Antiplatelet Therapy in Cardiovascular Disease

Copyright

Contents

List of Contributors

Foreword

Preface

Section I Platelet Biology and Pathophysiology

1 Platelet Pathophysiology and its Role in Thrombosis

Role of platelets during initiation of atherosclerosis and plaque formation

Role of platelets in thrombosis

References

2 Platelet Receptors and Drug Targets: COX-1

Structure, expression, and catalytic activity of platelet COX-1

Functional role of platelet COX -1

Genetic polymorphisms of COX-1 and COX-2 expression in platelets

Platelet COX-1 as a target for antithrombotic therapy

Interaction between aspirin and naNSAIDs at the level of platelet COX-1

In vitro and in vivo evidence for aspirin/naNSAID interaction

Concluding remarks

References

3 Platelet Receptors and Drug Targets: P2Y12

P2 receptors

Roles of adenine nucleotides in platelet function

P2Y12

Conclusions

References

4 Platelet Receptors and Drug Targets: GP IIb/IIIa

Introduction

Biology of the receptor

Glycoprotein IIb/IIIa receptor in platelet physiology

Platelet aggregation phase

“Inside-out” and “outside-in” GPIIb/IIIa signaling phenomenon

Glycoprotein IIb/IIIa receptor and thrombus formation

Glycoprotein IIb/IIIa receptor antagonists

Intravenous versus oral preparations: clinical aspects

Acknowledgment

References

5 Platelet Receptors and Drug Targets: PAR1, Collagen, vWF, Thromboxane, and Other Novel Targets

Introduction

Protease-activated receptor 1 (PAR1)

References

6 Role of Inflammation and Hypercoagulability in Thrombosis

References

Section II Platelet Function Tests

7 Light Transmission Aggregometry

Technique

References

8 Vasodilator-Stimulated Phosphoprotein (VASP) Assay

Introduction

The VASP index assay

VASP index and clinical events

Alteration of antiplatelet therapy based on the VASP index

VASP index and new oral antiplatelet agents

Conclusions

References

9 VerifyNow P2Y12 and Plateletworks Assays

Introduction

Verifynow P2Y12

Plateletworks

Validity of the test in measuring antiplatelet effect and its association with clinical outcomes

Conclusion

References

10 Multiplate Analyzer

Historical background

Principles of the Multiplate® analyzer

Advantages

Disadvantages

Clinical studies in cardiovascular medicine

Studies in cardiovascular surgery

Consensus definitions and cutoff values concerning platelet reactivity

Summary

Acknowledgment

References

11 Shear Stress-Based Platelet Function Tests

PFA-100

IMPACT-R

References

12 Thrombelastography and Other Novel Techniques

Novel techniques

T2 magnetic resonance (T2MR)

Shear-induced platelet aggregation assays

References

Section III Antiplatelet pharmacology

13 Aspirin

Mode of antiplatelet action

Time dependency of inhibition of platelet function by aspirin

Dose-dependent inhibition of platelet function by aspirin

Negative interactions with other drugs

Positive interactions with other drugs

Side effects of aspirin in antiplatelet doses

References

14 Cilostazol

Introduction

Mode of action of cilostazol

Vascular smooth muscle cells

Endothelial cells

Platelets

Heart

Brain cells

Lipid profiles

Pharmacokinetics

Conclusion

References

15 Abciximab

Abciximab in PCI: The EPIC, EPILOG, and EPISTENT trials

Abciximab in acute coronary syndromes: CAPTURE, RAPPORT, ADMIRAL, CADILLAC, and INFUSE-AMI trials

Head-to-head GPIIb/IIIa trial, noninferiority trials using abciximab versus bivalirudin, and the ISAR-REACT trials

Conclusions

References

16 Tirofiban

Introduction

Tirofiban

Dosing of tirofiban

Tirofiban in STEMI

Early administration of tirofiban: High-dose bolus regimen

Meta-analysis

References

17 Eptifibatide

Background

Dosing and efficacy

Eptifibatide use during non-ST-segment myocardial infarction

Timing of eptifibatide administration

Eptifibatide use during ST-segment myocardial infarction

Conclusions

References

18 Ticlopidine

Pharmacological properties

Pharmacodynamic profile

Genetic considerations

Clinical efficacy in patients undergoing PCI

Safety and side effects

Conclusions

References

19 Clopidogrel

Pharmacodynamic properties

Pharmacokinetic properties

Therapeutic use

References

20 Prasugrel

Introduction

Mechanism of action

Prasugrel pharmacodynamics

Clinical studies

Summary

References

21 Elinogrel

Introduction

Shortcomings of current therapy

Pharmacological principles of elinogrel

Phase I clinical studies

Phase II clinical studies

Conclusion

References

22 Cangrelor

Pharmacological properties

Preclinical studies and early phase clinical investigations

Drug interactions

Cangrelor in patients undergoing PCI: phase III studies

Cangrelor in patients undergoing surgery

Conclusion

References

23 Ticagrelor

Introduction

Mechanisms of action

Pharmacodynamics

Clinical studies

Summary

References

24 Thrombin Receptor Antagonists

Introduction

Protease-activated receptors (PARs) and thrombin-induced platelet activation

Thrombin receptor antagonists: pharmacokinetics and pharmacodynamics

Vorapaxar

Clinical trials of vorapaxar

Atopaxar

Future prospective of PAR-1 antagonists

References

Section IV Percutaneous Coronary Intervention and Antiplatelet Therapy

25 Dual Antiplatelet Therapy Prior to Percutaneous Coronary Intervention

Acetylsalicylic acid

P2Y12 receptor inhibitors

References

26 Duration of Dual Antiplatelet Therapy after Drug-Eluting Stent Implantation

Introduction

Prolonged DAPT duration greater than 12 months

Shortened DAPT duration less than 12 months

Stent-specific considerations

Patient-specific considerations

DAPT interruption

Summary

References

27 Antiplatelet Therapy for Patients with Acute Coronary Syndromes

Acetylsalicylic acid

Clopidogrel

Prasugrel

Ticagrelor

Glycoprotein IIb/IIIa inhibitors

Conclusion

References

28 Antiplatelet Therapy in Stable Coronary Artery Disease

Introduction

Aspirin

Clopidogrel

GPS IIB/IIIA

Conclusions

References

29 Antiplatelet Therapy for Patients with Peripheral Arterial Disease

Introduction

Antiplatelet therapy

Percutaneous therapy

Treatment after peripheral artery bypass graft surgery

Conclusions

References

30 Bleeding Risk and Outcomes of Patients Undergoing Percutaneous Coronary Intervention Treated with Antiplatelets

Introduction

Summary

References

31 Bleeding Definitions

Introduction

Heterogeneous bleeding definitions

The need for standardization

The Standardized BARC definition

References

Section V Antiplatelet Responsiveness

32 Personalizing Antiplatelet Therapy

Randomized trials of personalized antiplatelet therapy guided by platelet function testing

Personalized antiplatelet therapy in the surgical patient

Conclusions

References

33 Aspirin Resistance

Introduction

Definition, prevalence, and clinical implications of aspirin resistance

Potential mechanisms and targeted approaches to aspirin resistance

General management considerations

Conclusions

References

34 Clopidogrel Resistance

Evidence for a threshold of posttreatment platelet reactivity (high on-treatment platelet reactivity) associated with long-term ischemic events

Mechanisms responsible for clopidogrel nonresponsiveness

Conclusions

References

35 Genetics of Clopidogrel Poor Response

Introduction

Candidate gene approach

PON 1: Have we found the grail?

Genome-wide association studies

Perspectives and conclusion

References

36 Proton Pump Inhibitors and Clopidogrel

Introduction

Metabolism of clopidogrel and proton pump inhibitors

Pharmacodynamic studies of clopidogrel and proton pump inhibitors

Retrospective clinical studies and meta-analyses

Randomized clinical trials

Conclusion

References

37 Other Drug Interactions with Clopidogrel

Introduction

Drug metabolism

The clopidogrel–atorvastatin interaction

Other clopidogrel–drug interactions

Confounding variables in the drug interaction debate

Research challenges in the drug interaction debate

Conclusions

References

Index