Dietrich Strödter & Frans Santosa 
State-of-the-art Treatment of Coronary Heart Disease 

The treatment of coronary artery disease (CAD) encompasses many strategies all of which aim to improve symptoms and prognosis. While in the acute coronary syndrome, early revascularisation (usually by means of PCI and stent implantation) is the urgent goal of treatment, drug therapy initially has only a supportive role here but is also important for improving prognosis. The situation is reversed in the case of the treatment of chronic stable CAD: here conservative drug therapy has the dominant role and if implemented optimally is so successful that the prognosis cannot be further improved with additional PCI and stent implantation. Therefore, the indication for revascularisation should not only be based on an angiographic but also on a functional (FFR, fractional flow reserve) assessment of the stenosis.
This book is therefore a critical presentation of the benefit of treatment strategies in the different forms of CAD. In addition to the value of lifestyle changes, it deals with the evaluation of the various drug therapies, invasive procedures such as PCI and stent implantation, bypass surgery and electrotherapeutic measures with ICD, CRT and cardiac pacemakers. The authors have succeeded in producing a textbook that is not just of interest to the attending doctor but also for patients affected by the disease. A textbook from the viewpoint: what is optimal? What is economic? What is evidence-based?

Innehållsförteckning

1.From Primary to Secondary Prevention30
1.1.Definition30
1.2.Risk factors for atherosclerosis30
1.3.Aims of secondary prevention32
1.4.Primary vs secondary prevention32
1.5.Risk stratification33
1.6.Blood pressure/Hb A1c goals36
1.7.Hb A1c target in diabetics38
1.8.Lipids38
1.9.Non-pharmacological therapeutic measures40
1.10.Lifestyle and mortality risk40
1.11.Who has the highest cardiovascular risk?41
1.12.NSAIDs and cardiovascular risk42
1.13.Vitamin D and atherosclerosis42
1.14.Exposure to ambient air pollution and noise42
1.15.MI risk with testosterone and PDE 5 inhibitors43
1.16.Cardiovascular risk and events in low, middle and high income countries43
1.17.Summary43
1.18.References43
2.Manifestations and Prognosis of CAD47
2.1.Manifestations of atherosclerosis47
2.2.Manifestations of CAD47
2.3.Prognosis of CAD49
2.4.Prognosis and gender51
2.5.Prognosis in renal insufficiency51
2.6.Prognosis and diabetes52
2.7.Prognosis and type of medical care53
2.8.Prognosis for myocardial infarction53
2.9.An obesity paradox in ACS?54
2.10.Decrease in CAD mortality?54
2.11.Prognosis with guideline-oriented therapy?56
2.12.National differences in prognosis for AMI56
2.13.Refractory a.p. – Prognosis?56
2.14.A.p. without CHD?57
2.15.Cardiac syndrome X57
2.16.Prognosis in ACS and AV III or Mobitz II57
2.17.Radial vs femoral access in ACS – The MATRIX study57
2.18.Summary58
2.19.References58
3.From the Endothelial Defect to Myocardial Infarction61
3.1.The importance of the endothelium61
3.2.The acetylcholine test as a method to demonstrate endothelial dysfunction62
3.3.Clinical impact of endothelial dysfunction during stress62
3.4.Endothelial dysfunction as a prognostic indicator63
3.5.Endothelial progenitor cells63
3.6.Atherosclerosis in the coronary region64
3.7.From atherothrombosis to the acute syndrome66
3.8.Histomorphology of vulnerable plaques67
3.9.Remodelling of the left ventricle after myocardial infarction67
3.10.Collateral formation in atherosclerosis68
3.11.The natural course of atherosclerosis69
3.12.Summary69
3.13.References70
4.Pathophysiology of CAD and Strategies for Secondary Prevention72
4.1.Coronary insufficiency72
4.2.Determinants of the myocardial O2 requirement73
4.3.Heart rate73
4.4.Antianginal agents and their points of attack74
4.5.Strategies for secondary prevention75
4.6.Therapeutic priorities depending on the form of presentation of CAD76
4.7.Stem cell therapy77
4.8.Myocardial infarction due to embolism77
4.9.Summary77
4.10.References78
5.Nitrates and Other Antianginal Agents80
5.1.Mechanism of action of nitrates80
5.2.Nitrate drugs80
5.3.Do nitrates prolong survival in CAD?81
5.4.Nitrates in secondary prevention82
5.5.Molsidomine82
5.6.Trapidil83
5.7.Nicorandil, a potassium channel opener 83
5.8.Ranolazine84
5.9.Trimetazidine85
5.10.Guidelines for anti-anginal drugs85
5.11.Summary86
5.12.References86
6.Beta-Blockers89
6.1.Mechanism of action of beta-blockers89
6.2.Classification of beta-blockers89
6.3.Differences between beta-blockers89
6.4.Treatment aims on beta-blockers90
6.5.Beta-blockers in post-infarct patients90
6.6.Who benefits most?91
6.7.Do all beta-blockers have a secondary prevention effect?93
6.8.Can beta-blockers be used for secondary prevention in CAD without infarction?93
6.9.Beta-blockers in heart failure95
6.10.Third-generation beta-blockers95
6.11.Beta-blockers in LV dysfunction after infarction – The CAPRICORN study95
6.12.Guidelines97
6.13.Summary98
6.14.References99
7.Calcium antagonists102
7.1.Mechanism of action of calcium antagonists102
7.2.Differences between the calcium antagonists102
7.3.Calcium antagonists in stable angina102
7.4.Dihydropyridines in postinfarct patients103
7.5.Diltiazem in postinfarct patients103
7.6.Verapamil in postinfarct patients104
7.7.Hypertensive vs normotensive postinfarct patients105
7.8.Third-generation calcium antagonists in CAD105
7.9.AHA/ACCF and ESC guidelines107
7.10.Summary108
7.11.References108
8.ACE Inhibitors110
8.1.Mechanism of action110
8.2.Pathophysiological basis of ACE inhibitor treatment110
8.3.ACE inhibitors and aspirin112
8.4.Postinfarction studies with ACE inhibitors113
8.5.ACE inhibitors and risk of AF116
8.6.The HOPE study116
8.7.ACE inhibitors and rate of infarction118
8.8.ACE inhibitors in association with and after PTCA – The QUIET study118
8.9.ACE inhibitors in CAD patients with a lower risk119
8.10.AHA/ACCF and ESC guidelines121
8.11.Summary122
8.12.References122
9.AT1 Receptor Blockers125
9.1.The mechanism of action125
9.2.AT1 receptor blockers and pleiotropic effects125
9.3.Clinical studies in CAD126
9.4.Combination of ACE inhibitor plus AT1 receptor blocker129
9.5.ACCF/AHA and ESC guidelines129
9.6.Summary130
9.7.References130
10.Statins and Non-Statins (Ezetimibe, PCSK9 Inhibitors)132
10.1.Situation before the statin era132
10.2.Mechanism of action of the statins132
10.3.A comparison of statins132
10.4.Statins and dose-effect relationship133
10.5.Statins in secondary prevention – The evidence from studies134
10.6.The time for using a statin during and after acute coronary syndrome138
10.7.Statins and number of revascularisations139
10.8.Statins after CABG and PTCA139
10.9.Statins in PTCA140
10.10.Statins before PCI?141
10.11.Who benefits from LDL lowering? Younger or older patients?142
10.12.Additional effects of statins142
10.13.The greater the LDL reduction, the better145
10.14.Statins in high-risk patients150
10.15.Two maximum statin doses – The SATURN trial151
10.16.Statins and diabetes risk152
10.17.Non-statins152
10.18.LDL treatment targets today – The guidelines155
10.19.Summary159
10.20.References160
11.Antiplatelet Agents165
11.1.Antiplatelet agents – An overview165
11.2.Mechanism of action of antiplatelet agents165
11.3.Molecular target of the thienopyridines166
11.4.Prasugrel vs clopidogrel166
11.5.Ticagrelor and cangrelor167
11.6.Clopidogrel vs prasugrel vs ticagrelor167
11.7.Glycoprotein IIb/IIIa receptor inhibitors168
11.8.Aspirin (acetylsalicylic acid)168
11.9.Aspirin plus low-dose coumarins170
11.10.Clopidogrel vs aspirin171
11.11.Clopidogrel plus aspirin172
11.12.Clopidogrel and interaction with PPIs177
11.13.Rebound phenomena and resistance178
11.14.Measurement of platelet reactivity – A treatment advisor?179
11.15.Vorapaxar – The PAR-1 receptor antagonist180
11.16.Ticagrelor in secondary prevention – The PEGASUS-TIMI 54 study181
11.17.Duration of DAPT?182
11.18.Current guidelines182
11.19.Summary184
11.20.References185
12.Anticoagulants190
12.1.The Sixty Plus study in the elderly190
12.2.The WARIS-1 study190
12.3.The ASPECT-1 study190
12.4.The ASPECT-2 study191
12.5.The WARIS-2 study191
12.6.The APRICOT-2 study191
12.7.Indications for coumarins today191
12.8.Antithrombotic treatment in AF192
12.9.A new era for anticoagulation in AF194
12.10.Apixaban vs aspirin in AF – The AVERROES study199
12.11.Dabigatran in mechanical heart valves – The RE-ALIGN study200
12.12.Duration of triple therapy?200
12.13.VKA plus aggregation inhibitors in stable CAD and AF?201
12.14.Bridging in AF with LMWH – Yes or no?201
12.15.Current guidelines202
12.16.Summary203
12.17.References204
13.Antihypertensive Agents207
13.1.Hypertension and risk in CAD207
13.2.The HOPE study207
13.3.Isolated systolic hypertension (ISH)208
13.4.The INVEST study208
13.5.The VALUE study209
13.6.The EUROPA study209
13.7.Which combination therapy – The ACCOMPLISH study210
13.8.Blood pressure after ACS212
13.9.Effects of sodium reduction212
13.10.Target blood pressure values in CAD – The guidelines212
13.11.Summary214
13.12.References215
14.Omega-3 Fatty Acids218
14.1.The GISSI Prevention study218
14.2.The OMEGA study219
14.3.Conclusion219
14.4.Current guidelines219
14.5.Summary220
14.6.References220
15.Ivabradine, the If Channel Blocker221
15.1.Heart rate and risk in CAD221
15.2.Ivabradine and effects on symptoms 221
15.3.Ivabradine and effects on prognosis 221
15.4.Indications for ivabradine (EMA 2015)224
15.5.Current guidelines225
15.6.Summary225
15.7.References226
16.UA/NSTEMI = NSTE-ACS228
16.1.Definition228
16.2.Diagnosis of ACS (UA/NSTEMI/STEMI)228
16.3.The prognosis in UA/NSTEMI230
16.4.Aims of treatment231
16.5.Nitrates in UA/NSTEMI231
16.6.Beta-blockers231
16.7.Calcium antagonists231
16.8.Aspirin232
16.9.Heparin in unstable angina / NSTEMI232
16.10.Pentasaccharides233
16.11.Bivalirudin233
16.12.GP IIb/IIIa inhibitors in UA/NSTEMI234
16.13.Clopidogrel plus aspirin in UA/NSTEMI236
16.14.Prasugrel vs clopidogrel239
16.15.Ticagrelor in ACS244
16.16.Statins in acute coronary syndrome247
16.17.Invasive vs non-invasive approach in UA/NSTEMI249
16.18.The importance of GP IIb/IIIa inhibitors in PCI252
16.19.Improvement in prognosis in NSTE-ACS253
16.20.Timings during treatment of NSTEMI-ACS253
16.21.The GRACE risk score254
16.22.Current UA/NSTEMI guidelines255
16.23.Summary257
16.24.References259
17.The Treatment of Acute Myocardial Infarction (STEMI)264
17.1.The effect of thrombolysis264
17.2.Aspirin267
17.3.Clopidogrel268
17.4.Prasugrel vs clopidogrel in STEMI – The TRITON-TIMI 38 study270
17.5.Ticagrelor vs clopidogrel in STEMI patients – The PLATO study270
17.6.Anticoagulant agents271
17.7.Nitrates273
17.8.Beta-blockers275
17.9.ACE inhibitors / AT1 receptor blockers / aldosterone-receptor blockers276
17.10.Calcium antagonists278
17.11.Antiarrhythmics (lidocaine prophylaxis)278
17.12.PTCA in acute infarction (STEMI)278
17.13.Lysis vs transport to a PCI centre279
17.14.PTCA vs PTCA plus stent280
17.15.PCI plus stent plus GP IIb/IIIa inhibitor280
17.16.Aim in STEMI treatment: Primary PCI!281
17.17.DES vs BMS in STEMI282
17.18.National differences in the hospitalisation time282
17.19.The prognosis in STEMI282
17.20.The new classification of infarction283
17.21.Dual antiplatelet therapy (DAPT) plus new oral anticoagulants (NOACs)?283
17.22.Thrombus aspiration during STEMI 285
17.23.Intra-aortic balloon pump (IABP) counterpulsation285
17.24.Current STEMI guidelines286
17.25.Preventative angioplasty in STEMI?288
17.26.Summary289
17.27.References290
18.Revascularisation Procedures in Stable CAD296
18.1.Bypass surgery296
18.2.PTCA298
18.3.Stents299
18.4.PTCA/PCI vs CABG303
18.5.PTCA vs atherectomy306
18.6.Transmyocardial laser revascularisation307
18.7.Beta-blockers before CABG307
18.8.FFR measurement307
18.9.CABG in CAD and LVEF £35% – The STICH study309
18.10.Adherence to guidelines for PCI and CABG310
18.11.Measures in refractory angina311
18.12.CABG vs minimally invasive surgery 312
18.13.The current guidelines313
18.14.Summary315
18.15.References316
19.Stable CAD: Conservative Therapy vs Interventional/Surgical Therapy321
19.1.Current secondary prevention and targets in stable CAD321
19.2.Additive effects with four secondary prevention agents?322
19.3.Individual conservative measures in chronic stable CAD vs PCI325
19.4.Optimised secondary prevention vs PCI with stent326
19.5.Is late reperfusion worthwhile? The open artery hypothesis328
19.6.Intensive medical therapy vs prompt revascularisation in diabetics with stable CAD329
19.7.Meta-analyses on optimised secondary prevention vs PCI330
19.8.FFR and OMT vs OMT – The FAME II study332
19.9.Routine vs quantitative coronary angiography334
19.10.No successes with low risk334
19.11.Conservative vs interventional/surgical therapy336
19.12.The problem and a suggested solution336
19.13.COURAGE and Wall Street – A controversial subject336
19.14.Prioritising before rationing340
19.15.Guidelines for chronic stable CAD340
19.16.Summary341
19.17.References342
20.Therapy in Postinfarction Failure346
20.1.Pathophysiological background346
20.2.Spironolactone in NYHA class III and IV346
20.3.Eplerenone in NYHA II – The EMPHASIS-HF study346
20.4.Eplerenone after acute myocardial infarction with LV dysfunction347
20.5.Eplerenone in acute STEMI without heart failure?348
20.6.Stem cells in chronic ischaemic cardiomyopathy349
20.7.Beta-blockers in heart failure and AF349
20.8.The STITCH substudy on surgical ventricle reconstruction349
20.9.A new strategy: Angiotensin receptor neprilysin inhibitor (ARNI)349
20.10.Guidelines351
20.11.Summary353
20.12.References354
21.Antiarrhythmic Drugs356
21.1.Pathophysiological background356
21.2.The pro-arrhythmogenic effect in relation to the ejection fraction356
21.3.Clinical studies in ventricular extrasystoles356
21.4.Amiodarone in heart failure357
21.5.Amiodarone in post-infarct patients357
21.6.Antiarrhythmics in AF358
21.7.Does digoxin increase mortality in atrial fibrillation?364
21.8.Vernakalant365
21.9.Short-term vs long-term antiarrhythmic therapy after cardioversion for AF365
21.10.Catheter ablation in AF365
21.11.Current guidelines365
21.12.Summary366
21.13.References367
22.ICD, CRT, Cardiac Pacemakers, Implantable AF Recorder, IABP370
22.1.The implantable defibrillator (ICD)370
22.2.Cardiac resynchronisation therapy (CRT)377
22.3.Programmed stimulation for risk identification383
22.4.Cardiac pacemaker therapy384
22.5.Implantable cardiac recorder for AF detection385
22.6.Intra-aortic balloon counterpulsation (IABP)385
22.7.Summary386
22.8.References387
23.Lifestyle, Body Weight, Smoking, Alcohol, Physical Activity and Rehabilitation391
23.1.Diet391
23.2.Normalisation of body weight393
23.3.Smoking397
23.4.Alcohol400
23.5.Physical activity and rehabilitation403
23.6.When should lifestyle changes begin?405
23.7.Sex hormones (oestrogens/testosterone) in prevention?406
23.8.Multivitamins and minerals?406
23.9.Dark chocolate406
23.10.Guidelines on lifestyle407
23.11.Summary407
23.12.References409
24.Abbreviations414
Index418