Impact of Concomitant Use of Clopidogrel and Proton Pump Inhibitor on Clinical Outcome in Coronary Stented Patients: A Retrospective Study

There remains substantial controversy regarding the effect of concomitant use of clopidogrel and proton pump inhibitors (PPIs) on the clinical outcomes of patients who underwent coronary stent implantation. We examined the effect of concomitant use of clopidogrel and PPIs on the clinical outcomes after percutaneous coronary intervention (PCI) with coronary stent implantation. From our electronic medical record database, we identified 1,147 patients who had been prescribed clopidogrel (75 mg/day) between January 1, 2007 and March 31, 2011. A total of 420 patients were selected after excluding patients with cerebral infarction or carotid stenosis treated with clopidogrel, patients without coronary stent implantation, patients who were not followed by coronary angiography, and patients who discontinued clopidogrel. We stratified these patients into two groups: clopidogrel alone (n=186) and clopidogrel+PPI (n=234). For these patients, we retrospectively reviewed their electronic medical records to identify those with stent restenosis requiring treatment. Follow-up was until the first re-angiography. The primary outcome was a composite of stent thrombosis, rehospitalization for any reason, and all-cause death. The two groups did not differ significantly in the duration of follow-up; age; sex ratio; body mass index; smoking status; a history of hypertension, dyslipidemia, or diabetes; and the type of implanted stent. There were no significant differences between clopidogrel alone and clopidogrel+PPI in the rates of primary outcomes: stent thrombosis (0.54% vs 0.43%; p=1.0000), emergency hospitalization (1.61% vs 5.13%; p=0.0651), and death (4.3% vs 7.26%; p=0.2203). No significant difference was found between the two groups in the rate of stent restenosis (19.9% vs 18.9%; p=0.7090). Altogether, there was no significant difference in the total rate of these events (26.3% vs 31.2%; p=0.2819), and adjusted odds ratio for clopidogrel+PPI was 1.117 (95% confidence interval 0.703-1.780). In this study, concomitant use of a PPI was not associated with increased adverse clinical outcomes in patients treated with clopidogrel. Overall, because of the possible drug interaction between clopidogrel and PPIs through inhibition of the cytochrome P450 2C19 enzyme (CYP2C19), it would be difficult to predict adverse clinical outcomes after PCI with coronary stent implantation. In conclusion, the present results suggest that concomitant use of PPIs for gastric protection does not adversely affect the clinical outcome of patients who are receiving clopidogrel after PCI and are at increased risk of gastrointestinal complications. (Jpn J Clin Pharmacol Ther 2012; 43(6): 393-398)