Relation of Proton Pump Inhibitor Use After Percutaneous Coronary Intervention With Drug-Eluting Stents to Outcomes

Gaglia, Michael A.; Torguson, Rebecca; Hanna, Nicholas; González, Manuel A.; Collins, Sara D.; Syed, Asmir I.; Ben‐Dor, Itsik; Maluenda, Gabriel; Delhaye, Cédric; Wakabayashi, Kohei; Zhang, Xue; Suddath, William O.; Kent, Kenneth M.; Satler, Lowell F.; Pichard, Augusto D.; Waksman, Ron

doi:10.1016/j.amjcard.2009.10.063

Cited by 70 publications

(60 citation statements)

References 27 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…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.…”

mentioning

confidence: 99%

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

et al. 2012

View full text Add to dashboard Cite

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...

show abstract

mentioning

confidence: 99%

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

et al. 2012

View full text Add to dashboard Cite

show abstract

“…Yasuda et al (22) have previously demonstrated that combination therapy with DAPT and PPI decreases the effect of DAPT; however, the combination therapy was shown to decrease the risk of recurrent hemorrhage. Moreover, previous studies (23)(24)(25)(26) have also demonstrated that combination therapy with PPI and clopidogrel reduced the antiplatelet effect of clopidogrel. Therefore, whether combination therapy with clopidogrel and PPI is reasonable remains controversial, and further clinical trials are required.…”

Section: Discussionmentioning

confidence: 99%

Clinical outcomes of various continued antiplatelet therapies in patients who were administered DAPT following the implantation of drug-eluting stents and developed gastrointestinal hemorrhage

Guo

Wei

2016

Experimental and Therapeutic Medicine

View full text Add to dashboard Cite

Abstract. Although an increasing number of patients accept dual antiplatelet therapy (DAPT) following implantation of drug-eluting stents (DES) for coronary heart disease (CHD), the proportion of patients with DAPT who subsequently develop gastrointestinal hemorrhage continues to increase. To ensure the clinical outcomes from DES, it is important to formulate a novel continued antiplatelet therapy for patients who were administered DAPT and subsequently develop gastrointestinal hemorrhage following DES implantation. The present study aimed to evaluate the effects of continued aspirin, clopidogrel or DAPT use on the incidence of clinical adverse events and gastrointestinal rebleeding in patients who received DAPT and subsequently developed gastrointestinal hemorrhage following implantation of DES for CHD. Between 2004 and 2010, 108 consecutive patients receiving DAPT developed gastrointestinal hemorrhage following DES implantation for CHD at Liuzhou General Hospital (Liuzhou, Guangxi). These patients were divided into three groups according to the novel antiplatelet therapy. The occurrence of major adverse cardiac events (MACE), including cardiac death, non-fatal myocardial infarction, heart failure or target vessel revascularization, net adverse clinical events (NACE), including major bleeding, stroke or MACE, and gastrointestinal rebleeding during clinical follow-up following the initial procedure were compared among these three groups. The results of this analysis demonstrated that the occurrence rate of MACE, NECE and gastrointestinal rebleeding was not significantly different among these groups (P>0.05). Furthermore, survival analysis was performed and although the survival curves of MACE and NECE were not significantly different among these groups, gastrointestinal rebleeding was demonstrated to be significantly different among the three groups (P<0.05), and continued aspirin or clopidogrel use was superior to continued DAPT. In conclusion, the results of the present study indicated that there were no significant differences in the clinical effectiveness and safety of continuing antiplatelet monotherapy or DAPT in patients who are administered DAPT and experience gastrointestinal hemorrhage following DES implantation. As for the prevention of recurrent bleeding, antiplatelet monotherapy was demonstrated to be superior to DAPT. Moreover, the treatment of patients who are administered DAPT and experience gastrointestinal hemorrhage following DES implantation must involve an evaluation of the risk of complications, including stent thrombosis, continuous bleeding and recurrent hemorrhage.

show abstract

“…[12][13][14]24 Proton pump inhibitors, or at least those with greater affinity for the CYP2C19 enzyme (e.g., omeprazole), may increase the risk for adverse events, but only in a subset of patients. For example, it is conceivable that individuals with a CYP2C19*17 allele and the ultrarapid metabolizer phenotype, which encompasses approximately 40% of Caucasians and 45% of African-Americans (but < 5% of Asians), are somewhat protected from adverse clinical consequences of concomitant PPI and clopidogrel use.…”

mentioning

confidence: 99%

“…In fact, several observational and case-control studies, including the study by Dr. Rolf Kreutz and his colleagues published in this issue of Pharmacotherapy, have shown an increased risk for major adverse cardiovascular events with concomitant clopidogrel and PPI therapy versus clopidogrel therapy without a PPI. 12-14, 19, 20 Omeprazole, lansoprazole, and esomeprazole were the primary PPIs used in three of the studies [12][13][14] ; the fourth study did not provide data on specific PPI use. 19 In the study by Dr. Kreutz and his colleagues, omeprazole, esomeprazole, and pantoprazole were the most commonly used PPIs, followed by lansoprazole and rabeprazole.…”

mentioning

confidence: 99%

“…10 Among patients treated with both clopidogrel and aspirin, 20-64% also receive PPI therapy. [11][12][13][14] Clopidogrel is a prodrug that requires biotransformation through a two-step process to its pharmacologically active thiol metabolite. This metabolite irreversibly inhibits the platelet P2Y 12 adenosine 5′-diphosphate receptor, thus preventing platelet aggregation.…”

mentioning

confidence: 99%

See 1 more Smart Citation

Clopidogrel and Proton Pump Inhibitors: Between a Rock and a Hard Place

Momary

Cavallari

2010

Pharmacotherapy

View full text Add to dashboard Cite

Relation of Proton Pump Inhibitor Use After Percutaneous Coronary Intervention With Drug-Eluting Stents to Outcomes

Cited by 70 publications

References 27 publications

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

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

Clinical outcomes of various continued antiplatelet therapies in patients who were administered DAPT following the implantation of drug-eluting stents and developed gastrointestinal hemorrhage

Clopidogrel and Proton Pump Inhibitors: Between a Rock and a Hard Place

Contact Info

Product

Resources

About