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

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.

Prevalence and Safety of Prescribing PPIs with Clopidogrel in Palestine

“…Some studies suggest that patients with cardiovascular diseases and comorbidities and being treated with chronic medications have a greater possibility that these medications may compete with or inhibit the CYP isoenzymes responsible for the bioactivation of clopidogrel. 32,33 Therefore, prescribing clopidogrel to these patients might explain why the active metabolite of clopidogrel is reduced below the needed concentration to inhibit platelet aggregation. A recent randomized crossover study conducted on 28 healthy patients also failed to show a consistent increase in cardiovascular events in patients treated with clopidogrel and PPI concurrently (pantoprazole p-value= 0.786 (SD= 0.557), omeprazole P-value= 0.653 (SD= 0.615), rabeprazole p-value= 0.726 (SD= 0.592), esomeprazole p-value= 0.807 (SD= 0.574), lansoprazole p-value= 0.887 (SD =0.592), dexlansoprazole p-value=0.998 (SD= 0.592)).…”

Proton-pump inhibitors adverse effects: a review of the evidence and position statement by the Sociedad Española de Patología Digestiva

“…During 2015, at least 5 additional sudies have been reported (142)(143)(144)(145)(146) that attempt to correlate PPI plus clopidogrel use with higher CV risk, with no conclusive findings. While observational studies suggest a PPI-clopidogrel interaction, such interaction remains clinically unidentified in randomized clinical trials (147)(148)(149).…”