Clinical Outcomes in Patients With the Concomitant Use of Clopidogrel and Proton Pump Inhibitors After Percutaneous Coronary Intervention

Harjai, Kishore J.; Shenoy, Chetan; Orshaw, Pam; Usmani, Samer; Boura, Judy; Mehta, Rajendra H.

doi:10.1161/circinterventions.110.958884

Cited by 46 publications

(54 citation statements)

References 29 publications

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“…Several professional organizations such as the American Heart Association and the American College of Gastroenterology have recommended that a proton pump inhibitor (PPI) should be used with anti-platelet therapy consisting of clopidogrel alone or clopidogrel and aspirin for gastrointestinal protection 5 . However, evidence from mechanistic studies has indicated that the anti-platelet effect of clopidogrel is reduced in the presence of PPIs because PPIs inhibit CYP2C19, an enzyme responsible for the conversion of clopidogrel to its active metabolite [6][7][8] .…”

Section: Introductionmentioning

confidence: 99%

Risk of adverse cardiovascular outcomes and all-cause mortality associated with concomitant use of clopidogrel and proton pump inhibitors in elderly patients

Mahabaleshwarkar

Yang

Datar

et al. 2013

Current Medical Research and Opinion

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Section: Introductionmentioning

confidence: 99%

Risk of adverse cardiovascular outcomes and all-cause mortality associated with concomitant use of clopidogrel and proton pump inhibitors in elderly patients

Mahabaleshwarkar

Yang

Datar

et al. 2013

Current Medical Research and Opinion

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“…10 The strongest evidence for such an interaction is between omeprazole and clopidogrel, attributed to the fact that this PPI has a high potential to inhibit the CYP2C19 isoenzyme and thus modulate conversion of clopidogrel into its active metabolite. Previously, several observational studies 10,[15][16][17][18][19][20][21][22][23][24][25][26]29,34,35 and 1 prospective randomized trial 36 found conflicting results with respect to the association between concomitant PPI and clopidogrel use and the risk of cardiovascular outcomes. In contrast to clopidogrel and another thienopyridine, prasugrel, ticagrelor is a P2Y12 inhibitor that does not require biotransformation and has no known pharmacokinetic or pharmacodynamic interaction with PPIs.…”

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confidence: 99%

“…4,10 In contrast, ticagrelor is a directly acting P2Y12 inhibitor not requiring biotransformation 12,13 and with no known interaction with PPIs. 14 In view of the ongoing debate regarding the clinical significance of the interaction between clopidogrel and PPIs, [15][16][17][18][19][20][21][22][23][24][25][26][27][28][29] we examined the relationship between PPI use and cardiovascular outcomes in patients with ACS randomized to clopidogrel or ticagrelor in a prespecified, nonrandomized subgroup analysis of the Platelet Inhibition and Patient Outcomes (PLATO) trial. 30,31 …”

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Association of Proton Pump Inhibitor Use on Cardiovascular Outcomes With Clopidogrel and Ticagrelor

et al. 2012

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on behalf of the Platelet Inhibition and Patient Outcomes (PLATO) Trial InvestigatorsBackground-The clinical significance of the interaction between clopidogrel and proton pump inhibitors (PPIs) remains unclear. Methods and Results-We examined the relationship between PPI use and 1-year cardiovascular events (cardiovascular death, myocardial infarction, or stroke) in patients with acute coronary syndrome randomized to clopidogrel or ticagrelor in a prespecified, nonrandomized subgroup analysis of the Platelet Inhibition and Patient Outcomes (PLATO) trial. The primary end point rates were higher for individuals on a PPI (nϭ6539) compared with those not on a PPI (nϭ12 060) at randomization in both the clopidogrel (13.0% versus 10.9%; adjusted hazard ratio [HR], 1.20; 95% confidence interval [CI], 1.04 -1.38) and ticagrelor (11.0% versus 9.2%; HR, 1.24; 95% CI, 1.07-1.45) groups. Patients on non-PPI gastrointestinal drugs had similar primary end point rates compared with those on a PPI (PPI versus non-PPI gastrointestinal treatment: clopidogrel, HR, 0.98; 95% CI, 0.79 -1.23; ticagrelor, HR, 0.89; 95% CI, 0.73-1.10). In contrast, patients on no gastric therapy had a significantly lower primary end point rate (PPI versus no gastrointestinal treatment: clopidogrel, HR, 1.29; 95% CI, 1.12-1.49; ticagrelor, HR, 1.30; 95% CI, 1.14 -1.49). Conclusions-The use of a PPI was independently associated with a higher rate of cardiovascular events in patients with acute coronary syndrome receiving clopidogrel. However, a similar association was observed between cardiovascular events and PPI use during ticagrelor treatment and with other non-PPI gastrointestinal treatment. Therefore, in the PLATO trial, the association between PPI use and adverse events may be due to confounding, with PPI use more of a marker for, than a cause of, higher rates of cardiovascular events. Clinical Trial Registration-http://www.clinicaltrials.gov. Unique identifier: NCT00391872. Key Words: acute coronary syndrome Ⅲ clopidogrel Ⅲ mortality Ⅲ myocardial infarction Ⅲ ticagrelor I n patients with both ST-segment and non-ST-segment elevation acute coronary syndromes (ACS), current clinical practice guidelines recommend the use of dual antiplatelet therapy with acetylsalicylic acid and P2Y12 inhibition. 1,2 Conflicting data exist regarding the potential adverse interaction between the effects on clinical events of the P2Y12 inhibitor clopidogrel and proton pump inhibitors (PPIs), whereas the importance of such an interaction with other P2Y12 inhibitors is less investigated. Clinical Perspective on p 986Several pharmacodynamic studies have shown that some PPIs reduce the inhibition of platelet aggregation achieved with clopidogrel treatment. [3][4][5][6][7][8][9][10] This phenomenon seems meContinuing medical education (CME) credit is available for this article. Go to http://cme.ahajournals.org to take the quiz. ). Relevant exclusions to trial participation included an increased risk of bleeding (eg, active bleeding, major surgery Յ30 days), clinically im...

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“…The question still remains unanswered, however, and larger studies that are adequately powered to examine outcomes such as stent thrombosis and gastrointestinal bleeding need to be conducted to fully reassure the clinician. 3 …”

Section: Discussionmentioning

confidence: 99%

Circulation: Cardiovascular Interventions Editors' Picks

2011

Circ: Cardiovascular Interventions

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Conclusions: This randomized, double-blind, placebo-controlled, crossover study demonstrates that discontinuation of clopidogrel does not result in "rebound" platelet hyperreactivity, as determined by multiple time points, assays, agonists, and agonist concentrations.Editor's Comment: The increased incidence of ischemic events including stent thrombosis and myocardial infarction has been reported following discontinuation of clopidogrel. A potential explanation for this observation has been a possible platelet hyperactive

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Clinical Outcomes in Patients With the Concomitant Use of Clopidogrel and Proton Pump Inhibitors After Percutaneous Coronary Intervention

Cited by 46 publications

References 29 publications

Risk of adverse cardiovascular outcomes and all-cause mortality associated with concomitant use of clopidogrel and proton pump inhibitors in elderly patients

Risk of adverse cardiovascular outcomes and all-cause mortality associated with concomitant use of clopidogrel and proton pump inhibitors in elderly patients

Association of Proton Pump Inhibitor Use on Cardiovascular Outcomes With Clopidogrel and Ticagrelor

Circulation: Cardiovascular Interventions Editors' Picks

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