Clopidogrel Pharmacogenetics: A Valid Method to Assure Effectiveness and Appropriateness of the Antiplatelet Therapy - ICCAD 2017 - The 12th International Congress on Innovations in Coronary Artery Disease , 15-17 October, 2017 Venice, Italy

Valeria Conti ^1,2 Valentina Manzo ^1,2 Carmine Sellitto ^1,2 Teresa Iannaccone ^1,2 Maria Costantino ³ Graziamaria Corbi ⁴ Paola Malangone ¹ Giovanna Nicolella ⁵ Giancarlo Accarino ⁵ Amelia Filippelli ^1,2

¹Dipartimento di Medicina, Chirurgia e Odontoiatria “Scuola Medica Salernitana”, University of Salerno
²Servizio di Farmacologia Clinica e Farmacogenetica, AOU “San Giovanni di Dio e Ruggi d’Aragona”, Salerno-Italia
³F.I.R.S.Thermae, Napoli-Italia, Associazione no-profit F.I.R.S.Thermae
⁴Dipartimento di Medicina e Scienze per la Salute, University of Molise
⁵Unità di Chirurgia vascolare, AOU “San Giovanni di Dio e Ruggi D’Aragona”

Clopidogrel is an antiplatelet agent commonly administered to prevent thromboembolic events in patients with peripheral and coronary artery disease after stent placement. It is a pro-drug converted into active metabolite by hepatic cytochromes, including CYP2C19. Reduction of antiplatelet activity and increased adverse events frequently occur in patients bearing CYP2C19-*2 and -*3 polymorphisms. Moreover, the effectiveness of clopidogrel is affected by drug-drug interaction with proton pump inhibitors (mainly omeprazole) that strongly inhibit CYP2C19.

We report the cases of three men with carotid artery stenosis, on treatment with clopidogrel, aspirin and omeprazole, admitted to University Hospital of Salerno-Italy for a percutaneous transluminal angioplasty (PTA).

Compliance to treatment was assessed by Morisky Medication Adherence Scale; antiplatelet aggregation was measured by platelet function testing and clopidogrel pharmacogenetics was determined by allelic discrimination assay with Real-Time PCR.

Before PTA, the patients had an aggregation rate corresponding to a value occurring in the absence of treatment; adherence scores were very high; pharmacogenetic testing revealed the presence of CYP2C19*2 allele.

Taking into account the insufficient platelet aggregation inhibition, the presence of CYP2C19*2 allele and the inappropriate use of omeprazole, the therapy was changed by replacing omeprazole with ranitidine and by administering a supplemental dose of clopidogrel.Then, the patients repeated platelet functional testing, showing a value well suited with a therapeutic effect of clopidogrel.

Patients who do not adequately respond to clopidogrel have a 5-10 fold increased risk for stent thrombosis, whereas the regular responders’ risk is very low. This case series report emphasizes the importance of monitoring the antiplatelet therapy by pharmacological adherence assessment and platelet function testing, and underlines the role of the pharmacogenetics in assuring pharmacological appropriateness.