BACKGROUND: The CYP2C19*2 polymorphism is significantly associated with residual platelet reactivity (RPR) and maybe a major confounding factor in studies evaluating pharmacological interactions with clopidogrel. OBJECTIVES: We sought to evaluate the influence of a proton pump inhibitor (PPI), pantoprazole, indicated as relatively less influent than other PPIs, on the antiplatelet effect of clopidogrel, considering a stratification of the population for the presence of cytochrome 2C19*2 polymorphism. METHODS:105 patients with ST elevation myocardial infarction (STEMI), treated withpercutaneous coronary angioplasty (PCI) and who received dual antiplatelet therapy, were randomized between pantoprazole (n=54) or ranitidine (n=51). RPR was evaluated by Platelet Function Analyzer-100 (PFA-100) with collagen-epinephrine (CEPI) and collagene-ADP (CADP) cartridges and by light transmitted aggregometry with 10 μM adenosin diphosphate (ADP) and 1mM arachidonic acid (AA), on 5 (T0) and 30 (T1) days after PCI. RESULTS: Demographic, clinical and procedural data and the prevalence of CYP2C19*2 polymorphism were similar between the two groups. Not statistically differences were observed for CEPI-CT and for the maximal aggregation (MA) values with AA stimulus at both times. We observed a significant increase in MA values with ADP in PPI group at T0 (p=0.01) and T1 (p=0.03). At the multiple regression analysis PPI use remained significantly associated with ADP-MA both at T0 (p=0.05) and T1 (p=0.03). CONCLUSIONS: This is the first documentation in a randomized trial, after correction for the bias of CYP2C19*2 polymorphism, that pantoprazole increases the ADP-MA in patients treated with dual antiplatelet therapy.
RCT Entities:
BACKGROUND: The CYP2C19*2 polymorphism is significantly associated with residual platelet reactivity (RPR) and maybe a major confounding factor in studies evaluating pharmacological interactions with clopidogrel. OBJECTIVES: We sought to evaluate the influence of a proton pump inhibitor (PPI), pantoprazole, indicated as relatively less influent than other PPIs, on the antiplatelet effect of clopidogrel, considering a stratification of the population for the presence of cytochrome 2C19*2 polymorphism. METHODS: 105 patients with ST elevation myocardial infarction (STEMI), treated with percutaneous coronary angioplasty (PCI) and who received dual antiplatelet therapy, were randomized between pantoprazole (n=54) or ranitidine (n=51). RPR was evaluated by Platelet Function Analyzer-100 (PFA-100) with collagen-epinephrine (CEPI) and collagene-ADP (CADP) cartridges and by light transmitted aggregometry with 10 μM adenosin diphosphate (ADP) and 1mM arachidonic acid (AA), on 5 (T0) and 30 (T1) days after PCI. RESULTS: Demographic, clinical and procedural data and the prevalence of CYP2C19*2 polymorphism were similar between the two groups. Not statistically differences were observed for CEPI-CT and for the maximal aggregation (MA) values with AA stimulus at both times. We observed a significant increase in MA values with ADP in PPI group at T0 (p=0.01) and T1 (p=0.03). At the multiple regression analysis PPI use remained significantly associated with ADP-MA both at T0 (p=0.05) and T1 (p=0.03). CONCLUSIONS: This is the first documentation in a randomized trial, after correction for the bias of CYP2C19*2 polymorphism, that pantoprazole increases the ADP-MA in patients treated with dual antiplatelet therapy.
Authors: Razvan I Radu; Tuvia Ben Gal; Magdy Abdelhamid; Elena-Laura Antohi; Marianna Adamo; Andrew P Ambrosy; Oliviana Geavlete; Yuri Lopatin; Alexander Lyon; Oscar Miro; Marco Metra; John Parissis; Sean P Collins; Stefan D Anker; Ovidiu Chioncel Journal: ESC Heart Fail Date: 2021-10-19