Pharmacologic Therapy of Coronary Disease

M. MOHSEN IBRAHIM, MD
Prof. of Cardiology- Cairo University
President of the Egyptian Hypertension Society

Introduction

 Coronary artery disease (CAD) is possibly the leading cause of cardiological consultations, and is predicted to be the main reason for disability worldwide by the year 2020. The prognosis of patients with CAD has improved significantly over the past two decades, thanks to introduction of interventional techniques and the development of effective drug therapy. This book will review only the pharmacological approach, and how to achieve the maximal benefit out of medical therapy to improve the patient outcome. The main objectives are to orient both the practitioner and consultant with modern drug therapy in this rapidly growing and challenging field.

For a number of reasons writing about drug therapy of coronary artery disease, is not an easy job.

First: current interest for the majority of cardiologists is the interventional namely catheter approach. They would like to know more about new types of stents rather than about new antithrombotics. There is both a conscious and subconscious bias against drug therapy that will minimize the failures of interventions and underestimates the success of drugs.

Second: the potential efficacy of new drugs is often neglected and at the same time how to make the best use of the old ones is not known. Update information in the pharmacological field is rarely appreciated. This lack of knowledge underscores the current trend of cardiologists and practitioners to follow an invasive approach even in situations proved that drug therapy or a more conservative policy can do the same if not a better job. Despite the advances in pharmacotherapy, it is not uncommon to refer patients for coronary angiography and interventions without trying optimal medical therapy. Drugs when used properly can be very effective therapeutic weapons.  

Third: information in the area of pharmacological therapy is rapidly growing. New drugs are introduced and many are undergoing clinical trials. The progress is so fast to the extent that by the time the book is printed many issues may be outdated and newer approaches are developed. Therapeutic policies based upon new trials will necessitate changes in practice guidelines over short period. Management of CAD is becoming a rapidly moving target.

 This monograph will try to define the role of modern medical therapy in the face of overwhelming enthusiasm for invasive procedures.

Acknowledgement

 The author acknowledges the efforts made by Dr. Ghada Sayed for the Cardiology Department, Cairo University and her valuable help in the final editing of the book. Also, the excellent secretarial assistance of Mrs. Rehab Mohamed, who helped in editing and typing is very much appreciated.

Table of CONTENTS 

 PART I:  PHARMACOLOGIC THERAPY VERSUS CORONARY INTERVENTION

 Chapter 1: Limitations of Coronary Interventions ................................................. P 

Chapter 2:  Importance of Pharmacologic Approach ................................................P

Chapter 3: Evaluation of Therapeutic Efficacy..........................................................P

Chapter 4: Results of Clinical Trials ......................................................................... P

Chapter 5: Chronic Stable Angina (non-acute coronary artery disease) ..................P

Chapter 6: Acute Coronary Syndromes ..................................................................... P

PART II: ANTI-ISCHEMIC DRUGS

Chapter 7: Nitrates ..................................................................................................... P

Chapter 8: Beta-adrenergic Blockers ......................................................................... P

Chapter 9: Calcium Antagonists................................................................................... P

Chapter 10: Metabolic Anti-anginal Drugs ................................................................. P

Chapter 11: Selective Heart Rate-Lowering Agents................................................... P

PART III: ANTIPLATELET AGENTS

Chapter 12: Structure and Function of Blood Platelets ................................................ P

Chapter 13: Aspirin ..........................................................................................................P

Chapter 14: Thienopyridines. Ticlopidine and Clopidogrel............................................ P

Chapter 15: Glycoprotein IIb/IIIa Antagonists ..............................................................P

PART IV: ANTITHROMBOTICS, ANTICOAGULANTS AND FIBRINOLYTICS

Chapter 16: Blood Coagulation and Fibrinolytic System ............................................... P

Chapter 17: Antithombotic Agents- Heparin....................................................................P

Chapter 18: Direct Thrombin Inhibitors .......................................................................... P

Chapter 19: Oral Anticoagulants ...................................................................................... P

Chapter 20: Fibrinolytic Agents ........................................................................................ P

PART V: RENIN-ANGIOTENSIN-SYSTEM BLOCKADE

Chapter 21: Main Components of RAS and Actions of Angiotensin II ....................................................... P

Chapter 22: Pharmacologic Blockade of RAS and its Rationale in Coronary Artery Disease .................. P

Chapter 23: RAS Blockade in Coronary Artery Disease .............................................................................. P

 PART VI: LIPID LOWERING DRUGS

Chapter 24: Fat and Lipoprotein Metabolism......................................................................P

Chapter 25: Statins ............................................................................................................... P

Chapter 26: Other Lipid Lowering Agents .......................................................................... P

• Nicotinic Acid.
• Fibric Acid Derivatives.
• Bile Acid Sequestrants.
• New Agents.

   Part I

Pharmacologic Therapy Versus Coronary Interventions

 "The aim of argument, or of discussion, should not be victory …. but progress"

Joseph Joubert

Chapter 1: Limitations of Coronary Interventions

Chapter 2:  Importance of Pharmacologic Approach

Chapter 3: Evaluation of Therapeutic Efficacy

Chapter 4: Results of Clinical Trials

Chapter 5: Chronic Stable Angina (non-acute coronary artery disease)

Chapter 6: Acute Coronary Syndromes

  Chapter (1)

Limitations of Coronary Interventions

• Limitations of Coronary Angiography
• Limitations of PCI

Enthusiasm for the catheter intervention techniques makes cardiologists ignore the limitations of this approach. It is becoming a common practice to do coronary angiograms for every patient with chest pain and to perform percutaneous catheter intervention (PCI) for all patients with acute coronary syndromes (ACS) without considering the shortcomings of this policy.

Limitations are of two types:

1. Limitations of coronary artery imaging through angiography.
2. Limitations of PCI.

1.       Limitations of Coronary Angioraphy

 A.      Estimation of Stenosis Severity

 There are a number of reasons to doubt the accuracy of estimating the degree of stenosis through angiography:

1. There is a disagreement between angiographers when coming to assessment of the severity of coronary stenosis, an observer variability up to 50% is reported.
2. Coronary stenosis is assessed by being compared to a reference segment presumed to be normal. The reference segment is frequently diseased because of the diffuse nature of coronary atherosclerosis. This will lead to underestimation of degree of stenosis.
3. In ACS the presence of intraluminal thrombus will contribute to the severity of stenosis. Resolution of the thrombus will decrease the assessed severity.
4. Complex coronary lesions after plaque rupture are difficult to assess.
5. Positive coronary remodeling is common in atherosclerotic coronary arteries where there is outward displacement of the external elastic membrane by the atherosclerotic plaque. There is minimal or no encroachment on coronary artery lumen. The atherosclerotic plaque protrudes in the wall outside the lumen
   (Fig 1-1). Coronary angiography will miss the atherosclerotic plaque and shows normal lumen.

B.      Stenosis Significance   

Coronary angiography is of limited value in defining the significance of coronary stenosis.

1. Plaque composition and morphology which is more important than the degree of stenosis can not be defined by angiography. Acute coronary syndromes (unstable angina, myocardial infarction and sudden death) are often due to rupture of plaques with less than 50 percent stenosis.
2. The impact of coronary anatomy as assessed by angiography does not many times reflect the actual physiology detected by perfusion imaging which is the usual main concern. There is discordance between severity of coronary stenosis and physiologic effect.

2.       Limitations of PCI

1. Targeting only severe lesions, whereas most myocardial infarctions develop from hemodynamically insignificant lesions.
2. Diffuse nature of coronary atherosclerosis. Multiple vulnerable plaques (atherosclerotic plaques which are liable to rupture and precipitate ACS) are present in sites other than the culprit lesion in ACS.
3. Embolization of thrombi and atherosclerotic material following catheter interventions in ACS will block microvasculature leading to no reflow and myocyte necrosis.
4. Restenosis rate inspite of stenting varies from 10 to 30 percent.
5. Costs; PCI particularly with coronary stenting is an expensive procedure.
6. Risks; arterial injury, coronary dissection and hematoma.

 Figure (1-1): A large ASO plaque in the wall of coronary artery growing away from the coronary artery lumen producing external or reversed remodeling. There is no encroachment on the lumen which looks normal in spite of the large