Effects of Clopidogrel and Proton Pump Inhibitors on Cardiovascular Events in Patients with Type 2 Diabetes Mellitus after Drug-Eluting Stent Implantation: A Nationwide Cohort Study.

Chi-Feng Hsieh,Chun-Yen Chen,Yi-Ting Chiang,Weng-Foung Huang,Ingo Ahrens

doi:10.1371/journal.pone.0135915

Abstract

ObjectiveTo investigate whether there is an increased risk of cardiac events in diabetic patients with a combined therapy of clopidogrel (CLO) and proton pump inhibitors (PPIs) after drug-eluting stent (DES) deployment.MethodsBy using National Health Insurance Research Database, all patients who received CLO with or without PPI therapy within 90 days after undergoing DES (limus-eluting or paclitaxel-eluting stents) deployment were enrolled. Endpoints were acute coronary syndrome (ACS) and readmission for revascularization (percutaneous coronary intervention or coronary artery bypass graft surgery) after 3, 6, and 12 months.ResultsA total of 6,603 diabetic patients received LESs (5,933 in the CLO subgroup and 670 in the CLO plus PPIs subgroup), and 3,202 patients received PESs (2,923 in the CLO subgroup and 279 in the CLO plus PPIs subgroup). The patients who received CLO plus PPIs were at higher risk of ACS than those receiving CLO within 1 year after DES deployment (LESs: 6-month hazard ratio [HR] = 1.63, and 1-year HR = 1.37; PESs: 3-month HR = 1.72). Patients with a history of ACS who received CLO plus PPIs were at higher risk of ACS after LES implantation (HR = 1.55) than those in the CLO group.ConclusionIn “real-world” diabetic patients with LES deployment, the combination of PPIs and CLO is associated with higher rates of ACS after 6 months and 1 year. Even after correction for confounding factors, concomitant PPI use remained an independent predictor of cardiac events, emphasizing the clinical importance of this drug—drug interaction.

Highlights

Dual-antiplatelet therapy (DAPT) consisting of aspirin and clopidogrel (CLO) is a cornerstone in the medical treatment of acute coronary syndrome (ACS) and after percutaneous coronary intervention (PCI)
The patients who received CLO plus pump inhibitors (PPIs) were at higher risk of ACS than those receiving CLO within 1 year after drug-eluting stent (DES) deployment (LESs: 6month hazard ratio [hazard ratios (HRs)] = 1.63, and 1-year HR = 1.37; paclitaxel-eluting stents (PESs): 3-month HR = 1.72)
Patients with a history of ACS who received CLO plus PPIs were at higher risk of ACS after limus-eluting stents (LESs) implantation (HR = 1.55) than those in the CLO group

Summary

Introduction

Dual-antiplatelet therapy (DAPT) consisting of aspirin (acetylsalicylic acid [ASA]) and clopidogrel (CLO) is a cornerstone in the medical treatment of acute coronary syndrome (ACS) and after percutaneous coronary intervention (PCI). Compared with ASA alone, the combination of ASA and CLO was shown to significantly reduce the incidence of cardiovascular events after ACS. Incomplete endothelialization, which makes DESs susceptible to late stent thrombosis, is frequently observed 6–12 months after the procedure.[5] DAPT was considered to be essential after stent implantation to prevent early and late in-stent thrombosis.[6] a mono-prescription or dual-prescription antiplatelet treatment strategy is associated with an increased risk of gastrointestinal (GI) tract bleeding.[7] Proton pump inhibitors (PPIs) reduced antiplatelet-related GI tract bleeding among high-risk patients, including patients prescribed DAPT.[8] According to current US guidelines, PPIs are indicated with DAPT even in the absence of GI tract symptoms or in the presence of upper GI tract bleeding. According to current US guidelines, PPIs are indicated with DAPT even in the absence of GI tract symptoms or in the presence of upper GI tract bleeding. [8],[9]

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Conclusion