Effects of pantoprazole and esomeprazole on platelet inhibition by clopidogrel

Siller‐Matula, Jolanta M.; Spiel, Alexander; Lang, Irene M.; Kreiner, Gerhard; Christ, Guenter; Jilma, Bernd

doi:10.1016/j.ahj.2008.09.017

Cited by 330 publications

(261 citation statements)

References 31 publications

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“…3 This was further demonstrated by Siller-Matula et al, where the use of pantoprazole and esomeprazole was not associated with an impaired response to clopidogrel. 17 In a prospective, randomized trial, Cuisset et al found that patients on clopidogrel and pantoprazole had significantly lower VASP-PRI 1 month after treatment compared with patients on clopidogrel and omeprazole. There were also significantly more clopidogrel nonresponders in the omeprazole group.…”

Section: Discussionmentioning

confidence: 99%

Recurrence of Acute Myocardial Infarction in Patients Discharged on Clopidogrel and a Proton Pump Inhibitor After Stent Placement for Acute Myocardial Infarction

Evanchan¹,

Donnally²,

Binkley³

et al. 2010

Clinical Cardiology

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Background: The purpose of this study was to determine the readmission rate for acute myocardial infarction (AMI) in patients discharged on clopidogrel and a proton-pump inhibitor (PPI) versus patients discharged on clopidogrel alone after experiencing an AMI and undergoing stent placement. Clopidogrel is a prodrug that requires metabolism in the liver by the cytochrome P450 system (CYP450), in particular cytochrome P450 2C19 (CYP2C19).1 Recent studies have suggested that medications metabolized by CYP450, such as PPIs, influence the effect of clopidogrel on platelet function 2,3 with an increased risk of cardiovascular events. 4,5 PPIs are often administered with clopidogrel due to the increased bleeding risk of dual antiplatelet therapy, a strategy endorsed by existing consensus guidelines.6Hypothesis: Treatment with a PPI in combination with clopidogrel would increase the risk of readmission for an AMI after stent placement for AMI. Methods: We collected data on all patients discharged on clopidogrel after stent placement for an AMI between January 2003 and January 2008. Patients were followed for 1 year after their index hospitalization for readmission for an AMI. Rates of readmission were determined for those discharged on clopidogrel alone versus those discharged on clopidogrel and a PPI.Results: Patients discharged on clopidogrel and a PPI had higher rates of readmission for AMI within 1 year of stent implantation for AMI. Conclusions: Patients discharged on clopidogrel and a PPI, including esomeprazole and pantoprazole, seem to be at an increased risk of recurrent AMI within 1 year after stent placement for an AMI. IntroductionClopidogrel is a prodrug that is metabolized to its active metabolite by the cytochrome P450 enzyme system. Protom pump inhibitors (PPIs) are frequently prescribed in combination with clopidogrel to help reduce the risk of gastrointestinal bleeding. Several recent studies have suggested that many PPIs, especially those that undergo extensive metabolism by the cytochrome P450 2C19 system such as omeprazole, may diminish the antiplatelet effects and clinical effectiveness of clopidogrel. In contrast, other reports have not found any association between the use of PPIs in combination with clopidogrel and an increased risk of adverse cardiovascular outcomes. Therefore, we sought to assess the association between PPI and clopidogrel combination therapy after stent placement for an AMI and recurrent AMI.

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Section: Discussionmentioning

confidence: 99%

Recurrence of Acute Myocardial Infarction in Patients Discharged on Clopidogrel and a Proton Pump Inhibitor After Stent Placement for Acute Myocardial Infarction

Evanchan¹,

Donnally²,

Binkley³

et al. 2010

Clinical Cardiology

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“…All PPIs are metabolized, to a greater or lesser degree, by isoenzymes of CYP P450, and therefore may have differing potentials for interaction with clopidogrel. Omeprazole, lansoprazole, pantoprazole and rabeprazole have been studied in detail [4], and pantoprazole [5] and ezomeprazole [6] may have less effect on clopidogrel via this pathway.…”

mentioning

confidence: 99%

Clopidogrel and proton pump inhibitors: can near patient testing help in the tailoring of dual antiplatelet prescription?

Amoah

Worrall

Smallwood

et al. 2010

Journal of Thrombosis and Haemostasis

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“…52 Compared with placebo, omeprazole but not pantoprazole or esomeprazole appears to reduce the antiplatelet effect of clopidogrel. 53,54 However, preliminary unpublished data were reported in May 2009 that suggested that there may be a class effect in the interaction of clopidogrel with PPIs: omeprazole, lansoprazole, esomeprazole, and pantoprazole use was associated with an increased risk of major adverse cardiac events over 12 months, compared with patients who did not have a PPI pharmacy claim. 55 This conclusion was derived from an analysis of pharmacy and medical claims in the Medco Solutions database for 9,862 patients who received a PPI, compared with 6,828 patients who did not receive a PPI following a percutaneous coronary intervention (PCI).…”

Section: Clinical Profile Of Prasugrelmentioning

confidence: 99%

Review of Prasugrel for the Secondary Prevention of Atherothrombosis

Spinler

Rees²

2009

JMCP

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BACKGROUND: The role of platelets in atherothrombotic disease is well established, and antiplatelet therapy is now recommended for the shortand long-term management of patients with acute coronary syndromes (ACS), with and without percutaneous coronary intervention (PCI). The thienopyridine clopidogrel is accepted as a key component of antiplatelet management and is recommended in current treatment guidelines as addon therapy to aspirin in secondary prevention to reduce coronary risk in patients with ACS and/or following PCI. The FDA Cardiovascular and Renal Drugs Advisory Committee met on February 3, 2009, and recommended approval of prasugrel, but with guidance to physicians about increased risk in low-weight or elderly patients and avoidance of use (a) around coronary artery bypass graft (CABG) or other surgical or invasive procedures and (b) in patients with prior or current stroke or transient ischemic attack (TIA).OBJECTIVE: To review the published literature examining primarily the clinical efficacy and safety of prasugrel in ACS patients.METHODS: The PubMed database was searched for English language studies involving the use of prasugrel in human subjects published up to April 2009 using the keyword "prasugrel." The review focused on randomized, controlled trials with clinical end points. Abstracts from recent scientific meetings (up to November 2008) were also searched for relevant studies, as was the FDA briefing document prepared in advance of the advisory committee meeting on February 3, 2009. RESULTS: Of the 124 published papers identified, 28 pertained to research in human subjects: 21 on prasugrel pharmacology and 7 with clinical end points. In the Prasugrel in Comparison to Clopidogrel for Inhibition of Platelet Activation and Aggregation-Thrombolysis in Myocardial Infarction (PRINCIPLE-TIMI) 44 trial, a cross-over study of laboratory-determined platelet activity, prasugrel produced significantly greater inhibition of platelet aggregation than clopidogrel after both loading dose (74.8% vs. 31.8% at 6 hours, P < 0.001) and maintenance dose (day 14: 61.3% vs. 46.1%, P < 0.001) in patients with stable coronary artery disease (CAD). In the only end point outcomes study (Trial to Assess Improvement in Therapeutic Outcomes by Optimizing Platelet Inhibition with Prasugrel-Thrombolysis in Myocardial Infarction [TRITON-TIMI 38]) there was a significant reduction in adverse cardiac outcomes in patients with ACS treated with prasugrel, 94% of whom received at least 1 coronary stent. The incidence of the primary composite end point of cardiovascular death, nonfatal MI, or nonfatal stroke was 9.9% in the prasugrel group versus 12.1% in the clopidogrel group (hazard ratio = 0.81, 95% CI = 0.73-0.90, P < 0.001). However, the risk of a major bleeding event was significantly greater with prasugrel versus clopidogrel, and prasugrel appeared to be of net clinical harm in patients with a history of stroke/TIA. The FDA reviewer recommended that prasugrel use be discouraged in patients aged 75 years or older o...

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Effects of pantoprazole and esomeprazole on platelet inhibition by clopidogrel

Cited by 330 publications

References 31 publications

Recurrence of Acute Myocardial Infarction in Patients Discharged on Clopidogrel and a Proton Pump Inhibitor After Stent Placement for Acute Myocardial Infarction

Recurrence of Acute Myocardial Infarction in Patients Discharged on Clopidogrel and a Proton Pump Inhibitor After Stent Placement for Acute Myocardial Infarction

Clopidogrel and proton pump inhibitors: can near patient testing help in the tailoring of dual antiplatelet prescription?

Review of Prasugrel for the Secondary Prevention of Atherothrombosis

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