Patients who received clopidogrel (Plavix, Bristol-Myers Squibb, Sanofi-Aventis) plus a proton-pump inhibitor (PPI) had a significantly higher risk of rehospitalization for MI or coronary stent placement than did patients receiving clopidogrel alone, according to a retrospective study published April 26 in the Archives of Internal Medicine.
Recent pharmacodynamic and retrospective clinical analyses have suggested that PPIs may modify the antiplatelet effects of clopidogrel, wrote lead author Karen M. Stockl, PharmD, from the clinical services department at Prescription Solutions in Irvine, Calif., and colleagues.
Additionally, in November, the FDA required a labeling change to clopidogrel to indicate that it should not be used with AstraZeneca’s PPI, omeprazole (Prilosec/Prilosec OTC) and some other acid-reducing drugs.
The researchers conducted a retrospective cohort study of persons enrolled in a multi-state health insurance plan with commercial and Medicare clients to evaluate adverse clinical outcomes in patients using clopidogrel plus a PPI compared with clopidogrel alone.
Patients who were discharged from the hospital after MI or coronary stent placement and treated with clopidogrel plus a PPI (1,033 patients) were matched 1:1 (using propensity scoring) with patients with similar cardiovascular risk factors treated with clopidogrel alone. They evaluated rehospitalizations for MI or coronary stent placement for up to 360 days. Also, they conducted a sub-analysis to study the impact of pantoprazole sodium (Protonix, Wyeth Pharmaceuticals), the most used PPI.
According to the authors, patients who received clopidogrel plus a PPI had a 93 percent higher risk of rehospitalization for MI and a 64 percent higher risk of rehospitalization for MI or coronary stent placement than did patients receiving clopidogrel alone.
Stockl and colleagues also observed that increased risk of rehospitalization for MI or coronary stent placement for the subgroup of patients receiving clopidogrel plus pantoprazole.
Based on their findings, the authors wrote that prospective clinical trials and laboratory analyses of biochemical interactions are warranted to further evaluate the potential impact of PPIs on the efficacy of clopidogrel.