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Clinical Significance of the Clopidogrel-Proton Pump Inhibitor Interaction After Peripheral Endovascular Intervention
Andrew J. Meltzer, M.D., Priscilla Da Silva, Francesco A. Aiello, M.D., James F. McKinsey, M.D., Darren B. Schneider, M.D., Gautam V. Shrikhande, M.D..
New York-Presbyterian Hospital, New York, NY, USA.

OBJECTIVES:
The impact of proton pump inhibitor (PPI) administration on the antiplatelet effect of clopidogrel remains controversial. Studies suggest that mechanistic interactions between these medications may lead to higher rates of adverse cardiac events after myocardial infarction or coronary intervention. The objective of this study is to evaluate the effects of concurrent PPI and clopidogrel administration on outcomes after peripheral endovascular interventions.
METHODS:
Retrospective review of a prospectively maintained database identified patients undergoing angioplasty and stenting (PTA+S) of the superficial femoral artery (SFA) for lifestyle-limiting claudication. Patients with critical limb ischemia, multilevel disease, and those undergoing atherectomy or angioplasty without stenting were excluded. Medical record review confirmed post-intervention administration of clopidogrel and identified patients concurrently prescribed a PPI. Univariate analyses (Wilcoxon, chi-square) were performed to compare demographics, lesion characteristics, complication rates, and outcome measures. Patency comparisons were made with Cox-PH multivariable models and Kaplan-Meier function.
RESULTS:
109 limbs were treated in 103 patients. All were prescribed clopidogrel for one month; concurrent PPI use (+PPI) was identified after 42 (38.5%) interventions. Compared to -PPI patients, +PPI patients had no statistically significant differences in demographics, co-morbidity prevalence (including diabetes, renal insufficiency, heart failure, coronary disease, or smoking status), lesion length, degree of stenosis, or runoff. There were no cases of immediate thrombosis in either group. There were more early failures in +PPI patients, with reduced 6-month (87.7+/-5.8%vs.96.3+/-2.6%) and 1-year (74.2+/-7.9%vs.90.2+/-4.2%) primary patency. Throughout follow-up there were more instances of patency loss (50% vs. 42%) in +PPI patients, and a trend towards reduced primary patency among +PPI, although this did not achieve statistical significance (P = 0.45). By multivariate analysis of risk factors for patency loss as well as PPI status, only chronic occlusion was an independent predictor of primary patency loss (P = .023;HR:1.54[95% CI:1.1 - 2.3]).
CONCLUSIONS:
The clinical significance of the clopidogrel-PPI interaction is a controversial topic that has been the subject of numerous studies in the cardiology literature. This is the first report to examine this medication interaction after peripheral intervention. Results are notable for a trend towards more early failures and reduced patency in patients prescribed clopidogrel and PPIs. Further studies are needed to clarify this phenomenon, particularly given the high prevalence of PPI use at the time of intervention.


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