferson University, Philadelphia, PA, US)

Chapter 8. Antiplatelet Therapy after Structural Heart Interventions
(Vincent Nguyen, MD, and Nicholas J. Ruggiero II, MD, Division of Cardiology, Department of Medicine, Thomas Jefferson University Hospital, Philadelphia, PA, US)

Chapter 9. Antiplatelet Therapy in Patients Receiving Anticoagulation
(Fahad Alkhalfan, MD, Mathieu Kerneis, MD, Tarek Nafee, MD, Sudarshana Datta, MD, M. Khurram Afzal, MD, C. Michael Gibson, MD, From a the Cardiovascular Division, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, US)

Chapter 10. The Role of Newer P2Y12 Inhibitors in Acute Coronary Syndromes
(Mohamed O. Mohamed and Mamas A. Mamas, DPhil, Department of Cardiology, Keele University, Keele, UK)

Chapter 11. Cangrelor: A Novel Intravenous P2Y12 Inhibitor
(Timothy Barry, MD, Sheldon Goldberg, MD, Department of Cardiology, Pennsylvania Hospital, Philadelphia, PA, US)

Chapter 12. Clopidogrel Resistance
(Udaya S Tantry, Kevin P Bliden, Eliano P Navarese, Paul A Gurbel, Platelet and Thrombosis Research, Lutherville, MD, US, and others)

Chapter 13. Management of Clopidogrel Hypersensitivity
(Alec Vishnevsky, MD, Henry Siu MD, Nicholas J. Ruggiero, MD, Paul Walinsky, MD, David L. Fischman, MD, and Michael P. Savage, MD, Division of Cardiology, Department of Medicine, Thomas Jefferson University Hospital, Philadelphia, PA, US, and others)

Chapter 14. Antiplatelet Therapy and Subsequent Bleeding: Incidence, Prediction and Its Effect on Outcomes
(Tim Kinnaird, Department of Cardiology, Cardiff, UK)

About the Editors

Index

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