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

Uotani, Takahiro; Sugimoto, Mitsushige; Nishino, Masafumi; Ichikawa, Hitomi; Sahara, Shu; Yamade, Mihoko; Iwaizumi, Moriya; Yamada, Takanori; Osawa, Satoshi; Sugimoto, Ken; Umemura, Kazuo; Watanabe, Hiroshi; Miyajima, Hiroaki; Furuta, Takahisa

doi:10.1002/jcph.284

Cited by 4 publications

(3 citation statements)

References 42 publications

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“…Ischemic stroke patients generally need life-long use of antiplatelet or anticoagulation for secondary prevention of cardiovascular events. Aspirin is most frequently prescribed antiplatelet, which cause gastric mucosal injury [21]. Concomitant use of non-steroidal anti-inflammatory drugs (NSAID) is also common in patients with cardiovascular risk factors [22].…”

Section: Discussionmentioning

confidence: 99%

Risk of post-stroke pneumonia with proton pump inhibitors, H2 receptor antagonists and mucoprotective agents: A retrospective nationwide cohort study

Song

Kim

2019

PLoS ONE

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Stroke patients are at high risk of developing pneumonia, which is major cause of post-stroke mortality. Proton pump inhibitors and H 2 receptor antagonists are anti-ulcer drugs, which may predispose to the development of pneumonia by suppression of the gastric acid with bactericidal activity. Unlike proton pump inhibitors and H 2 receptor antagonists, mucoprotective agents have gastroprotective effects with no or less anti-acid property. We aimed to investigate effects of the acid-suppressive medications (proton pump inhibitors and H 2 receptor antagonists) and mucoprotective agents on risk for post-stroke pneumonia using the National Health Insurance Service-National Sample Cohort in Korea. This retrospective cohort study included 8,319 patients with acute ischemic stroke. Use of proton pump inhibitors, H 2 receptor antagonists, and mucoprotective agents (rebamipide, teprenone, irsogladine, ecabet, polaprezinc, sofalcone, sucralfate, and misoprostol) after stroke were determined based on the prescription records, which were treated as time-dependent variables. Primary outcome was the development of post-stroke pneumonia. During the mean follow-up period of 3.95 years after stroke, 2,035 (24.5%) patients had pneumonia. In the multivariate time-dependent Cox regression analyses (adjusted hazard ratio [95% confidence interval]), there was significantly increased risk for pneumonia with use of proton pump inhibitors (1.56 [1.24–1.96]) and H 2 receptor antagonists (1.40 [1.25–1.58]). In contrast to the proton pump inhibitors and H 2 receptor antagonists, use of mucoprotective agents did not significantly increase the risk for pneumonia (0.89 [0.78–1.01]). In conclusion, the treatment with proton pump inhibitors and H 2 receptor antagonists was associated with increased risk for pneumonia in stroke patients. Clinicians should use caution in prescribing the acid-suppressive medications for the stroke patients at great risk for pneumonia.

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Section: Discussionmentioning

confidence: 99%

Risk of post-stroke pneumonia with proton pump inhibitors, H2 receptor antagonists and mucoprotective agents: A retrospective nationwide cohort study

Song

Kim

2019

PLoS ONE

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“…Uotani et al reported that anti-platelet drug-induced gastric injury was alleviated by famotidine without attenuation of antiplatelet functions. 22 However, the sample size in their study was only 20, and the subjects were all young, healthy volunteers, not CHD patients after undergoing PCI and taking DAPT.…”

Section: Discussionmentioning

confidence: 99%

The effect of esomeprazole vs famotidine on aspirin/clopidogrel dual therapy after percutaneous coronary intervention

Wu¹,

Chen²,

Luo³

et al. 2019

Adv Clin Exp Med

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Background. Regarding drug interactions between proton pump inhibitors (PPIs) and dual antiplatelet therapy (DAPT), controversies have arisen over the possibility that PPIs may interfere with the antiplatelet effect of DAPT. However, whether this interaction is drug-specific or a class effect needs to be determined. It is not clear whether famotidine, an H2-receptor antagonist (H2RA), interacts with DAPT. Objectives. The aim of this study was to assess the impact of esomeprazole and famotidine on the efficacy of DAPT. Material and methods. The study involved 160 patients undergoing elective percutaneous coronary interventions and treated with DAPT and concomitant use of esomeprazole (40 mg/d) or famotidine (40 mg/d). Platelet reactivity was measured with adenosine diphosphate (ADP)-induced light transmittance aggregometry (LTA) and vasodilator-stimulated phosphoprotein phosphorylation-platelet reactivity index (VASP-PRI) at baseline, 14 and 30 days after applying randomized acid-suppressing agents. Results. No significance differences were observed in treatment-by-period interactions with LTA values (p = 0.298) and VASP-PRI values (p = 0.867), which suggested no carryover effect in either regimen over the 30-day treatment period. Intergroup comparisons were done between the 2 groups at 3 times, and similar findings were observed at each time (all p > 0.05). As for intragroup measurements among the separate times, significantly lower LTA and VASP-PRI values existed on day 14 for both agents (both p < 0.05). Conclusions. The antiplatelet effect of DAPT was not affected by concomitant use of esomeprazole or famotidine. These 2 agents were much less likely than CYP2C19 polymorphisms to influence aspirin/clopidogrel therapy, supporting the assertion that the pharmacodynamic interaction between aspirin/clopidogrel and acid-suppressing agents is a drug-specific rather than a class effect.

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“…The article of Martínez‐Quintana et al suggests that CYP2C19 genotype or concurrent omeprazole use does not affect outcome in PCI patients receiving clopidogrel. Uotani et al investigated the use of famotidine (which does not inhibit CYP2C19 or CYP3A isozymes) to prevent gastric mucosal injury by antiplatelet agents, suggesting that alternatives to PPIs may be useful to reduce the risk of GI bleed when using aspirin + clopidogrel. Horenstein et al notes that larger doses of clopidogrel may be indicated in patients with reduced CYP2C19 activity .…”

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confidence: 99%

The clopidogrel conundrum

Bertino¹

2014

The Journal of Clinical Pharma

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In this issue of the Journal, we feature a number of original research articles and commentaries focusing on clopidogrel.Clopidogrel was approved for use in the late 1990s. As a prodrug, it is activated by a number of drug metabolizing enzymes including enzymes showing genetic polymorphism (CYP2C19, CYP2B6) and other enzymes showing substantial intersubject variability (CYP3A isozymes) and CYP1A2. Two major pharmacologic questions have revolved around clopidogrel for years. First, do individuals possessing CYP2C19 null alleles (primarily CYP2C19 *2 and *3), resulting in reduced or lack of CYP2C19 activity exhibit less pharmacologic effect due to lack of prodrug conversion; secondly, do certain proton pump inhibitors (PPIs) such as omeprazole and esomeprazole, which auto-inhibit CYP2C19, reduce the conversion of the prodrug clopidogrel and result in reduced efficacy?Unfortunately, the literature is not clear on either of these issues. In terms of the first issue, efficacy in the face of CYP2C19 genotype, a recent review did not find strong evidence that CYP2C19 genotype makes a difference for effect modification. 1 These authors also noted that the majority of published studies which examined CYP2C19 genotype and outcome were non-randomized substudies while the only randomized trial cited found no difference in adverse outcomes in patients regardless of CYP2C19 genotype. 1 While many Clinical Pharmacologists have wished and hoped for broad application of pharmacogenomics in drug use, clopidogrel may not be the benchmark drug in this regard.Because clopidogrel is often coupled with aspirin use in patients who have undergone percutaneous coronary intervention (PCI), PPIs may be administered concurrently to reduce the risk of GI bleeding, either as a prescription or over-the-counter drug. For this issue, whether or not a significant reduction in efficacy is seen when clopidogrel is given with certain PPIs (omeprazole and esomeprazole), also shows inconclusive data concerning this drug-drug interaction. The study of Bhatt et al. 2 suggested that concurrent omeprazole with clopidogrel did not reduce efficacy significantly, however, this study was terminated early and by the author's own conclusions, the study was not powered to show a difference in efficacy with concurrent PPI use. A subsequent metaanalysis showed no effect of PPIs on clopidogrel efficacy. 3 The unclear nature of the literature has resulted in confusion among clinicians. When examining the U.S. Food and Drug Administration (FDA) approved label for Plavix 1 (clopidogrel) the label suggests that CYP2C19 poor metabolizers (black box warning) may have reduced efficacy and alternative treatment strategies should be considered. Additionally, the FDA approved label states that doses of 80 mg of omeprazole may result in reduced efficacy of clopidogrel and thus concurrent use should be avoided. 4 Interestingly, the recommended doses of Prilosec 1 (omeprazole) for all indications except for pathological hypersecretory conditions is no more than 40 mg daily. 5 T...

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

Cited by 4 publications

References 42 publications

Risk of post-stroke pneumonia with proton pump inhibitors, H2 receptor antagonists and mucoprotective agents: A retrospective nationwide cohort study

Risk of post-stroke pneumonia with proton pump inhibitors, H2 receptor antagonists and mucoprotective agents: A retrospective nationwide cohort study

The effect of esomeprazole vs famotidine on aspirin/clopidogrel dual therapy after percutaneous coronary intervention

The clopidogrel conundrum

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