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Pharmacologic Therapy of Coronary Disease Importance of Pharmacologic Approach · Diffuse Nature of Coronary Artery Disease 1. Diffuse Nature of CAD Interventional therapy targets only a focal manifestation of systemic disorder. Atherosclerosis is a diffuse disease. In ACS besides the culprit lesion, there are other active ulcerating atherosclerotic plaques liable to thrombose and produce coronary occlusion. The diffuse distribution of hemodynamically insignificant lesions with characteristics of vulnerability (atherosclerotic plaques with thin fibrous cap, a large lipid core, many inflammatory cells and few smooth muscle cells) which are liable to rupture suggests that the ideal approach of CAD is a systemic treatment which is invariably a pharmacologic approach. 2. Systemic Procoagulant and Proinflammatory State In patients with CAD particularly in ACS there is evidence of associated procoagulant and systemic inflammatory states. The degree of inflammation correlates with disease severity. Elevation in the levels of coagulation and inflammatory markers is found in patients with ACS. Variations in the degree of severity of systemic procoagulant and proinflammatory states may explain the heterogeneous nature of ACS and that this change in the internal milieu can predispose to widespread plaque degeneration and/or accelerated subsequent thrombus formation. Pharmacological treatment addressing these procoagulant and proinflammatory states is a logical approach. 3. Addressing Atherosclerosis in Other Areas While coronary interventions are limited to the focal coronary stenotic lesions, drug therapy can also address atherosclerotic disease in other arteries namely carotid, cerebral and peripheral, which is a common association with CAD (Figure 2-1). Figure 2-1: Source: Ness J etal. J Am Geriator Soc 1999. 4. Atherosclerotic Plaque Passivation and Stabilization ACS result from rupture, fissuring or erosion of an atherosclerotic plaque complicated by superimposed thrombus when exposing the subendothelial matrix and/or the strongly thrombogenic lipid core to the blood stream. Most of the ruptured plaques are of the vulnerable, unstable type. Drug therapy can stabilize these plaques and make them less prone to rupture through change in the plaque composition (decreasing and hardening of the lipid core) and interfering with the local and systemic inflammatory states that destabilize the plaque by releasing proteolytic enzymes (matrix metalloproteinses MMP) from inflammatory cells. These enzymes digest the fibrous collagenous cap of the plaque leading to its thining. Also drug therapy can improve vascular endothelial function, decreasing pressure and stress on the plaque cap and preventing or attenuating thrombus formation. Pharmacological approaches could prevent the transition of stable to unstable lesions. 5. Patients not Candidates for Revascularization Some CAD patients are not suitable for PCI or bypass surgery (CABG) because one or more of the following:Unsuitable anatomy, such as diffuse coronary disease. Very impaired left ventricular function particularly in patients with previous CABG or PCI. Extracardiac diseases, for example diabetes, cerebrovascular or peripheral vascular disease, or renal failure, which increases periprocedural morbidity and mortality. Age, often in combination with other factors. In these patients pharmacologic therapy is the only choice. 6. Persistent Symptoms After PCI or CABG A good portion of patients undergoing PCI or CABG do not achieve complete revascularization, and many of these patients continue to experience recurrent anginal symptoms or myocardial ischemia. Aggressive and maximal medical therapy is the first available approach. 7. Availability In contrast to interventional therapy which requires highly trained personnel and specially equipped hospitals and laboratories, drug therapy can be provided at home, in the ambulance and emergency room by a well-informed physician. 8. Risks The pharmacologic approach in the hands of a knowledgeable and experienced practitioner entails minimal risk to the patient with the possible exception of some side effects of drugs. 9. Proven Efficacy Drug therapy proved effective in ameliorating myocardial ischemia, delaying or preventing the progression of coronary disease, decreasing cardiac morbidity and prolonging life (see next section). 10. Costs Although many of the new drugs are expensive, the pharmacologic approach is less expensive than interventional procedures. PCI with coronary stenting is expensive approach which may not be affordable by the majority of patients in developing countries. M. MOHSEN IBRAHIM, MD Prof. of Cardiology- Cairo University President of the Egyptian Hypertension Society |
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