Concurrent clopidogrel-PPI linked to increased MI, revascularization risk
MedWire News: Patients treated with clopidogrel and a proton pump inhibitor (PPI) are at increased risk for rehospitalization for myocardial infarction (MI) or coronary stent placement, according to another observational study evaluating the potential impact of these drugs interacting.
The findings conflict with recent observational and meta-analysis findings, and available randomized data. The authors call for more prospective randomized clinical studies to examine the clinical relevance of the putative pharmacologic interaction between PPIs and clopidogrel further.
The team of US researchers studied electronic records for commercial and Medicare members enrolled in a multistate health insurance plan who had undergone MI or coronary stenting. They used propensity scoring to match 1033 patients who were treated with clopidogrel and a PPI with the same number of patients with similar cardiovascular risk factors who were treated with clopidogrel alone. The overall mean age of patients was 69.1 years.
Karen Stockl (Prescription Solutions, Irvine, California) and colleagues report in the Archives of Internal Medicine that the final matched clopidogrel plus PPI and clopidogrel alone cohorts were similar in terms of demographics and cardiovascular medical history but the clopidogrel plus PPI group had a higher mean Charlson comorbidity score (p=0.04).
Of note, the most commonly prescribed PPI in the clopidogrel plus PPI cohort was pantoprazole (63.8%), followed by rabeprazole sodium (15.4%), omeprazole (8.3%), lansoprazole (8.0%), and esomeprazole magnesium (4.5%).
Rehospitalization due to MI was significantly more frequent over the 360-day follow-up among concurrent users of clopidogrel and PPIs than those taking clopidogrel alone, at 9.7 versus 4.1 events per 100 person-years, respectively (adjusted hazard ratio [HR]=1.93, p=0.03).
The rate of rehospitalization due to MI or a coronary stent procedure was also higher in the clopidogrel plus PPI cohort, at 27.6 versus 14.3 events per 100 person-years (adjusted HR=1.64, p=0.005).
A subanalysis of the 659 patients receiving clopidogrel plus pantoprazole showed they too had a significantly higher risk for the combined endpoint of rehospitalization for MI or coronary stent placement than their matched pairs receiving clopidogrel alone (adjusted HR=1.91, p=0.008). This suggests that, contrary to previous indications, “the potential interaction between PPIs and clopidogrel is not specific to omeprazole,” remark the authors. However, they admit their finding conflicts with mechanistic data suggesting pantoprazole has low potential to impair clopidogrel activity.
The researchers conclude: “This study provides additional information supporting a potentially higher risk of adverse clinical outcomes in patients receiving clopidogrel with a PPI.
“These findings highlight the need for additional prospective randomized clinical studies to further evaluate clinical outcomes associated with a potential drug-drug interaction between clopidogrel and PPIs.”
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By Caroline Price