Efficacy and Safety of Concomitant Use of Rabeprazole during Dual-antiplatelet Therapy with Clopidogrel and Aspirin after Drug-eluting Stent Implantation: A Retrospective Cohort Study

• Published in: YAKUGAKU ZASSHI (Journal of the Pharmaceutical Society of Japan) Vol. 130; no. 12; pp. 1743 - 1750
• Main Authors: Yasu, Takeo, Ikee, Ryota, Miyasaka, Yoshiyuki, Chubachi, Hideo, Saito, Shigeru
• Format: Journal Article
• Language: Japanese
• Published: Japan Pharmaceutical Society of Japan 2010
• Subjects: 2-Pyridinylmethylsulfinylbenzimidazoles - administration & dosage; 2-Pyridinylmethylsulfinylbenzimidazoles - metabolism; Aged; Aryl Hydrocarbon Hydroxylases - genetics; Aspirin - administration & dosage; Aspirin - adverse effects; Clopidogrel; Cohort Studies; Coronary Thrombosis - etiology; Coronary Thrombosis - prevention & control; Cytochrome P-450 CYP2C19; Drug Interactions; Drug-Eluting Stents - adverse effects; Female; Gastrointestinal Hemorrhage - chemically induced; Gastrointestinal Hemorrhage - prevention & control; Humans; Male; Middle Aged; Platelet Aggregation Inhibitors - administration & dosage; Platelet Aggregation Inhibitors - adverse effects; Platelet Aggregation Inhibitors - metabolism; Polymorphism, Genetic; Proton Pump Inhibitors - administration & dosage; Rabeprazole; Retrospective Studies; Ticlopidine - administration & dosage; Ticlopidine - adverse effects; Ticlopidine - analogs & derivatives; Ticlopidine - metabolism; Treatment Outcome
• ISSN: 0031-6903; 1347-5231

After coronary stent implantation, dual-antiplatelet therapy (DAT), such as aspirin and clopidogrel, is essential to prevent stent thrombosis. Proton-pump inhibitors (PPIs) may be used to prevent gastrointestinal (GI) bleeding during DAT, but there is no evidence for the efficacy of PPIs in this setting. Because both clopidogrel and PPIs are metabolized by cytochrome P450 (CYP) 2C19, there is a possibility that, through drug interaction, PPIs diminish the antiplatelet effect of clopidogrel. In this retrospective cohort study, we evaluated the efficacy and safety of rabeprazole in patients receiving DAT of clopidogrel and aspirin after drug-eluting stent implantation. In 199 patients treated with DAT alone (control group) and 103 patients treated with rabeprazole plus DAT (rabeprazole group), we examined the incidences of GI bleeding and major adverse cardiac events (MACE) including stent thrombosis. The incidence of GI bleeding was not significantly different between the groups (hazard ratio 0.47 [95% confidence interval 0.15-1.42], P=0.18; P=0.17 in log-rank test), although no patient with severe bleeding was observed in the rabeprazole group.