Effects of PPIs and an H2 blocker on the Antiplatelet Function of Clopidogrel in Japanese Patients under Dual Antiplatelet Therapy

Yamane, Keiichiro; Kato, Yoshihiro; Tazaki, Junichi; Tada, Takeshi; Makiyama, Takeru; Imai, Michitaka; Jinnai, Toshikazu; Ikeda, Tomoyuki; Shirakawa, Ryutaro; Kimura, Takeshi; Horiuchi, Hisanori

doi:10.5551/jat.11601

Cited by 27 publications

(20 citation statements)

References 30 publications

(29 reference statements)

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“…Accordingly, some studies showed that omeprazole attenuates the antiplatelet effect of clopidogrel [13][14][15] but others did not confirm these findings [19,20] . In contrast, esomeprazole, lansoprazole, pantoprazole and rabeprazole did not affect platelet function in patients treated with clopidogrel [13,15,[19][20][21][22] . However, it is unclear whether these ex vivo findings have clinical importance, i.e., if the co-administration of clopidogrel with omeprazole or other PPIs will result in reduced protection against cardiovascular events.…”

Section: Introductionmentioning

confidence: 74%

Clinical relevance of clopidogrel-proton pump inhibitors interaction

Bouziana

Τζιόμαλος

2015

WJGPT

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Clopidogrel is a widely used antiplatelet agent for the secondary prevention of cardiovascular events in patients with stable coronary heart disease, acute coronary syndromes and ischemic stroke. Even though clopidogrel is safer than aspirin in terms of risk for gastrointestinal (GI) bleeding, the elderly, and patients with a history of prior GI bleeding, with Helicobacter pylori infection or those who are also treated with aspirin, anticoagulants, corticosteroids or nonsteroidal antiinflammatory drugs are at high risk for GI complications when treated with clopidogrel. Accordingly, proton pump inhibitors are frequently administered in combination with clopidogrel to reduce the risk for GI bleeding. Nevertheless, pharmacodynamic studies suggest that omeprazole might attenuate the antiplatelet effect of clopidogrel. However, in observational studies, this interaction does not appear to translate into increased cardiovascular risk in patients treated with this combination. Moreover, in the only randomized, double-blind study that assessed the cardiovascular implications of combining clopidogrel and omeprazole, patients treated with clopidogrel/ omeprazole combination had reduced risk for GI events and similar risk for cardiovascular events than patients treated with clopidogrel and placebo. However, the premature interruption of the study and the lack of power analysis in terms of the cardiovascular endpoint do not allow definite conclusions regarding the cardiovascular safety of clopidogrel/omeprazole combination. Other proton pump inhibitors do not appear to interact with clopidogrel. Nevertheless, given the limitations of existing observational and interventional studies, the decision to administer proton pump inhibitors to patients treated with clopidogrel should be individualized based on the patient's bleeding and cardiovascular risk. Core tip: Even though pharmacodynamic studies suggest that omeprazole can attenuate the antiplatelet effect of clopidogrel, this interaction does not appear to translate into increased cardiovascular risk in patients treated with this combination in observational studies. In the only randomized, double-blind, placebo-controlled study that assessed the cardiovascular implications of combining clopidogrel and omeprazole, patients treated with clopidogrel/omeprazole combination had reduced risk for MINIREVIEWS

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Section: Introductionmentioning

confidence: 74%

Clinical relevance of clopidogrel-proton pump inhibitors interaction

Bouziana

Τζιόμαλος

2015

WJGPT

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“…3 Theoretically, famotidine is not metabolized by CYP2C19, and our study also demonstrated that the addition of famotidine did not affect the antiplatelet effect of clopidogrel. 8 Therefore, these findings strongly suggest that omeprazole does not affect clopidogrel efficacy. The larger number of patients analyzed in this study (n=138) would support the reliability of their results more strongly than the 2 aforementioned studies.…”

Section: Editorial Ppi and Clopidogrelmentioning

confidence: 73%

“…My group also conducted a crossover study to analyze the effects of concomitant use of omeprazole or rabeprazole in 25 patients during DAPT, in which platelet reactivity was measured with the VerifyNow system. 8 We reported that patients taking omeprazole exhibited slightly higher platelet reactivity than those taking rabeprazole, and that the reactivity under rabeprazole intake was similar to that detected in control patients not taking PPI. 8 Thus, these studies suggest that omeprazole might significantly, although slightly, decreased the antiplatelet function of clopidogrel in the Japanese population.…”

Section: Editorial Ppi and Clopidogrelmentioning

confidence: 87%

Proton-Pump Inhibitors Could Be Innocent When Used Concomitantly With Clopidogrel

Horiuchi

2012

Circ J

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“…However, it is unknown whether H2RA treatment is effective for clopidogrel‐induced or dual antiplatelet drug‐induced gastric mucosal injury. In general, because most H2RAs, such as famotidine, ranitidine and nizatidine, are renally excreted and hepatic enzymes, such as CYP2C19, do not metabolize such H2RAs, no interactions with clopidogrel and H2RAs have been reported . Therefore, an H2RA may be an appropriate alternative for patients treated with clopidogrel to avoid drug–drug interaction.…”

Section: Discussionmentioning

confidence: 99%

Prevention of gastric mucosal injury induced by anti‐platelet drugs by famotidine

Uotani

Sugimoto

Nishino

et al. 2014

The Journal of Clinical Pharma

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Anti-platelet drug-induced gastric mucosal injury correlates with intragastric pH. Our aim was to investigate prophylaxis effects of famotidine, one of the representative histamine-2 receptor antagonists (H2RA), on gastric mucosal injury induced by dual therapy with low-dose aspirin and clopidogrel in relation to Helicobacter pylori (H. pylori) infection and CYP2C19 genotypes. This study was conducted for 20 healthy Japanese volunteers (10 H. pyloripositive and 10-negative subjects) with 100 mg aspirin plus 75 mg clopidogrel (AC) once-daily dosing and AC plus 20 mg famotidine twice-daily dosing (ACH). Mucosal injury was endoscopically assessed on day 3 and 7 and 24-hour intragastric pH and antiplatelet-function test was performed on day 7. Median pH in ACH was similar between CYP2C19 extensive metabolizer (EM) and intermediate metabolizer (IM)/poor metabolizer (PM) and was significantly higher in H. pylori-positive than negative subjects (P < .05). Mucosal injury with ACH significantly decreased in both day 3 and 7 compared with AC, irrespective with H. pylori and CYP2C19 genotypes (P < .05). Although antiplatelet effect of clopidogrel in EM was significantly higher than that in IM/PM, the additional famotidine did not affect the effect. Anti-platelet drug-induced gastric injury was alleviated by famotidine without attenuation of anti-platelet functions irrespective of H. pylori and CYP2C19 genotypes.

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Effects of PPIs and an H2 blocker on the Antiplatelet Function of Clopidogrel in Japanese Patients under Dual Antiplatelet Therapy

Cited by 27 publications

References 30 publications

Clinical relevance of clopidogrel-proton pump inhibitors interaction

Clinical relevance of clopidogrel-proton pump inhibitors interaction

Proton-Pump Inhibitors Could Be Innocent When Used Concomitantly With Clopidogrel

Prevention of gastric mucosal injury induced by anti‐platelet drugs by famotidine

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