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Prescribing Patterns of Proton Pump Inhibitors in Patients
Treated with Clopidogrel Post-Drug Eluting Stent Placement
Jill Cwik, PharmD1, Ashish Shah, DO2, Sarosh Bukhari, DO2, Alex Waldman,
Parag Patel, DO2,3, and M. Nagui Sabri, MD, FACC, FSCAI2,3
(1)Department of Pharmacy, (2)Department of Medicine, (3) Department of Cardiology, Advocate Lutheran General Hospital
INTRODUCTION
Dual antiplatelet therapy is a cornerstone of medical therapy for patients undergoing percutaneous
coronary intervention (PCI) for coronary artery disease to prevent stent thrombosis. ACC/AHA (2009
focused update) guidelines recommend dual antiplatelet therapy with aspirin plus a thienopyridine for
at least one year post drug-eluting stent (DES) implantation (Class IB). The current FDA approved
thienopyridines include clopidogrel, prasugrel and ticlopidine with clopidogrel being the most
commonly used thienopyridine.
BASELINE CHARACTERISTICS
RESULTS
ADVERSE CARDIAC EVENTS
There were 6 patients in the PPI group and 14 patients in the no PPI group that had limited
information documented regarding their past medical history.
The American College of Gastroenterology (ACG) and America Heart Association (AHA) recommend
prophylactic proton pump inhibitors (PPIs) in order to prevent gastrointestinal (GI) complications such
as ulceration and bleeding when patients are receiving aspirin and clopidogrel concomitantly
following an acute coronary syndrome (ACS). Although the data are limited and retrospective in
design, it has been demonstrated that there is a significant decrease in platelet aggregation when
patients are taking PPIs with clopidogrel, resulting in adverse cardiac outcomes. To date, the only
prospective trial published COGENT (The Clopidogrel and the Optimization of Gastrointestinal
Events) did not show any difference in cardiovascular and GI outcomes in patients on dual
antiplatelet therapy with aspirin and clopidogrel.
In November, the FDA published an alert regarding an interaction between clopidogrel and
omeprazole. Omeprazole inhibits CYP2C19, which is responsible for conversion of clopidogrel to its
active form. It has been shown that omeprazole reduces the conversion of clopidogrel’s active
metabolite by about 45% and reduces clopidogrel’s effects on platelets by up to 47%. With this
decrease in the effect of clopidogrel there is potential to increase rates of in stent thrombosis and
other adverse cardiac effects.
OBJECTIVES
The purpose of the study is to determine if PPIs are appropriately prescribed in patients receiving
clopidogrel following drug eluting stent (DES) implantation at Advocate Lutheran General Hospital.
The PPI currently on formulary is omeprazole and for those patients concomitantly on clopidogrel
the recommended PPI for use is pantoprazole.
The primary objectives include evaluation of the prevalence of PPI prescribed concomitantly with
clopidogrel after placement of a DES. This includes evaluation of the indication for use, timing of
PPI prescribed and the incidence of cardiac events within one year post implantation of the DES.
The secondary objectives include characterization of prescribing patterns of PPIs in patients
receiving clopidogrel and the prevalence of cardiac events post-DES placement.
LIMITATIONS
This data collection is part of a multi-center analysis to determine if there is an association with
adverse cardiac events including association with in-stent thrombosis for up to one year post-DES
placement in patients who received a PPI receiving concomitant clopidogrel therapy.
There are several limitations to this study including the lack of documentation including medications
at baseline and those patients were taking up to one year post-DES. This lack of documentation
significantly decrease the sample of patients that were ale to be included in the analysis. In addition,
a majority of the patients did not have any documentation for the indication of the PPI. Most of the
PPIs are available over the counter and the use is difficult to track. There were a large amount of
patients that were lost during the follow up period which is a limitation because the potential adverse
events would not be able to be accounted for or tracked. Lastly another limitation due to this study
being retrospective in design, patients were not able to be questioned about compliance regarding
their medication use.
METHODS
This study involved a retrospective chart review including the patients that were greater than 18
years of age and older that were prescribed clopidogrel post-DES placement at Advocate Lutheran
General Hospital beginning September 2007 until September 2008 plus a one year follow-up.
Patients were identified using the cardiology catheterization laboratory database and were included
if they had at least one DES placed during September 2007 until September 2008. There were 390
patients that were eligible and 279 that were included in this analysis. Patients that were excluded
included those that were it was not known whether they continued clopidogrel therapy for up at least
up to one year post DES placement.
PATIENT DEMOGRAPHICS
CONCLUSIONS
There were 59±11 patients in the PPI group that had no medications listed at baseline or
in the available notes for up to 1 year follow-up in Care Connection. In addition, there were 79
patients in the non-PPI group that had no available medications at baseline or follow-up.
The adverse cardiac events evaluated in this study included incidence of unstable angina, non-ST
segment elevation myocardial infarction, and restenosis. Although there were a small incidence in
cardiac events, it was a statistically significant difference in those patients prescribed a PPI
concomitantly with clopidogrel. A statistical analysis was performed to determine if there was an
association between which PPIs have a higher incidence of cardiovascular events when prescribed
concomitantly with clopidogrel and there was no statistically significant difference. Although the
sample size in this study is limited, clinicians should be more selective about which patient should be
discharged with a PPI after stent placement. It is also important to ensure the medication list is
updated and the indication for medications are appropriately documented. Indication for PPIs should
be addressed at stent implantation to determine appropriateness of continuing upon discharge.
REFERENCES
1) The American Heart Association. 2004 Heart and Stroke Statistical Update. Dallas, TX: American Heart
Association, 2004.
2) Maisel W, Laskey W. Drug-Eluting Stents. Circulation. 2007; 115:e426-e427.
3) Ong AT, Serruys PW. Drug-Eluting Stents. Presented at the Texas Heart Institute’s symposium “Current issues
in Cardiology.” Orlando, Florida, USA 2005.
4) 2009 Focused Updates: ACC/AHA Guidelines for the Management of Patients With ST-Elevation Myocardial
Infarction and ACC/AHA/SCAI Guidelines on Percutaneous Coronary Intervention. J Am Coll Cardiol.
2009;54:2205-2241
5) ACC/AHA 2007 Guideline for the Management of Patients with Unstable Angina/Non-ST-Elevation Myocardial
Infarction. J Am Coll Cardiol. 2007;50(7):e1-e162.
6) Ho MP, Maddox TM, Wang L, Fihn SD, et al. Risk of Adverse Outcomes Associated With Concomitant Use of
Clopidogrel and Proton Pump Inhibitors Following Acute Coronary Syndrome. JAMA. 2009; 301(9):937-944.
7) Juurlink DN, Gomes T, Ko DT, Szmitko PE, et al. A population-based study of the drug interaction between
proton pump inhibitors and clopidogrel. CMAJ. 2009; 180(7):713-718.
8) Gilard M, Arnaud B, Cornily JC, Gregoire LG, et al. Influence of Omeprazole on the Antiplatelet Action of
Clopidogrel Associated With Aspirin: the randomized, double-blind OCLA (Omeprazole CLopidogrel Aspirin)
study. J Am Coll Cardiol. 2008;51:256-60.