FIBRINOLYTIC THERAPY IN CLINICAL PRACTICE; ED. BY FREEK VERHEUGT

This book is a practical guideline in the clinical application of fibrinolytic therapy in a variety of life-threatening disorders. It is not an encyclopedia for all trials in mostly evidence-based treatment options. It is meant for physicians taking care of acute ill patients either at intensive care units, coronary care units or emergency departments. Bioscience & Clinical Medicine Book Cover 1 Half-Title 2 Title 3 Copyright 4 Contents 6 Contributors 7 Preface 10 1 Pharmacology of thrombolytic agents 11 Introduction 11 Physicochemical properties of thrombolytic agents 11 t-PA and variants 11 u-PA moieties 15 Streptokinase and derivatives 15 Staphylokinase and derivatives 16 Mechanism of action of thrombolytic agents 16 t-PA and variants 16 u-PA moieties 17 Streptokinase and derivatives 17 Staphylokinase and derivatives 18 Pharmacodynamics of thrombolytic agents 18 t-PA and variants 18 u-PA moieties 21 Streptokinase and derivatives 21 Staphylokinase and derivatives 22 Conclusions 23 References 24 2 General principles of fibrinolytic therapy in acute myocardial infarction 29 Introduction 29 Clinical opportunities 30 Restoring vessel patency 30 Clinical trials of thrombolysis 32 General comments 32 Adding aspirin 32 Improving treatment schedules 33 The search for simpler treatment schedules: bolus thrombolytics 34 Reteplase (r-PA) 34 Lanoteplase (n-PA) 36 Tenecteplase (TNK-rt-PA) 36 Summary of bolus thrombolytic therapy 37 Vessel patency and microvascular perfusion 37 Problems with thrombolytics 38 Stroke 38 Bleeding 39 Anaphylaxis 39 Failed thrombolysis and ‘rescue’ 39 After thrombolysis, then what? 40 Patient selection for thrombolytic therapy 41 Clinical guidelines and treatment schedules 41 Concluding comments 42 References 44 3 Antiplatelet therapy 48 Introduction 48 Pathogenesis 48 Acute phase of myocardial infarction 51 Aspirin 51 Ticlopidine and clopidogrel 53 Ridogrel 53 GP llb/llla antagonists 53 Chronic phase of myocardial infarction 62 Aspirin 62 Monotherapy alone 62 Monotherapy vs anticoagulation therapy 62 Monotherapy vs combination therapy 63 Clopidogrel 64 Oral GP llb/llla antagonists 65 References 65 4 Anticoagulants as adjunctive therapy in fibrinolysis for acute myocardial infarction 70 Introduction 70 Antithrombin therapy in fibrinolysis 70 Oral anticoagulation after myocardial infarction (Table 4.3) 73 Conclusions 77 References 78 5 Pharmacological interventions for acute myocardial infarction 80 Introduction 80 Beta blockers 81 Angiotensin-converting enzyme (ACE) inhibitors 83 Calcium channel blockers 84 Nifedipine 85 Recommendations 85 Diltiazem 86 Recommendations 86 Verapamil 86 Recommendations 87 Magnesium 87 Nitrates 88 Lipid lowering drugs 89 Adenosine 90 Glucose-insulin-potassium (GIK) 91 Improvement of microvascular function 91 Platelets 92 Neutrophils 92 Complement inhibition 93 Oxygen free radicals 93 Calcium 93 References 93 6 Percutaneous coronary intervention in acute ST-segment elevation of myocardial infarction 100 Angioplasty vs fibrinolytic therapy 100 Percutaneous transluminal coronary angioplasty (PTCA) 102 Cardiogenic shock 104 Stenting vs balloon angioplasty 106 Conclusion 110 References 110 7 Pre-hospital fibrinolytic therapy 113 Time is muscle—and muscle is life 113 Treatment delay in clinical practice, and the need for pre-hospital triage and therapy 115 Randomized trials of pre-hospital vs in-hospital fibrinolysis 118 Benefits and risks in pre-hospital fibrinolysis 122 Pre-hospital fibrinolysis: the Dutch experience 125 Fibrinolysis or primary angioplasty? 128 References 129 8 Fibrinolytic therapy in venous thromboembolism 133 Introduction 133 Deep vein thrombosis (DVT) 133 Background: epidemiology, natural history and prognosis 133 Anticoagulant therapy: heparin and vitamin K antagonists 134 Fibrinolytic therapy 134 Catheter-directed fibrinolytic therapy 135 Pulmonary embolism 138 Background: epidemiology, natural history and prognosis 138 Anticoagulant treatment: heparin and vitamin K antagonists 139 Fibrinolytic therapy 139 Efficacy of fibrinolytic therapy: surrogate markers 139 Efficacy of fibrinolytic therapy: clinical outcomes 140 Safety bleedings 142 Massive pulmonary embolism 142 Right ventricular dysfunction 146 Dose regimen 146 Summary: practical guidelines 147 References 148 9 General principles of fibrinolytic therapy in ischaemic stroke 152 Introduction 152 Initial patient assessment 152 Intravenous thrombolysis for acute ischaemic stroke 153 The streptokinase trials 153 The rt-PA trials 153 NINDS 154 ECASS I 154 ECASS II 155 ATLANTIS 155 Meta-analyses 156 Phase IV trials of intravenous thrombolysis and cost aspects 157 Intra-arterial thrombolysis for acute ischaemic stroke 163 PROACT I 164 PROACT II 164 Diagnostic imaging and thrombolytic therapy 165 Conclusion, recommendations and future prospects 167 References 168 Index 174 Book Cover......Page 1 Half-Title......Page 2 Title......Page 3 Copyright......Page 4 Contents......Page 6 Contributors......Page 7 Preface......Page 10 t-PA and variants......Page 11 Streptokinase and derivatives......Page 15 t-PA and variants......Page 16 Streptokinase and derivatives......Page 17 t-PA and variants......Page 18 Streptokinase and derivatives......Page 21 Staphylokinase and derivatives......Page 22 Conclusions......Page 23 References......Page 24 Introduction......Page 29 Restoring vessel patency......Page 30 Adding aspirin......Page 32 Improving treatment schedules......Page 33 Reteplase (r-PA)......Page 34 Tenecteplase (TNK-rt-PA)......Page 36 Vessel patency and microvascular perfusion......Page 37 Stroke......Page 38 Failed thrombolysis and ‘rescue’......Page 39 After thrombolysis, then what?......Page 40 Clinical guidelines and treatment schedules......Page 41 Concluding comments......Page 42 References......Page 44 Pathogenesis......Page 48 Aspirin......Page 51 GP llb/llla antagonists......Page 53 Monotherapy vs anticoagulation therapy......Page 62 Monotherapy vs combination therapy......Page 63 Clopidogrel......Page 64 References......Page 65 Antithrombin therapy in fibrinolysis......Page 70 Oral anticoagulation after myocardial infarction (Table 4.3)......Page 73 Conclusions......Page 77 References......Page 78 Introduction......Page 80 Beta blockers......Page 81 Angiotensin-converting enzyme (ACE) inhibitors......Page 83 Calcium channel blockers......Page 84 Recommendations......Page 85 Verapamil......Page 86 Magnesium......Page 87 Nitrates......Page 88 Lipid lowering drugs......Page 89 Adenosine......Page 90 Improvement of microvascular function......Page 91 Neutrophils......Page 92 References......Page 93 Angioplasty vs fibrinolytic therapy......Page 100 Percutaneous transluminal coronary angioplasty (PTCA)......Page 102 Cardiogenic shock......Page 104 Stenting vs balloon angioplasty......Page 106 References......Page 110 Time is muscle—and muscle is life......Page 113 Treatment delay in clinical practice, and the need for pre-hospital triage and therapy......Page 115 Randomized trials of pre-hospital vs in-hospital fibrinolysis......Page 118 Benefits and risks in pre-hospital fibrinolysis......Page 122 Pre-hospital fibrinolysis: the Dutch experience......Page 125 Fibrinolysis or primary angioplasty?......Page 128 References......Page 129 Background: epidemiology, natural history and prognosis......Page 133 Fibrinolytic therapy......Page 134 Catheter-directed fibrinolytic therapy......Page 135 Background: epidemiology, natural history and prognosis......Page 138 Efficacy of fibrinolytic therapy: surrogate markers......Page 139 Efficacy of fibrinolytic therapy: clinical outcomes......Page 140 Massive pulmonary embolism......Page 142 Dose regimen......Page 146 Summary: practical guidelines......Page 147 References......Page 148 Initial patient assessment......Page 152 The rt-PA trials......Page 153 ECASS I......Page 154 ATLANTIS......Page 155 Meta-analyses......Page 156 Phase IV trials of intravenous thrombolysis and cost aspects......Page 157 Intra-arterial thrombolysis for acute ischaemic stroke......Page 163 PROACT II......Page 164 Diagnostic imaging and thrombolytic therapy......Page 165 Conclusion, recommendations and future prospects......Page 167 References......Page 168 Index......Page 174 One of the major breakthroughs in the treatment of cardiovascular disease is the introduction of fibrinolytic therapy. Better knowledge of the pathogenesis of acute ischemic syndromes has identified acute thrombosis as the triggering event in most cases. Thrombosis of large and small arteries may have catastrophic consequences such as sudden death, myocardial infarction, ischemic stroke, pulmonary embolism and acute limb necrosis. Fibrinolytic therapy is aimed at early restoration of occluded blood vessels thereby improving symptoms and organ recovery, reducing infarct size and subsequently improving quantity and quality of life. However, fibrinolytic drugs have severe, sometimes fatal side-effects. These mainly consist of bleeding, sometimes fatal cerebral bleeding. Therefore, stringent patient selection is mandatory: age, time to treatment, relative and absolute contraindications and comitant medication are of utmost importance for safe and efficacious fibrinolysis. Fibrinolytic Therapy in Clinical One of the major breakthroughs in the treatment of cardiovascular disease is the introduction of fibrinolytic therapy. Better knowledge of the pathogenesis of acute ischemic syndromes has identified acute thrombosis as the triggering event in most cases. Thrombosis of large and small arteries may have catastrophic consequences as sudden death, myocardial infarction, ischemic stroke, pulmonary embolism and acute limb necrosis. Fibrinolytic therapy is aimed at early restoration of occluded blood vessels, thus improving symptoms and organ recovery, reducing infarct size and improving quantity and quality of life. However, fibrinolytic drugs have severe, sometimes fatal side-effects. These center on bleeding, sometimes fatal cerebral bleeding. Therefore, stringent patient selection is mandatory; age, time to treatment, relative and absolute contraindications and comitant medication are of utmost importance for safe and efficacious fibrinolysis A practical guide in the clinical application of fibrinolytic therapy in a variety of life-threatening disorders, this text is a guide for physicians taking care of acutely ill patients either at intensive care units, coronary care units, ambulances or emergency departments.