Antiplatelet Therapy in Cardiovascular Disease E-Book

• Herausgeber: John Wiley & Sons
• Kategorie: Fachliteratur
• Sprache: Englisch

Seitenzahl: 617

Veröffentlichungsjahr: 2014

Beschreibung

Edited by a team of the world’s leading interventional cardiologists and educators, this new book is created with an eye to giving the reader a solid, practical, and clinically focused understanding of this important class of drugs, from basic science to a clear-headed discussion of complex topics such as combination therapies, drug-to-drug interactions, and resistance to antiplatelet agents.

This important new book:

• Begins with a concise but thorough discussion of platelet biology and pathophysiology so that readers understand how antiplatelet agents work and why they produce such a varied range of complications, from minor GI upset to potentially life-threatening conditions such as neutropenia, a critical shortage of white blood cells.
• Thoroughly covers platelet function testing, including novel techniques.
• Clarifies current best practice regarding the use of antiplatelet agents in both chronic and acute cardiovascular disease.
• Reviews all types of antiplatelet agents – from aspirin to recently approved drugs – including indications, clinical outcomes, and side effects.

Written by an international “who’s who” of experts in the field, Antiplatelet Therapy in Cardiovascular Disease also includes an entire section covering the use of antiplatelet drugs in PCIs, including percutaneous valve repair, which makes this text particularly essential to interventional cardiologists.

Leseprobe

CONTENTS

Cover

Title page

Copyright page

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

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

P2 receptors

Roles of adenine nucleotides in platelet function

P2Y

12

Conclusions

References

4 Platelet Receptors and Drug Targets

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

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

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

Reference

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

PON1: 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

End User License Agreement

List of Tables

Chapter 04

Table 4.1 Pharmacokinetic and pharmacodynamic properties of GPIIb/IIIa antagonists.

Chapter 10

Table 10.1 Selected studies in cardiology using the Multiplate

®

analyzer

Table 10.2 Selected studies in cardiovascular surgery using the Multiplate

®

analyzer

Chapter 12

Table 12.1 Thrombelastography-derived parameters.

Chapter 16

Table 16.1 Summary of studies of tirofiban in patients with STEMI

Chapter 17

Table 17.1 Major clinical trials of eptifibatide.

Chapter 19

Table 19.1 Efficacy of CLP in major trials with reperfusion therapy.

Chapter 21

Table 21.1 Phase I clinical studies of elinogrel.

Chapter 22

Table 22.1 Efficacy and safety major end point in CHAMPION PHOENIX trial

Table 22.2 Pharmacological differences between GPIs and cangrelor as bridging strategy.

Chapter 24

Table 24.1 Phase III studies testing vorapaxar – bleeding and efficacy end points.

Chapter 25

Table 25.1 Options for dual antiplatelet therapy (DAPT) prior to percutaneous coronary intervention (PCI)

Chapter 26

Table 26.1 Randomized studies evaluating different dual antiplatelet therapy (DAPT) durations.

Chapter 28

Table 28.1 Aspirin in CSA studies.

Table 28.2 Clopidogrel in CSA studies

Chapter 29

Table 29.1 Landmark trials of antiplatelet therapy for peripheral arterial disease (PAD).

Chapter 31

Table 31.1 Definitions of Major or Severe Bleeding in Randomized Controlled Clinical Trials

Table 31.2 The Bleeding Academic Research Consortium (BARC) bleeding definition.

Chapter 34

Table 34.1 Studies linking high on-treatment platelet reactivity (HPR) to adenosine diphosphate (ADP) to ischemic events based on a receiver operating characteristic curve with a specific cutoff value.

Chapter 35

Table 35.1 Allelic frequency of common functional alleles of the CYP2C19 gene.

List of Illustrations

Chapter 01

Figure 1.1 Central role of adenosine diphosphate (ADP) P2Y

12

receptor interaction in platelet activation and aggregation during the occurrence of ischemic events and stent thrombosis. After plaque rupture, tissue factor and collagen are exposed, leading to platelet activation. Three important pathways (thrombin–protease-activated receptor-1, thromboxane [Tx] A2-thromboxane receptor, and between ADP and P2Y

12

receptor) amplify the response. The ADP–P2Y

12

interaction plays a central role. PCI indicates percutaneous coronary intervention.

Chapter 02

Figure 2.1 Interaction of oral ibuprofen with aspirin in a healthy subject, as demonstrated by arachidonic acid-induced light transmission aggregometry in two settings. (A) Aggregation before (left) and 2 h (middle) and 8 h (right) after an oral dose of 400 mg ibuprofen. Before ibuprofen,

in vitro

addition of 50 μM aspirin completely inhibits aggregation. Two hours after ibuprofen, platelets are inhibited by the high plasma concentration of ibuprofen. Eight hours after ibuprofen, the concentration of ibuprofen has fallen and aggregation has recovered. Remarkably, residual ibuprofen still interferes with the

in vitro

antiplatelet action of aspirin (see text), as shown by the failure of aspirin to prevent aggregation at this time. (B) Continuous oral administration of 100 mg/day aspirin achieves complete platelet aggregation within 4 days. Subsequent cotherapy with ibuprofen (3 × 400 mg over 4 days) abolishes inhibition by aspirin due to pharmacodynamic interaction. Four days after discontinuation of ibuprofen, platelet inhibition by aspirin is restored. Black dots mark the addition of 1 mM arachidonic acid. Actual ibuprofen plasma concentrations (HPLC) are also indicated.

Chapter 03

Figure 3.1 Simplified schematic representation of the effects of the interaction of ATP and ADP with platelet P2 receptors (P2X

1

, P2Y

1

, P2Y

12

) in platelet function. Inhibitors have been developed for each receptor, but only the P2Y

12

receptor inhibitors are shown, because they are already used in clinical practice, or are in development, as antithrombotic drugs: the AM of thienopyridines, ticagrelor, cangrelor, and elinogrel.

Figure 3.2 Central role of P2Y

12

in platelet activation and aggregation. ADP, by interacting with P2Y

12

, a seven-transmembrane receptor that is coupled to the inhibitory G protein G

i

, induces platelet aggregation and amplifies the aggregation response that is induced by other agonists (but also by ADP itself, which interacts also with its other platelet receptor, P2Y

1

, not shown in this cartoon). In addition, P2Y

12

stabilizes the platelet aggregates (not shown in this cartoon) and amplifies the secretion of platelet dense granules (δ) stimulated by secretion-inducing agonists (which are coupled to G

q

). Although P2Y

12

is coupled to inhibition of AC through G

i

, this function is not directly related to P2Y

12

-mediated platelet activation. However, it could have important implications

in vivo

, where platelets are exposed to the natural platelet antagonists, such as prostacyclin or adenosine, which inhibit platelet activation/aggregation by increasing platelet cAMP through activation of AC mediated by G

s

: inhibition of AC by P2Y

12

counteracts the inhibitory effect of these platelet antagonists, thereby favoring platelet activation and the formation of platelet aggregates

in vivo

. solid line + arrow, activation; truncated solid line, inhibition; dashed line ending with a (+), amplification; dotted line + arrow, secretion.

Chapter 04

Figure 4.1 Role of GPIIb/IIIa receptor in platelet physiology and inhibition of platelet activation–aggregation by GPIIb/IIIa antagonists. GP, glycoprotein; vWF, von Willebrand factor.

Chapter 05

Figure 5.1 Mechanisms involved in platelet activation and emerging antiplatelet drugs. Following disruption of an atherosclerotic lesion, platelets initially adhere to exposed collagen and von Willebrand factor (vWF) from the vessel wall via GPIb–V–IX on the surface under high shear force conditions. Collagen mediates firm adhesion of platelets in a two-step mechanism in which “outside-in” signaling from the collagen receptor, GPVI, and the α2β1 integrin results in the formation of a platelet monolayer. This collagen-mediated adhesion and activation of platelets leads to the release of adenosine diphosphate (ADP) and thromboxane A2 (TXA2) production via COX-1, matrix metalloprotease-1 (MMP1) activation, and thrombin generation on the surface of activated platelets. These autocrine mediators recruit additional platelets through the major fibrinogen receptor GPIIb–IIIa and activate nearby platelets to cause platelet aggregation via G protein-coupled receptors (GPCRs), PAR1, PAR4, TP, and P2Y12.

Chapter 06

Figure 6.1 Relation between platelet function, coagulation, inflammation, and disease state. Results from the Thrombosis RIsk Progression (TRIP) Study. AS, asymptomatic CAD patients; MFI, mean fluorescence intensity; SA, stable angina; UA, unstable angina. (

Platelets

, 2010,

21

, 360–367. © Informa.)

Chapter 07

Figure 7.1 A typical aggregation curve in a patient receiving chronic 75 mg/day clopidogrel therapy.

Chapter 09

Figure 9.1 VerifyNow test device. The patient sample is whole blood, which is automatically dispensed from the citrated blood collection tube. The assay device contains a lyophilized preparation of human fibrinogen-coated beads and platelet activators in its mixing chambers, which in the case of the P2Y12 test, are ADP and PGE1. The rate and extent of agglutination of the fibrinogen-coated beads is measured through changes in light transmission, and a value is reported in P2Y12 reaction units (PRU).

Figure 9.2 Distribution of VerifyNow P2Y12 PRU in several studies of clopidogrel-treated patients undergoing PCI. In the total pooled cohort of 3058 patients, the mean reactivity was 197 ± 85 PRU, and the median reactivity was 200 PRU (interquartile range, 200 PRU).

Figure 9.3 Correlation between the results of the VerifyNow P2Y12 test and light transmission aggregometry (LTA) among patients undergoing elective PCI. (A) Peak aggregation and (B) late aggregation using 20 µmol ADP. The high

y

intercept with peak aggregation is likely due to the addition of prostaglandin E1 (PGE1) in the VerifyNow P2Y12 test, which suppresses the additional contribution of ADP-induced activation of the P2Y1 pathway, resulting in a relatively higher magnitude of platelet reactivity with LTA. White dots, patients receiving clopidogrel 75 mg daily; gray dots, patients receiving clopidogrel 300 mg loading dose; black dots, patients receiving 600 mg loading dose.

Figure 9.4 Correlation between the results of VerifyNow P2Y12 and vasophosphoprotein phosphorylation analysis (VASP) in aspirin-treated patients with coronary artery disease randomly assigned to clopidogrel or prasugrel, after (A) loading dose and (B) maintenance dosing (MD). LD, loading dose; MD, maintenance dose; PRI, platelet reactivity index; PRU, P2Y12 reaction units.

Figure 9.5 Correlation between VerifyNow P2Y12 test results and concentrations of clopidogrel or prasugrel active metabolites after (A) loading dose and (B) maintenance dosing. AUC, area under the curve; LD, loading dose; MD, maintenance dose; PRU, P2Y12 reaction units; VN, VerifyNow.

Figure 9.6 Relationship between PRU and outcomes in a time-dependent analysis of the GRAVITAS trial. After adjustment for other predictors of cardiovascular events, patients who achieved a PRU less than 208 had a significantly lower risk of cardiovascular events at 60-day follow-up. ACS, acute coronary syndrome; CABG, coronary artery bypass grafting; CrCl, creatinine clearance; MI, myocardial infarction; PCI, percutaneous coronary intervention; PRU, P2Y12 reaction units.

Figure 9.7 Methodological principle of the Plateletworks assay.

Figure 9.8 Magnitude of calculated platelet (micro)aggregation according to the Plateletworks assay at different time points after the drawing of blood in the ADP tube. (A) Patients receiving dual antiplatelet therapy with aspirin and clopidogrel and (B) healthy volunteers not on antiplatelet therapy. Delay in running the test after sample collection resulted in the underestimation of platelet aggregation and overestimation of the degree of platelet inhibition, likely due to disaggregation of the formed aggregates.

Chapter 10

Figure 10.1 The Multiplate analyzer. The figure shows the components and principles of the electrical impedance aggregometer Multiplate

®

analyzer. (A) shows a Multiplate

®

test cell with two independent sensor units consisting of two pairs of electrodes, (B) shows the whole Multiplate

®

benchtop device, (C) shows the output of the device for platelet aggregation measurements that are plotted against time (in AU*min), and (D) shows an example of platelets clotting on the metal surface of the two electrodes of one sensor unit. By doing so, electrical impedance is rising between the two electrodes, and less current is flowing between the electrodes (arrows).

Figure 10.2 Electron microscopic imaging of a disposable Multiplate

®

analyzer test. Electron microscopic imaging (2000× magnified) of a disposable Multiplate

®

analyzer test cell showing platelets sticking on the surface of the electrode after a standard test.

Chapter 11

Figure 11.1 Schematic presentation of the PFA-100 system. The time needed to form a platelet plug occluding the aperture cut into a collagen/epinephrine (COL/EPI) or collagen/ADP (COL/ADP)-coated membrane is determined and reported as closure time (CT) in seconds.

Figure 11.2 Working mechanism of the IMPACT-R device. Testing a normal blood sample with the IMPACT-R results in aggregates formation on the well surface (normal SC: upper part). However, pre-incubating the blood sample under gentle mixing (10 rpm) for 1 min with an appropriate platelet agonist (e.g.: ADP, AA) induces microaggregates formation when platelets are insufficiently inhibited by clopidogrel and/or aspirin. These activated platelets lose their adhesion properties temporary until spontaneous disaggregation occurs.

Chapter 12

Figure 12.1 Schematic of thrombelastograph system: a torsion wire suspending a pin that is immersed in blood. As the clot forms while the cup is rotated 45°, the pin will rotate depending on the strength of the platelet–fibrin bonds. Signal is discharged continuously that reflects the onset of clotting (reaction time [

R

]) and the clot strength (MA).

Chapter 13

Figure 13.1 Time-dependent inhibition of thromboxane (TXB

2

) formation by aspirin, depending on dose (mg) and route of administration. Data were obtained from 21 healthy subjects treated in a crossover design. Note that both axes are in logarithmic scale.

Chapter 14

Figure 14.1 Chemical structure of cilostazol.

Figure 14.2 Mechanism of intracellular cAMP control by adenosine and PDE in platelets, vascular smooth muscle cells, and cardiomyocytes. The cAMP levels are controlled by degradation via PDE and by biosynthesis via adenylate cyclase (AC). AC activity in turn is controlled by stimulatory (Gs) and inhibitory (Gi) G-proteins. Adenosine, derived from either cellular metabolism or extracellular sources, activates Gs via A2 receptors and Gi via A1 receptors. This results in either amplification or inhibition of AC.

Figure 14.3 Action mechanism of cilostazol in platelets. When the action of PDE 3 in platelets is inhibited by cilostazol, there is an increase in the cAMP levels, which facilitates an influx of free calcium ions back into the storage granules in the platelets. ADP, adenosine diphosphate; ATP, adenosine triphosphate; cAMP, cyclic adenosine monophosphate; PDE 3, phosphodiesterase 3; PG, prostaglandin; PGG2, prostaglandin G2; PGH2, prostaglandin H2.

Chapter 16

Figure 16.1 Myocardial reperfusion data for electrocardiography, according to treatment group. The percentages of patients are shown according to the degree of residual ST-segment deviation (A) or ST-segment resolution (B) on the electrocardiogram between 30 and 90 min after angiography or percutaneous coronary intervention (PCI).

Figure 16.2 Risk ratios of angiographic outcomes, as measured by quantitative coronary angiography analysis, in early versus late presenters. LTB 5 large thrombus burden. cTFC 5 corrected TIMI frame count.

Figure 16.3 Kinetics of platelet inhibition over time after 20 µmol/L adenosine diphosphate (ADP) %IPA in patients treated with both tirofiban bolus with and without infusion versus prasugrel group alone. *

p

 = 0.05 versus %IPA measured in the prasugrel alone group at

post hoc

analysis.

Chapter 18

Figure 18.1 Ticlopidine metabolism. CYP, cytochrome P450.

Figure 18.2 Rate of major adverse cardiac events (MACE) in the studies comparing ticlopidine plus aspirin to anticoagulant therapy plus aspirin. AC, anticoagulant therapy.

Chapter 20

Figure 20.1 Prasugrel and clopidogrel metabolism.

Chapter 21

Figure 21.1 Kaplan–Meier curves of time to first bleeding event with adjudicated TIMI major, TIMI minor, and TIMI bleeding requiring medical attention (BRMA) (A) from treatment to day 120 or (B) from landmark analysis at 24 h or discharge (whichever occurred first) to 120 days

Chapter 22

Figure 22.1 Study designs of the CHAMPION trials [30, 31, 33]. (A) CHAMPION-PCI. (B) CHAMPION-PLATFORM. (C) CHAMPION PHOENIX. NSTE-ACS, non-ST-segment elevation acute coronary syndrome; PCI, percutaneous coronary intervention; SA, stable angina; STEMI, ST-segment elevation myocardial infarction; *, at the discretion of the physician.

Figure 22.2 Primary efficacy and safety end point of the BRIDGE trial. (A) Percent of patients with PRU lower than 240 for all on-treatment samples. (B) Excessive CABG surgery-related bleeding [36].

Chapter 31

Figure 31.1 Constructing a bleeding definition from three principal components.

Chapter 32

Figure 32.1 The sigmoid cumulative frequency curve in patients with post-percutaneous coronary intervention (PCI) ischemic/thrombotic clinical events relative to platelet reactivity to adenosine diphosphate (ADP). These data support the concept of a therapeutic window for P2Y

12

blockade.

Chapter 34

Figure 34.1 Various factors influencing platelet reactivity and clinical outcome during clopidogrel therapy. BMI, body mass index; CAD, coronary artery disease; CCB, calcium channel blocker; DDI, drug–drug interactions; HPR, high platelet reactivity; LPR, low platelet reactivity; PPIs, proton pump inhibitors; SJW, St. John’s wort; SNP, single nucleotide polymorphism.

Chapter 35

Figure 35.1 Clopidogrel responsiveness as assessed with the VASP assay according to the CYP2C19*1/*2 genotype in 538 clopidogrel-treated patients.

Chapter 37

Figure 37.1 Clopidogrel–drug interactions

Guide

Cover

Table of Contents

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Antiplatelet Therapy in Cardiovascular Disease

Edited by

Ron Waksman, MD, FACC

Associate Chief of Cardiology

Director of Cardiovascular Research and Advanced Education

MedStar Heart Institute at MedStar Washington Hospital Center

Washington, DC, USA

Paul A. Gurbel, MD, FACC, FAHA

Director, Sinai Center for Thrombosis Research

Associate Chief for Research

Department of Medicine

Sinai Hospital of Baltimore;

Professor of Medicine

Johns Hopkins University School of Medicine

Baltimore, MD;

Adjunct Professor of Medicine

Duke University School of Medicine

Durham, NC, USA

Michael A. Gaglia, Jr., MD, MSc

Assistant Professor of Medicine

Division of Cardiovascular Medicine

University of Southern California Keck School of Medicine

Los Angeles, CA, USA

This edition first published 2014 © 2014 by John Wiley & Sons, Ltd

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List of Contributors

Yousif Ahmad, BMedSci, BMBS, MRCPCardiology SpR and Honorary Research FellowNational Heart and Lung InstituteImperial College LondonLondon;University of Birmingham Centre for Cardiovascular SciencesCity HospitalBirmingham, UK