الفهرس 
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Abstract
Atherothrombosis, the unhealthy coupling of atherosclerosis and thrombosis, is the most common cause of acute ischemic events. The atherosclerotic process is diffuse, generalized, and progressive, affecting multiple vascular beds. This leads to a number of clinical manifestations, the natures of which are influenced by the target organ and specific vascular bed involved. Ischaemic events related to atherothrombosis include coronary, cerebral, and peripheral arterial disease.
Disease in one vascular bed increases the risk of disease in other, a concept known as ”cross-risk” .Stroke and myocardial infarction (MI) share common risk factors and pathological mechanisms.
Antiplatelet agents have a great importance in the management of atherothrombotic syndromes, whether in acute treatment or for secondary prevention. They are classified according to the mechanism of action into: Cyclooxygenase inhibitors (Aspirin), Phosphodiesterase enzyme Inhibitors (Dipyridamole and cilostazol), ADP receptor blockers (Clopidogrel and ticlopidine), Glycoprotein IIb/IIIa antagonist (Abciximab, Eptifibatide, Tirofiban). Prostaglandin analogues (Epoprostenol).
Clopidogrel is a prodrug that needs to be metabolized by hepatic cytochrome P450 (CYP) to an active compound that specifically and irreversibly targets the platelet P2Y12 receptor for the platelet lifespan. CYP 3A4 metabolizes clopidogrel faster than other human CYP isozymes and is the most abundant CYPs in the human liver, suggesting that they are primarily responsible for in vivo clopidogrel metabolism.
Several clinical trials have evaluated the efficiency of clopidogrel as a mono or dual therapy in combination with other antiplatelet agents as treatment for percutaneous coronary intervention and acute coronary syndromes . Whereas multidrug therapy with antiplatelet drugs, lipid-lowering and glucose-lowering agents, antihypertensive drugs, and even antidepressants has been suggested as a therapeutic strategy to reduce cardiovascular risk, multiple drug prescriptions increase the risk for drug– drug interactions. This is particularly true if more than 1 agent requires significant hepatic metabolism . Clopidogrel, atorvastatin, omeprazole, and many other drugs require hepatic cytochrome P450 (CYP) metabolism. Importantly, clopidogrel–atorvastatin and clopidogrel–omeprazole drug interactions have been described that limit the ability of clopidogrel to inhibit platelet activation and aggregation processes. The inter-individual variability in amount and activity of specific type of CYP 450 may lead to the so-called resistance to clopidogrel. It has been proposed that the term ‘resistance’ should be used when a drug is unable to reach its pharmacological target, due to inability to reach it or alterations of the target. Clopidogrel resistance is multifactorial and the mechanisms responsible for the inter-individual variability are not yet clearly defined.
Several clinical trials showed that clopidogrel reduces the overall rate of thromboembolic events in patients with recent myocardial infarction, stroke, or peripheral arterial disease as compared with aspirin. However, these clinical trials focused mainly on bleeding as a major side effect of clopidogrel therapy. Some studies reported an increase in the incidence of bleeding following dual clopidogrel and aspirin treatment. Other clinical trials demonstrated that patients with clopidogrel treatment had a significantly increased requirement for platelet and red blood cell transfusions compared with the non clopidogrel recipients. Lastly, landmark studies have established the importance of clopidogrel in the treatment of non-ST and ST elevation myocardial infarction, in percutaneous coronary intervention, stroke, and peripheral arterial disease by reducing death, reinfarction, and adverse cardiac events. These trials proved these findings after accurate measurment of the benefits and risks of this valuable drug.