INTRODUCTIONDual 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.

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.

OBJECTIVESThe 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.

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.

METHODSThis 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.

RESULTS

REFERENCES1) 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.

ADVERSE CARDIAC EVENTS

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

BASELINE CHARACTERISTICSThere 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.

There were 59±11 patients in the PPI group that had no medications listed at baseline orin 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.

PATIENT DEMOGRAPHICS

LIMITATIONSThere 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.

CONCLUSIONSThe 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.