Opie’s Cardiovascular Drugs: A

Front Cover......Page 1
Inside Front cover......Page 2
Opie’s Cardiovascular Drugs: A Companion to Braunwald’s Heart Disease......Page 5
Copyright......Page 6
Dedication......Page 7
Contributors......Page 9
Foreword......Page 13
Preface......Page 15
Acknowledgments......Page 17
Contents......Page 19
Braunwalds Heart Disease Family of Books......Page 20
Introduction......Page 23
Secondary effects of β-receptor blockade......Page 26
Cardiovascular Effects of β-Blockade......Page 28
Effects on coronary flow and myocardial perfusion......Page 29
Plasma half-lives......Page 30
First-pass hepatic metabolism......Page 31
Pharmacokinetic interactions......Page 32
Angina Pectoris......Page 38
Vasospastic angina......Page 40
Acute Coronary Syndrome......Page 41
Early ST-elevation myocardial infarction......Page 42
Benefits of postinfarct β-blockade......Page 43
Other Cardiac Indications for β-Blockers......Page 44
Impact of POISE study......Page 45
Esophageal varices......Page 46
β-blocker ``generations.´´......Page 47
Antiarrhythmic β-blockers......Page 48
Bisoprolol......Page 50
Penbutolol......Page 51
Respiratory disease......Page 53
Side Effects of β-Blockers......Page 54
Quality of life and libido......Page 55
Overdose of β-Blockers......Page 56
Summary......Page 59
Introduction......Page 61
Coronary and peripheral vasodilatory effects......Page 63
Endothelium and vascular mechanisms......Page 64
Short-Acting Nitrates for Acute Exertional Angina......Page 67
Long-Acting Nitrates for Angina Prophylaxis......Page 70
Acute Heart Failure and Acute Pulmonary Edema......Page 72
Beneficial Combination of Isosorbide Dinitrate and Hydralazine in African American Patients With Heart Failure......Page 73
Nitrate Interactions With Other Drugs......Page 74
Nitrate Tolerance......Page 76
Combination Therapy for Angina......Page 77
Introduction......Page 79
Calcium Channels: L and T Types......Page 81
Nondihydropyridine (non-DHP) or Heart Rate-Lowering (HRL) CCBs......Page 83
Verapamil......Page 84
Pharmacokinetics......Page 85
Angina and myocardial ischemia......Page 87
Postinfarction secondary prevention......Page 90
Side effects......Page 91
Contraindications to verapamil......Page 93
β-blockers......Page 94
Therapy of verapamil toxicity......Page 96
Diltiazem for supraventricular arrhythmia......Page 97
Postinfarction secondary prevention......Page 98
Drug interactions and combinations......Page 99
Nifedipine: The Prototypic and First DHP CCB......Page 100
Exertional angina......Page 101
Minor side effects......Page 102
Combination with β-blockers and other drugs......Page 103
Amlodipine: The First of the Second-Generation DHPs......Page 106
Hypertension......Page 107
Contraindications, cautions, and side effects......Page 109
Third-Generation Dihydropyridines......Page 110
Summary......Page 111
Newer (Nontraditional) Antianginal Agents (or Metabolic and Other Nontraditional Antianginal Agents)......Page 112
Ranolazine......Page 113
Trimetazidine......Page 114
Nicorandil......Page 115
Summary......Page 116
References......Page 117
Introduction......Page 119
Drug Class Overview and Guidelines......Page 122
Mechanism of Action......Page 128
Differences Within Class......Page 129
Clinical Application......Page 131
Volume depletion......Page 133
Diabetes......Page 134
Sulfonamide Sensitivity......Page 135
Differences Among Drugs in Class......Page 136
Clinical Application......Page 139
Drug Interactions......Page 140
Mechanism of Action......Page 141
Clinical Application......Page 143
Side Effects......Page 146
Mechanism of Action......Page 147
Differences Among Drugs in Class......Page 148
Clinical Application......Page 150
Side Effects......Page 151
Mechanism of Action......Page 153
Clinical Application......Page 154
Side Effects......Page 155
Differences Among Drugs in Class......Page 156
Clinical Application......Page 158
Drug Interactions......Page 160
Differences Among Drugs in Class......Page 161
Side Effects and Drug Interactions......Page 162
Differences Among Drugs in Class......Page 163
Clinical Application......Page 164
Side Effects......Page 165
Mechanisms of Action......Page 166
Clinical Application......Page 167
References......Page 168
Introduction......Page 169
Diuretics......Page 173
Vasodilators......Page 179
Organic Nitrates......Page 180
Nesiritide......Page 182
Novel Vasodilators......Page 183
Dobutamine......Page 185
Dopamine......Page 187
Isoproterenol......Page 188
Calcium Sensitizers......Page 189
Omecamtiv Mecarbil......Page 191
Vasopressors......Page 192
Acute Coronary Syndromes......Page 194
Right Ventricular Heart Failure......Page 195
Introduction......Page 196
Neurohormonal Activation......Page 198
β-Blockers......Page 199
Angiotensin-Converting Enzyme Inhibitors......Page 205
Angiotensin-converting Enzyme Inhibitors or β-Blockers First......Page 208
Angiotensin Receptor Blockers......Page 209
Angiotensin Receptor Neprilysin Inhibitors......Page 211
Mineralocorticoid-Receptor Antagonists......Page 213
Sodium-Glucose Cotransporter-2 Inhibitors......Page 215
Diuretics......Page 216
Combination of Hydralazine Plus Isosorbide Dinitrate......Page 218
If Channel Inhibitor......Page 219
Digoxin......Page 221
Iron Supplementation and Anemia......Page 224
Fish Oil and Marine Omega-3 Polyunsaturated Fatty Acids......Page 226
Oral Anticoagulants and Antiplatelet Therapy......Page 227
Statins......Page 229
Antiarrhythmic Agents......Page 230
Introdution......Page 232
Diuretics......Page 235
Renin-Angiotensin Blockade: Angiotensin Converting Enzyme Inhibitors and Angiotensin Receptor Blockers......Page 236
Mineralocorticoid Receptor Antagonists......Page 237
Angiotensin Receptor Neprilysin Inhibitors......Page 238
β-Blockers......Page 239
Digoxin, Calcium Channel Blockers, and Ivabradine......Page 240
Nitric Oxide and cGMP Signaling: Phosphodiesterase-5 Inhibitors, Nitrates, and Soluble Guanylate Cyclase Stimulators......Page 241
Other Medications......Page 242
Drugs That Should Be Avoided or Used Cautiously in Heart Failure......Page 243
Pharmacological Treatment of Selected Cardiomyopathies......Page 247
Summary......Page 249
References......Page 251
Metabolic Syndrome and Prediabetes......Page 253
Risks of Metabolic Syndrome......Page 255
Lifestyle Changes to Slow the Onset of Diabetes......Page 257
Blood Pressure and Lifestyle......Page 258
Which Drugs Halt the Slide to Diabetes?......Page 259
Cardiovascular Disease Risk Assessment......Page 260
Duration of Diabetes......Page 261
Age of Onset......Page 262
Coronary Artery Calcium Testing......Page 263
Guideline Recommendations on Glycemic Control......Page 264
ACCORD......Page 265
Summary......Page 266
Importance of Large Cardiovascular Disease Outcome Trials......Page 267
Glycemic control......Page 272
Weight loss......Page 273
Side Effects......Page 274
Mechanisms of Action......Page 275
EMPA-REG......Page 277
DECLARE-TIMI-58......Page 278
Experimental Drugs......Page 279
Mechanism of Action......Page 280
Differences Among Drugs in Class......Page 281
LEADER......Page 282
REWIND......Page 283
Drug Class Overview......Page 284
TECOS......Page 285
Mechanisms of Action......Page 286
Glycemic control......Page 287
Lipid profiles......Page 288
Mechanisms of Action......Page 289
Cardiovascular effects......Page 290
Drug Class Overview......Page 291
Glycemic control......Page 292
Drug Interactions or Major Restriction......Page 293
Hypoglycemia and Cardiovascular Risk......Page 294
Diabetes Drugs and Hypoglycemia......Page 295
Guidelines......Page 296
Oral Semaglutide......Page 297
References......Page 298
Drug Class Overview and Guidelines......Page 299
Weight Loss Intervention......Page 300
Guidelines......Page 301
Centrally Acting Drugs......Page 303
Lifestyle and Diet Interventions......Page 305
Bariatric Surgery and Medical Devices......Page 308
Orlistat......Page 309
Phentermine/Topiramate......Page 310
Lorcaserin......Page 312
Naltrexone/Bupropion......Page 314
Glucose-Like Peptide (GLP)-1 Receptor Agonist......Page 315
Conclusion......Page 318
References......Page 320
Chapter 6: Lipid-Modifying Drugs......Page 321
Inflammation and Atherogenesis......Page 323
C-Reactive Protein......Page 326
Primary Prevention......Page 327
Secondary Prevention......Page 328
Total Cholesterol and Low-Density Lipoprotein Cholesterol......Page 329
High-Density Lipoprotein Cholesterol......Page 330
Triglycerides......Page 331
Metabolic Syndrome......Page 333
Secondary Dyslipidemias......Page 334
Diabetic Patients......Page 336
Older Adults......Page 338
Pregnant Women......Page 339
Diet......Page 340
Statins: 3-Hydroxy-3-Methylglutaryl Coenzyme A Reductase Inhibitors......Page 341
How Intensive Should Statin Therapy Be?......Page 342
Liver Damage, Myopathy, New Diabetes, and Cognitive Side Effects......Page 345
Dose, Effects, and Side Effects......Page 347
Pravastatin (Pravachol, Lipostat)......Page 348
Major Trials......Page 349
Dose, Side Effects, and Safety......Page 350
Primary Prevention......Page 351
Rosuvastatin (Crestor)......Page 352
Dosage, Effects, and Side Effects......Page 353
Pitavastatin (Livalo)......Page 354
Combination Therapy......Page 355
Cholesterol Absorption Inhibitors: Ezetimibe (Zetia, Vytorin, Nexlizet)......Page 356
Dosage and Effect......Page 358
Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9) Inhibitors (Repatha, Praluent)......Page 359
Indications......Page 361
In Development: Inclisiran......Page 362
Bempedoic Acid (Nexletol, Nexlizet [US]; Nilemdo, Nustendi [EU])......Page 364
Dosage, Effects, and Side Effects......Page 365
Omega-3 Fatty Acids (Fish Oils; Lovaza, Vascepa, Epanova)......Page 366
Side Effects......Page 368
Combined Statin Plus Fibrate......Page 369
Fenofibrate (Tricor, Trilipix, Lipofen, Antara, Lofibra)......Page 370
Major Trials......Page 371
Bezafibrate......Page 372
Bile Acid Sequestrants: Resins (Questran, Welchol, Colestid)......Page 373
Nicotinic Acid (Niacin; Niaspan)......Page 374
Dose, Side Effects, and Contraindications......Page 375
Targeting Triglycerides......Page 376
Diabetes......Page 378
Hypertriglyceridemia......Page 379
References......Page 380
Chapter 7: Drugs Targeting Inflammation......Page 381
Basic Concepts of Inflammation Biology......Page 382
Stimuli for the Inflammatory Response......Page 384
Central Hubs of Inflammatory Signaling (see Fig. 7.2)......Page 395
Mediators......Page 398
Conclusions, Challenges, and Future Perspective......Page 405
References......Page 408
Coagulation, Thrombosis, and Hemostasis......Page 409
Arterial Thrombosis......Page 410
Platelet Deposition......Page 411
Activation of Coagulation Proteases......Page 412
Coagulation on Cellular Surfaces......Page 414
Contact and Intrinsic Pathway-Mediated Coagulation......Page 415
Human FXI......Page 416
Human FXII......Page 417
Plasma Proteins......Page 418
Platelets......Page 419
Platelets and Neutrophil Extracellular Traps......Page 420
Pharmacokinetics......Page 422
Primary Prevention of Vascular Events......Page 424
Stable Cardiovascular Disease......Page 425
Aspirin Before CABG......Page 427
Percutaneous Coronary Intervention......Page 428
Aspirin Response Variability......Page 429
Drug Therapy After Peripheral Artery Revascularization......Page 430
Contraindications to Aspirin......Page 431
Pharmacokinetics......Page 432
Pharmacodynamics......Page 433
Aspirin......Page 434
Pharmacokinetics......Page 435
Clinical Experience......Page 436
Pharmacokinetics......Page 437
Pharmacokinetics......Page 440
Peripheral Artery Disease......Page 441
Coronary Arterial Stenting......Page 442
Pre-PCI Treatment, Duration of Therapy, and Clinical Benefit......Page 443
Duration of Dual Antiplatelet Therapy After PCI......Page 444
ST-Segment Elevation Myocardial Infarction (STEMI)......Page 445
MitraClip Implantation and Transcutaneous Mitral Valve Replacement (TMVR)......Page 446
Pharmacokinetics......Page 447
Acute Coronary Syndrome......Page 448
Acute Coronary Syndrome......Page 449
Peripheral Artery Disease......Page 450
Platelet-Directed Therapies and Coronary Stent Thrombosis......Page 451
High On-Treatment Platelet Reactivity and Post-PCI Events......Page 452
Pharmacogenomics and P2Y12 Inhibitor Therapy......Page 455
What Is the Role of Platelet Function Testing in Routine Clinical Practice?......Page 457
Deescalation of Therapy Employing Platelet Function Tests......Page 458
Periprocedural Management of Antiplatelet Therapy and Coronary Artery Bypass Grafting......Page 459
Periprocedural Management of Antiplatelet Therapy and GI Procedures......Page 460
Intravenous Platelet GPIIb/IIIa Receptor Antagonists......Page 468
Pharmacodynamics......Page 469
Clinical Experience......Page 470
Clinical Experience......Page 472
Clinical Experience......Page 473
Pharmacodynamics......Page 475
Clinical Experience......Page 476
Bleeding and Clinical Outcomes......Page 477
Supporting Data for Attenuating P2Y12 Antagonist Pharmacodynamic Effects......Page 478
The Challenge of Attenuating Ticagrelors Pharmacodynamic Effect......Page 479
Summary of Recommendations in Patients With ACS......Page 480
Anticoagulants......Page 482
Direct Thrombin Inhibitors......Page 487
Pharmacokinetics......Page 488
HIT Therapy......Page 489
Acute Myocardial Infarction......Page 490
Left Ventricular Device Thrombosis......Page 493
Synthetic Pentasaccharide: Fondaparinux......Page 494
Clinical Experience......Page 495
Clinical Experience......Page 497
Combined Pharmacology and Coronary Interventional Strategies......Page 499
LMWH and Platelet GPIIb/IIIa Receptor Antagonist Combination Therapy......Page 501
Pharmokinetics......Page 502
Clinical Experience......Page 503
Clinical Experience......Page 504
Impact of Renal Insufficiency......Page 505
Pharmacokinetics......Page 506
Dosing Strategies: An Opportunity for Improved Safety......Page 507
Bleeding and Outcomes in ACS......Page 508
Pharmacokinetics and Drug Disposition......Page 509
Dabigatran......Page 517
Rivaroxaban......Page 518
Apixaban......Page 519
Betrixaban......Page 520
Venous thromboembolism......Page 521
Atrial Fibrillation......Page 522
Bleeding With Dabigatran in AF......Page 523
Venous thromboembolism......Page 524
Atrial Fibrillation and PCI......Page 525
Heart Failure......Page 526
Ablation......Page 527
Pharmacokinetics......Page 528
Atrial Fibrillation......Page 529
Ablation......Page 530
Edoxaban......Page 531
Atrial Fibrillation......Page 532
Pharmacokinetics......Page 533
Betrixaban-Associated Bleeding......Page 534
Dosing......Page 535
Dose Modifications......Page 536
Warfarin-Associated Bleeding Risk......Page 537
Ventricular Assist Devices......Page 538
Prosthetic Heart Valves......Page 539
Treatment of VKA-Associated Bleeding......Page 540
Idarucizumab......Page 541
Andexanet Alfa......Page 543
Achieving Good Hemostasis......Page 545
Conclusions......Page 549
References......Page 553
Antiarrhythmic Drugs......Page 555
Classification......Page 556
Clinical use......Page 558
Drug interactions and combination......Page 564
Procainamide......Page 565
Side effects......Page 566
Ajmaline......Page 568
Clinical use......Page 570
Lidocaine failure for VT and VF......Page 572
Side effects......Page 574
Class IC: Flecainide and Propafenone......Page 575
Clinical use......Page 576
Side effects......Page 578
Clinical use......Page 579
Side effects......Page 580
Pharmacokinetics......Page 581
Dose......Page 583
Side effects......Page 585
Pharmacokinetics......Page 586
Clinical use......Page 588
Dose......Page 589
Side effects......Page 591
Drug interactions and combination......Page 593
Clinical use......Page 594
Dose......Page 595
Clinical use......Page 596
Pure Class III Agents: Ibutilide, Dofetilide, and Vernakalant......Page 597
Side effects......Page 598
Clinical use......Page 599
Pharmacokinetics......Page 600
Class IV Agents......Page 601
Dose......Page 603
Clinical use......Page 604
Clinical use......Page 606
Drug interactions and combination......Page 607
New Developments in Antiarrhythmics......Page 608
Atrial Fibrillation......Page 610
Preexcited Atrial Fibrillation......Page 611
Ventricular Arrhythmias (VT, VF)......Page 612
Summary......Page 613
References......Page 614
Drugs for Patients With Peripheral Artery Disease......Page 615
Drug Class Overview and Guidelines......Page 619
Antihypertensive Therapies......Page 620
Antiplatelet Monotherapy......Page 622
More Intensive Antiplatelet Therapy......Page 623
Low-Dose Anticoagulation......Page 625
Low-Density Lipoprotein Lowering......Page 626
Other Lipid-Modifying Agents......Page 629
Glucose-Lowering Therapies......Page 630
SGLT-2 Inhibitors......Page 631
GLP1 Agonists......Page 632
Therapies for Symptoms......Page 633
Metabolic Drugs......Page 635
Parenteral Anticoagulants......Page 636
Oral Anticoagulants......Page 637
Drugs for Aortic Aneurysm and Dissection......Page 638
Initial Medical Management of Aortic Dissection......Page 639
Long-term Therapy in Aortic Dissection and Aneurysm......Page 640
Steroid Sparing Agents......Page 641
Pharmacotherapies......Page 643
References......Page 644
Pathobiology of Pulmonary Arterial Hypertension......Page 645
Updates in the Clinical Classification of PAH......Page 646
Prostanoids......Page 647
Calcium Channel Blockers (CCBs)......Page 648
Risk Stratification......Page 649
Initial Combination Therapy......Page 650
Initial Monotherapy......Page 652
Sequential Therapy......Page 654
Prostanoids......Page 656
Phosphodiesterase Type 5 Inhibitors......Page 658
Endothelin Receptor Antagonists......Page 659
Epoprostenol Versus Parenteral Treprostinil......Page 660
Phosphodiesterase Type 5 Inhibitors......Page 664
Data for Use......Page 666
Prostanoids......Page 668
IP Receptor Agonists......Page 669
Phosphodiesterase Type 5 Inhibitors......Page 670
Side Effects......Page 671
Phosphodiesterase type 5 inhibitors......Page 672
IP Receptor Agonists......Page 673
Endothelin Receptor Antagonists......Page 674
Experimental Drugs......Page 675
References......Page 677
Index......Page 679
Inside Back Cover......Page 723