Clinical, Interventional and Investigational Thrombocardiology (Fundamental and Clinical Cardiology)

Front cover......Page 1
Series Introduction......Page 8
Foreword......Page 10
Preface......Page 12
Contents......Page 14
Contributors......Page 22
I. INTRODUCTION......Page 28
II. INTRINSIC AND EXTRINSIC PATHWAYS TO THROMBIN GENERATION......Page 31
III. INITIATION......Page 32
V. TERMINATION......Page 35
VI. ELIMINATION/FIBRINOLYSIS......Page 36
VII. MODELS OF THROMBIN GENERATION......Page 39
VIII. INITIATION OF COAGULATION......Page 40
IX. CLOT FORMATION......Page 41
XI. TERMINATION......Page 45
XII. PHENOTYPIC PROFILES OF THE INITIATION, CLOT FORMATION, AND PROPAGATION PHASES......Page 48
XIII. CONCLUSION......Page 51
REFERENCES......Page 52
I. INTRODUCTION......Page 58
II. MECHANISMS OF HEMOSTASIS......Page 59
III. OVERVIEW OF GENETIC DETERMINANTS OF THROMBOSIS......Page 60
B. Factor V......Page 61
C. Prothrombin......Page 62
F. APC Receptor......Page 63
H. Fibrinogen......Page 64
V. FIBRINOLYTIC PROTEINS A. Plasminogen Activator Inhibtor-1......Page 65
A. GPIb......Page 66
B. GPIIb/IIIa......Page 67
VII. ENZYME/RECEPTOR POLYMORPHISMS A. Methytetrahydrofolate Reductase and Homocysteine......Page 68
C. Nitric Oxide Synthase......Page 71
D. ACE D......Page 72
REFERENCES......Page 73
I. NORMAL VASCULAR PHYSIOLOGY A. Anatomy......Page 82
B. Endothelial Control of Vascular Tone, Thrombosis, and Inflammation......Page 83
II. VASCULAR DYSFUNCTION AND ATHEROTHROMBOSIS A. Endothelial Dysfunction and Altered Vasomotion......Page 84
B. Endothelial Dysfunction and Prothrombosis......Page 85
C. Oxidative Stress and Vascular Dysfunction......Page 86
D. Vascular Dysfunction and Inflammation......Page 87
E. Role of Vascular Dysfunction in Acute Coronary Syndromes......Page 88
F. Vascular Dysfunction and Clinical Studies......Page 91
III. THERAPEUTIC IMPLICATIONS......Page 92
REFERENCES......Page 93
I. RHEOLOGY......Page 100
II. ARTERIAL WALL SUBSTRATE......Page 101
III. SYSTEMIC FACTORS......Page 102
B. Lipids......Page 103
C. Homocysteine......Page 104
IV. THROMBIN......Page 105
REFERENCES......Page 108
II. RISK FACTORS FOR ATHEROSCLEROSIS......Page 112
III. CELLULAR AND BIOLOGIC EVENTS: PATHOGENIC MECHANISMS......Page 113
A. Lesion Initiation......Page 114
B. Inflammatory Cell Recruitment and Foam Cell Generation......Page 116
C. Growth of Fibroproliferative Atheroma......Page 118
D. Advanced Lesions......Page 122
V. FUTURE DIRECTIONS......Page 124
REFERENCES......Page 125
II. EFFICACY TRIALS......Page 134
III. PHARMACOKINETIC PROPERTIES OF THROMBOLYTICS......Page 135
A. Absorption and Distribution......Page 136
B. Metabolism and Elimination......Page 139
IV. PHARMACODYNAMIC PROPERTIES OF THROMBOLYTICS......Page 140
B. Fibrin Specificity......Page 141
C. PAI-1 Resistance......Page 142
D. Drug Interactions......Page 143
REFERENCES......Page 144
II. WARFARIN A. History......Page 148
B. Pharmacodynamics......Page 149
C. Pharmacokinetics......Page 152
D. Clinical Application......Page 153
B. Pharmacodynamics......Page 155
C. Pharmacokinetics......Page 156
IV. LOW MOLECULAR WEIGHT HEPARIN......Page 158
A. Pharmacodynamics......Page 159
B. Pharmacokinetics......Page 160
VI. FONDAPARINUX......Page 163
A. Pharmacodynamics......Page 164
B. Pharmacokinetics......Page 166
REFERENCES......Page 168
I. EVOLUTION OF CLINICAL PHARMACY SERVICES......Page 174
II. IMPLEMENTING CLINICAL PHARMACY IN THE ACUTE CARE SETTING......Page 175
IV. CLINICAL PHARMACY IN THE CARDIOLOGY ACUTE CARE SETTING......Page 176
V. CLINICAL PHARMACY IN THE CARDIOLOGY TRANSITIONAL CARE SETTING......Page 177
VII. CONCLUSION......Page 179
REFERENCES......Page 180
I. INTRODUCTION......Page 184
A. Generalized Pharmacotherapy Clinics......Page 186
C. Specialized Pharmacotherapy Clinics......Page 187
E. Barriers to Pharmacists in Providing Pharmaceutical Care......Page 189
REFERENCES......Page 190
6-1 Cost-Effective Drug Selection......Page 194
REFERENCE......Page 195
I. ORAL ANTIPLATELET AGENTS......Page 196
II. INJECTABLE GP IIB/IIIA INHIBITORS......Page 197
III. TRIAL COMPARISONS (NUMBER NEEDED TO TREAT)......Page 199
IV. PHARMACOECONOMIC ANALYSES: CLINICAL TRIALS......Page 201
V. PHARMACOECONOMIC ANALYSES: CLINICAL PRACTICE EXPERIENCES......Page 202
VI. PHARMACOECONOMIC ANALYSES: COST PER LIFE-YEAR SAVED......Page 203
REFERENCES......Page 204
I. PHARMACOLOGICAL DIFFERENTIATION......Page 208
II. ANALYSIS OF CLINICAL EVIDENCE......Page 209
III. ECONOMIC ASSESSMENT IN PERSPECTIVE......Page 210
IV. CONCLUSION......Page 213
REFERENCES......Page 214
I. UFH VS. LMWHs......Page 216
II. DIFFERENTIATION OF EFFICACY......Page 217
IV. ECONOMICS......Page 218
REFERENCES......Page 219
II. PRINCIPAL MECHANISMS OF ACS......Page 222
A. Mechanical Obstruction and Acute Plaque Rupture......Page 223
B. Acute Thrombosis......Page 225
C. Inflammation and Infection......Page 229
III. SUMMARY......Page 240
REFERENCES......Page 241
II. CLASSIFICATION OF ACS......Page 256
III. ACUTE RISK ASSESSMENT IN NON–ST-ELEVATION ACS......Page 257
A. Acute Risk Models for Non–ST-Elevation ACS......Page 258
B. Diabetes......Page 261
IV. ACUTE RISK ASSESSMENT IN ST-ELEVATION ACS......Page 262
A. Predictive Value of ECG Parameters in ST-Elevation ACS......Page 263
B. Predictive Value of Early Angiography in ST-Elevation ACS......Page 265
A. The First 24–48 Hours......Page 266
B. After 24–48 Hours......Page 268
VI. RISK ASSESSMENT ALGORITHMS FROM REGISTRIES......Page 271
VIII. ASSESSMENT OF LONG-TERM RISK......Page 272
IX. NEWER CARDIAC MARKERS......Page 273
REFERENCES......Page 276
II. UNFRACTIONATED HEPARIN......Page 284
A. Tests......Page 285
B. Clinical Utility and Relevance......Page 286
III. LOW MOLECULAR WEIGHT HEPARINS......Page 288
B. Clinical Utility/Relevance......Page 289
IV. DIRECT THROMBIN INHIBITORS......Page 291
B. Clinical Utility/Relevance......Page 292
A. Tests......Page 293
B. Clinical Utility/Relevance......Page 294
VI. ASPIRIN RESISTANCE......Page 296
REFERENCES......Page 297
9-2 Clinical Trials of Combination Pharmacotherapy for ST-Elevation Acute Myocardial Infarction......Page 302
I. SHORTCOMINGS OF FIBRINOLYTIC THERAPY......Page 303
II. THEORETICAL RATIONALE FOR COMBINATION THERAPY......Page 304
III. CLINICAL TRIALS OF COMBINATION THERAPY: PILOT STUDIES......Page 305
IV. CLINICAL ENDPOINT STUDIES A. GUSTO V......Page 312
B. ASSENT-3......Page 313
V. DIRECT THROMBIN INHIBITORS IN COMBINATION WITH FIBRINOLYSIS......Page 314
VI. SUMMARY: CURRENT STATUS AND FUTURE DIRECTIONS......Page 316
REFERENCES......Page 318
I. UNSTABLE ANGINA AND NON–ST SEGMENT ELEVATION MYOCARDIAL INFARCTION......Page 322
II. ST SEGMENT ELEVATION MYOCARDIAL INFARCTION......Page 323
B. Acute Inferior and Right Ventricular STEMI......Page 324
C. Acute Lateral STEMI......Page 325
D. Acute Posterior STEMI......Page 326
III. CONFOUNDING PATTERNS......Page 328
REFERENCES......Page 332
I. CREATINE KINASE......Page 338
II. CK ISOENZYMES......Page 339
V. CARDIAC-SPECIFIC TROPONINS......Page 340
VI. RENAL INSUFFICIENCY......Page 341
VIII. CLINICAL USE OF CARDIAC BIOMARKERS: RECOMMENDATIONS......Page 342
REFERENCES......Page 344
A. Radionuclide Myocardial Perfusion Imaging......Page 350
B. Echocardiography......Page 353
II. EVALUATION OF COMPLICATIONS FOLLOWING MYOCARDIAL INFARCTION......Page 354
A. Radionuclide Myocardial Perfusion Imaging......Page 355
B. Echocardiography......Page 356
IV. CONCLUSION......Page 357
REFERENCES......Page 358
II. HISTORICAL BACKGROUND......Page 362
A. Mechanical Valves......Page 363
B. Biological Valves......Page 366
C. Annuloplasty Rings......Page 370
A. Thrombogenicity of Prosthetic Materials......Page 372
B. Mechanical Components......Page 373
C. Biological Components......Page 374
D. Sewing Ring......Page 377
E. Annuloplasty Rings......Page 378
G. Specific Flow Patterns of Mechanical Valves......Page 379
V. CLINICAL APPROACH TO PATIENTS WITH PROSTHETIC HEART VALVES......Page 380
VII. MANAGEMENT GUIDELINES......Page 381
REFERENCES......Page 383
II. IDENTIFICATION OF PATIENTS WITH HYPERCOAGULABLE STATES......Page 386
III. HYPERCOAGULABLE STATES RESPONSIBLE FOR ARTERIAL THROMBOEMBOLIC DISEASE A. Inherited Hypercoagulable States......Page 387
B. Acquired Hypercoagulable States......Page 391
IV. LABORATORY TESTING FOR HYPERCOAGULABLE STATES......Page 394
REFERENCES......Page 395
II. HEMORRHAGE......Page 402
A. Intracranial Hemorrhage......Page 403
B. Nonintracranial Hemorrhage......Page 404
C. Hemorrhage Rates with Specific Fibrinolytic Agents......Page 405
D. Hemorrhage with Antithrombotic Therapy......Page 406
E. Hemorrhage with Antiplatelet Therapy......Page 409
F. Prediction of Hemorrhage......Page 410
G. Management of Hemorrhage......Page 412
III. HEMATOLOGICAL COMPLICATIONS......Page 414
IV. IMMUNOLOGICAL COMPLICATIONS......Page 415
REFERENCES......Page 416
I. PRIMARY ANGIOPLASTY......Page 424
II. ADVANTAGES OF PCI OVER THROMBOLYTIC THERAPY A. Availability......Page 426
B. Efficacy......Page 427
C. Complications......Page 428
E. Patients in Shock......Page 429
III. STENTS......Page 430
IV. OTHER DEVICES......Page 431
V. RESCUE PCI......Page 432
VI. ROUTINE PTCA AFTER THROMBOLYSIS......Page 433
REFERENCES......Page 435
II. PERCUTANEOUS CORONARY INTERVENTION......Page 440
III. UNFRACTIONATED HEPARIN......Page 441
IV. LOW MOLECULAR WEIGHT HEPARIN......Page 444
V. DIRECT THROMBIN INHIBITORS......Page 448
VI. OTHER ANTICOAGULANT AGENTS......Page 451
REFERENCES......Page 453
II. ASPIRIN......Page 460
III. THIENOPYRIDINES: TICLOPIDINE AND CLOPIDOGREL......Page 461
IV. PLATELET GP IIB/IIIA BLOCKADE......Page 464
A. Abciximab......Page 466
B. Eptifibatide......Page 469
C. Tirofiban......Page 471
V. FUTURE ANTIPLATELET THERAPY......Page 472
REFERENCES......Page 473
II. FOCAL LESIONS......Page 480
B. Small Vessels......Page 484
C. Chronic Occlusions......Page 485
D. Acute Myocardial Infarction......Page 486
E. Saphenous Vein Grafts......Page 487
IV. NEW DEVELOPMENTS IN STENTING A. Stent Design and Deployment......Page 489
C. Covered Stents......Page 491
VI. CONCLUSIONS......Page 492
REFERENCES......Page 493
I. INTRODUCTION......Page 500
III. HEPARINOIDS......Page 501
IV. DIRECT THROMBIN INHIBITORS......Page 502
V. THIENOPYRIDINES......Page 504
VI. GLYCOPROTEIN IIB/IIIA INHIBITORS......Page 507
VIII. COMPLICATIONS OF ANTITHROMBOTICS......Page 510
X. CONCLUSION......Page 512
REFERENCES......Page 513
I. DIRECT THROMBIN INHIBITORS......Page 522
A. HIRUDIN......Page 523
B. HIRULOG......Page 526
C. Univalent Direct Thrombin Inhibitors......Page 529
A. LMWHs in Unstable Angina......Page 531
B. LMWHs in Conjunction with IIb/IIIa Inhibitors for Medical Management of UA......Page 533
C. LMWHs in AMI/STEMI......Page 534
D. LMWHs in PCI......Page 536
III. SUMMARY AND FUTURE DIRECTIONS......Page 537
REFERENCES......Page 546
II. FACILITATED ANGIOPLASTY IN AMI......Page 552
III. PHARMACOLOGICAL REPERFUSION STRATEGIES......Page 553
IV. MECHANICAL PERFUSION AS AN ALTERNATIVE TO THROMBOLYSIS......Page 554
V. CORONARY STENTING IN ACUTE MYOCARDIAL INFARCTION......Page 557
VI. THE ROLE OF GLYCOPROTEIN IIB IIIA INHIBITORS IN ACUTE MYOCARDIAL INFARCTION A. Glycoprotein IIb IIIa Inhibitors and Thrombolytic Therapy......Page 558
B. Glycoprotein IIb IIIa Inhibitors and Primary PCI......Page 560
VII. COMBINING PHARMACOLOGICAL AND MECHANICAL STRATEGIES......Page 562
VIII. IMPORTANCE OF TIMI 3 FLOW BEFORE PRIMARY PCI......Page 563
IX. MICROVASCULAR FLOW AS A DETERMINANT OF CLINICAL OUTCOMES......Page 565
X. MODULATORS OF RESPONSE TO THERAPY: NECROSIS, INFLAMMATION, PRECONDITIONING......Page 566
B. New Approaches and Technologies......Page 567
XII. CONCLUSION......Page 570
REFERENCES......Page 571
II. PATHOPHYSIOLOGY OF RESTENOTIC LESION FORMATION......Page 582
III. MECHANISMS OF RESTENOSIS PREVENTION BY IONIZING RADIATION......Page 583
V. TECHNIQUES OF INTRACORONARY RADIATION DELIVERY: RADIOACTIVE STENTS......Page 584
VII. AAPM RECOMMENDATIONS FOR USE OF CORONARY RADIATION SYSTEMS......Page 585
A. De Novo Lesions......Page 586
B. Restenosis Lesions......Page 587
B. The Edge Effect......Page 588
D. Late Results and Catch-Up Effects......Page 589
REFERENCES......Page 590
II. BASIC PRINCIPLES......Page 594
III. SPECIFIC LABORATORY TESTS TO MONITOR ANTICOAGULATION A. Prothrombin Time......Page 595
B. Whole Blood Clotting Time......Page 597
C. Dry Reagent Technology......Page 600
D. Ecarin Clotting Time......Page 602
E. Viscoelastic Measures of Coagulation......Page 603
F. ENOX Test......Page 607
G. Monitoring of Platelet Function......Page 608
REFERENCES......Page 610
II. ACUTE TREATMENT OF VENOUS THROMBOEMBOLIC DISEASE......Page 618
A. Heparin......Page 619
C. Direct Thrombin Inhibitors......Page 620
D. Fondaparinux......Page 621
III. PROPHYLAXIS A. Secondary Prevention......Page 622
B. Primary Prevention of Venous Thromboembolism......Page 623
C. Timing of Prophylaxis......Page 625
D. Duration of Primary Prophylaxis for Venous Thromboembolism......Page 626
REFERENCES......Page 627
II. CHRONIC ANTICOAGULATION IN CARDIAC DISEASE A. Prosthetic Heart Valves......Page 638
B. Atrial Fibrillation......Page 639
C. Dilated Cardiomyopathy......Page 642
A. Point-of-Care Prothrombin Time/INR Instruments......Page 643
B. Anticoagulation Self-Management: Evidence-Based Practice......Page 644
REFERENCES......Page 645
II. ACUTE APPLICATIONS A. Percutaneous Coronary Interventions......Page 650
B. Acute Coronary Syndromes......Page 664
C. Acute Stroke......Page 670
III. CHRONIC APPLICATIONS A. Atherosclerosis......Page 671
B. Percutaneous Coronary Interventions......Page 679
REFERENCES......Page 680
III. ADVANTAGES OF LSTs OVER META-ANALYSIS OF MULTIPLE SMALLER TRIALS......Page 692
V. LARGE SIMPLE TRIAL CONCEPTS A. LST Organization......Page 693
B. Interpretation of LST Results......Page 696
C. Hypothesis Testing......Page 697
E. Intent-to-Treat Analysis......Page 698
A. Mortality-Powered Trials in Acute MI–Fibrinolytic Therapy......Page 699
B. Multiple Endpoint LSTs in ACS–Antithrombotic Therapy......Page 700
REFERENCES......Page 701
A. The Cohort Study......Page 704
B. Case-Control Studies......Page 706
A. The Randomized Clinical Trial......Page 707
III. APPLICATION OF RESEARCH DESIGN PRINCIPLES......Page 715
REFERENCES......Page 716
I. INTRODUCTION A. Antithrombotic Drugs in Bite Size Pieces......Page 720
A. Aspirin......Page 721
C. Warfarin......Page 723
III. DEVELOPING ANTITHROMBOTIC DRUGS......Page 724
C. Focused Clinical Trials......Page 725
IV. MEASURING DRUG DEVELOPMENT A. How Long Does It Take?......Page 727
C. What Is the Likelihood of Successful Product Commercialization?......Page 728
V. REGULATORY CONSIDERATIONS......Page 730
B. Good Clinical Practice......Page 731
VI. MANUFACTURING ANTITHROMBOTIC DRUGS......Page 732
VII. MARKETING ANTITHROMBOTIC DRUGS A. What Is Marketing?......Page 733
C. Product, Service, or Both?......Page 734
E. Exchange, Transactions, and Relationships......Page 735
G. Global Challenges......Page 737
B. Oral Antiplatelet Agents......Page 739
D. Heparins......Page 740
IX. Future Industrial Perspectives......Page 742
REFERENCES......Page 743
Index......Page 748
Back cover......Page 760