Concomitant Use of Proton Pump Inhibitors and Clopidogrel Is Not Associated with Adverse Outcomes after Ischemic Stroke in Chinese Population

Abstract

Conflicting data exist as to whether proton pump inhibitors (PPIs) diminish the efficacy of clopidogrel. We, therefore, assessed the effect of concomitant PPI use in ischemic stroke (IS) patients receiving clopidogrel. We consecutively enrolled 535 IS patients receiving clopidogrel, 166 of whom were concomitantly taking PPIs. Platelet aggregation was measured before and after 7-10 days of treatment with clopidogrel. Single nucleotide polymorphisms of CYP3A4, CYP3A5, CYP2C19*2, and CYP2C19*3 were examined. The primary outcome was a composite of recurrent ischemic stroke (RIS), myocardial infarction (MI), and vascular death occurring during the 6-month follow-up. The secondary outcome was the modified Rankin Scale score at the end of follow-up. The primary outcome occurred in 45 patients and the frequency did not differ in patients with or without PPI treatment. The percentage inhibition of platelet aggregation and the frequency of clopidogrel resistance were similar between patients treated with or without PPIs after clopidogrel treatment. However, for patients carrying a reduced-function CYP2C19*2 (AG/AA genotype) or CYP3A5 (GG/AG genotype), the inhibition of platelet aggregation was significantly lower in patients treated with PPIs. Cox regression analysis showed that diabetes mellitus, clopidogrel resistance, CYP2C19*2 AG/AA genotype, and patients carrying two loss-of-function variant alleles were independent risk factors for the primary outcome, but not the use of PPIs. The concomitant use of PPIs and clopidogrel in patients with IS may not be associated with an increased risk of RIS, MI, or vascular death. Further well-designed randomized controlled studies are necessary to confirm our current results.