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Patients with peripheral arterial disease (PAD) typically demonstrate multivessel disease and may also exhibit coronary artery disease. Individuals with PAD, whether symptomatic or asymptomatic are at an increased risk for cardiovascular mortality. Antiplatelet therapy along with risk factor reduction is the hallmark treatment to reduce cardiovascular events in patients with PAD (Patti, Micieli, Cimminiello, & Bolognese, 2020). Clopidogrel, also known as Plavix, is approved for the prevention of atherosclerotic events associated with PAD (Whalen, 2018).
Clopidogrel is a prodrug, which is absorbed in the intestine and activated in the liver. 85% of the drug is hydrolyzed by esterases into an inactive compound, leaving only 15% available for hepatic metabolism. CYP 2C19 participates in oxidative steps to convert clopidogrel into its active metabolite (Wang et al., 2015). Clopidogrel inhibits the binding of ADP to the P2Y12 receptor on platelets, blocking their ability to bind to fibrinogen and to each other, irreversibly. Maximum inhibition of platelet aggregates is achieved in 3-5 days. For quicker effect, oral loading doses may be required. Due to metabolism by CYP 2C19, genetic polymorphism can lead to a decreased clinical response in patients who are poor metabolizers. Tests are available to identify poor metabolizers, as other antiplatelet drugs would be more appropriate in this case (Whalen, 2018). Drugs that inhibit CYP 2C19, such as omeprazole and esomeprazole should be avoided as they can decrease the anti-thrombotic effect of clopidogrel. However, it is important to note that other proton pump inhibitors like, pantoprazole or raberprazole do not affect the pharmacokinetics of clopidogrel (Wang et al., 2015). Furthermore, there is an increase risk of bleeding when clopidogrel is taken with NSAIDs, warfarin, SSRIs and SNRIs (Carter, & Felicilda Reynaldo, 2020).
The most serious adverse effect of using clopidogrel is prolonged bleeding, for which there is no antidote (Whalen, 2018). Other adverse reactions include, epistaxis, hematuria, bruising, rash, hypersensitivity, thrombotic thrombocytopenic purpura (TTP), acute liver failure, angioedema and agranulocytosis. Common side effects include pruritis, purpura, diarrhea and rash (Carter, & Felicilda Reynaldo, 2020). Although there is no lab monitoring that is required for clopidogrel, unlike warfarin, nurses should report signs of TTP, hemolytic anemia, neurologic changes, renal dysfunction and fever immediately.
