Abstract 94: Brief Discontinuation of Proton Pump Inhibitor Therapy Enhances Anti-Platelet Effects of Clopidogrel

Background: It has been suggested that proton pump inhibitor (PPI) administration may decrease clinical efficacy of clopidogrel. We have studied changes in platelet reactivity during brief discontinuation of chronic PPI administration in patients on clopidogrel maintenance therapy. Methods: Study was approved by institutional IRB and informed consent was obtained in all patients. Study population consisted of 9 outpatients (6 females, 68+/-6 years old) on chronic clopidogrel and PPI therapy. VerifyNow P2Y12 point of care assay was used to measure P2Y12 platelet reactivity unit (PRU) and percent platelet inhibition. Platelet reactivity was measured on PPI therapy, 10 days after stopping PPI, and 10 days after re-starting PPI. Control baseline platelet reactivity testing was conducted on each occasion and remained unchanged (on enrollment 321+/-44 PRU vs. off clopidogrel 327+/-33 PRU vs. on clopidogrel 342+/-36, p=0.159). Repeated measurements ANOVA analysis was used to study overall changes in platelet reactivity. Fisher’s protected least significance difference intervals test was used to compare individual groups. All tests were 2-tailed, p<0.05 was considered significant. Results: We observed a significant reduction in platelet reactivity after PPI discontinuation (baseline PRU 205+/-111 vs. PRU 159+/-116 on day 10 post last PPI dose, p=0.028). Resuming PPI resulted in increased platelet reactivity (228+/-94 PRU after 10 days of PPI, p=0.002). Accordingly, PPI discontinuation was associated with significantly enhanced platelet inhibition (baseline percent inhibition 38+/-31 vs. 52+/-33% on day 10 after stopping PPI, p=0.029). Re-starting PPI resulted in significantly less effective platelet inhibition (percent inhibition 34+/-23% 10 days after PPI resumption, p=0.009). There were no significant differences in platelet reactivity (p=0.243) and percent inhibition (p=0.596) when baseline values were compared with ones obtained after 10 days of PPI treatment. Conclusions: We have documented dynamic changes in clopidogrel induced platelet inhibition associated with discontinuation and resumption of PPI therapy. Clopidogrel appears to provide significantly less effective platelet inhibition when PPI is administered simultaneously.