Proton pump inhibitors, genetic polymorphisms and response to clopidogrel therapy

2011 ◽  
Vol 105 (06) ◽  
pp. 933-944 ◽  
Author(s):  
Himawan Fernando ◽  
Anthony Dart ◽  
Karlheinz Peter ◽  
James Shaw
Keyword(s):  
Genetic Polymorphisms ◽  
Proton Pump Inhibitors ◽  
Proton Pump ◽  
Active Form ◽  
Poor Response ◽  
Current Evidence ◽  
Considerable Proportion ◽  
Gi Bleeding ◽  
Clopidogrel Therapy ◽  
Coronary Syndromes

SummaryClopidogrel has become part of the mainstay of therapy for acute coronary syndromes and in patients post stenting. Clopidogrel is a pro drug and is metabolised by liver enzymes, particularly CYP2C19, into its active form. A considerable proportion of patients have a poor response to clopidogrel and this may be due to several factors. Genetic polymorphisms involved in clopidogrel’s absorption, metabolism and activity at the platelet may interfere with its antiplatelet actions. Further, proton pump inhibitors (PPI) may interfere with clopidogrel’s actions by functionally reducing the ability of CYP2C19 to convert clopidogrel to its active metabolite. By attenuating clopidogrel’s actions, both polymorphisms and drug interactions may increase the risk of thrombotic events during clopidogrel therapy. This review will explore the current evidence relating to the association between PPIs, genetic polymorphisms and poor response to clopidogrel. Routine genetic testing cannot be recommended for patients receiving dual antiplatelet therapy (DAPT). However, it may have a role for patients with an episode of stent thrombosis, prior to planned high-risk stenting or major bleeding. Regarding concomitant clopidogrel and PPI therapy, it is recommended that only patients with previous gastrointestinal (GI) bleeding or multiple risk factors for GI bleeding should be prescribed gastroprotection. This is due to the uncertainty surrounding the clinical significance of this interaction given the discordant biochemical and clinical data, conflicting results from observational studies and the limitations of the COGENT study. Pantoprazole seems least likely to interact with clopidogrel and most suitable for use in patients receiving DAPT.

scholarly journals The Pharmacogenetics of Cytochrome P450 2C19 Enzymes - Effects on Clopidogrel and Proton Pump Inhibitors

2014 ◽  
Vol 6 (1) ◽  
pp. 33
Author(s):  
Yusmiati Yusmiati ◽  
Dewi Muliaty
Keyword(s):  
Cytochrome P450 ◽  
Proton Pump Inhibitors ◽  
Proton Pump ◽  
Platelet Reactivity ◽  
Active Form ◽  
Anti Platelet Therapy ◽  
Cytochrome P450 2C19 ◽  
Cyp2c19 Gene ◽  
Anti Platelet Drug ◽  
Clopidogrel Therapy

BACKGROUND: Cytochrome P450 (CYP) enzymes play important roles in human, including drug metabolism. CYP2 is the largest family of human CYP, with its sequence comprising almost one third of all CYP sequences, and responsible for the metabolism of approximately 2% of clinically administrated drugs. One of the most important enzymes in this family is the CYP2C19 enzyme. The CYP2C19 gene is polymorphic, and the variation is common especially in the Asian population.CONTENT: CYP2C19 is responsible for the metabolism of various drugs, including proton pump inhibitors (PPIs) such as omeprazole and lansoprazole, psychotropic drugs including diazepam and imipramine, anticonvulsants such as phenobarbital and mephenytoin. and the recently most studied the anti-platelet drug, clopidogrel, and many others. Drugs metabolized predominantly by this enzyme like clopidogrel and PPIs might be much affected by the genotype status of CYP2C19. Clopidogrel is a pro-drug requiring a group of enzymes to convert to its active form, particularly the CYP2C19. PPIs are metabolized to its inactive metabolites mainly by CYP2C19 in the liver. Some PPIs are inhibitor of CYP2C19 enzymes, and interaction of PPIs and clopidogrel has been widely studied.SUMMARY: The association of CYP2C19 genotypes with the plasma level of active clopidogrel and platelet reactivity in individual taking this drug is well-established. Although conflicting results still exist for the association of CYP2C19 genotypes to the clinical outcomes of clopidogrel therapy, this effect seems to be consistent in patients receiving clopidogrel for coronary stents. Due to the interaction of certain PPIs and clopidogrel, the use of PPIs other than omeprazole is recommended, especially for patients taking dual anti platelet therapy of clopidogrel and aspirin.KEYWORDS: pharmacogenetics, CYP2C19, proton pump inhibitors, clopidogrel

Are Proton Pump Inhibitors More Effective Than Histamine-2-Receptor Antagonists for Stress Ulcer Prophylaxis in Critically Ill Patients? A Systematic Review and Meta-Analysis of Cohort Studies

2021 ◽  
pp. 106002802110590
Author(s):  
Na He ◽  
Yingying Yan ◽  
Shan Su ◽  
Qinggang Ge ◽  
Suodi Zhai
Keyword(s):  
Systematic Review ◽  
Cohort Studies ◽  
Critically Ill ◽  
Proton Pump Inhibitors ◽  
Proton Pump ◽  
Stress Ulcer ◽  
Meta Analysis ◽  
Risk Of Bias ◽  
Gi Bleeding ◽  
Ulcer Prophylaxis

Background: Histamine-2-receptor antagonists (H2RAs) have been largely replaced by proton pump inhibitors (PPIs) for stress ulcer prophylaxis (SUP) despite the inconclusive evidence concerning comparative effectiveness. Objective: To compare the effectiveness of PPIs and H2RAs on SUP in real-world setting. Methods: PubMed, Embase, and the Cochrane Library were searched from inception to September 19, 2021. We included cohort studies comparing PPIs with H2RAs in critically ill adult patients and explicitly reporting the outcome of gastrointestinal (GI) bleeding or mortality. Newcastle-Ottawa Scale was used to assess potential risk of bias. We conducted a random-effects meta-analysis and only the studies with adjusted effect estimates were pooled. The Grading of Recommendations Assessment, Development, and Evaluation system was used to assess the overall quality of the evidence. Results: Thirteen cohort studies (N = 145 149) were eligible and 11 of them available for full texts were of low to moderate risk of bias. Meta-analysis of adjusted effect estimates indicated that PPIs were associated with a significantly higher risk of GI bleeding, compared with H2RAs (8 studies, odds ratio [OR] = 1.98, 95% confidence interval [CI] = 1.30-3.01, low certainty). Post hoc pooling analysis also suggested that PPIs were associated with a slightly higher risk of mortality in comparison with H2RAs (7 studies, OR = 1.27, 95% CI = 1.13-1.42, low certainty). Conclusion and Relevance: The systematic review of cohort studies showed that PPIs were associated with higher risks of GI bleeding and mortality, although the certainty of evidence was low. Overall, we suggest not excluding H2RAs for SUP, while further studies are essential for elucidating the risk stratification, optimal regimen, and specific duration.

scholarly journals The frequency of CYP2C19 genetic polymorphisms in Russian patients with peptic ulcers treated with proton pump inhibitors

2015 ◽  
pp. 111 ◽  
Author(s):  
Natalia Denisenko ◽  
Dmitrij Sychev ◽  
Zhanna Sizova ◽  
Andrej Grachev ◽  
Konstantin Velikolug
Keyword(s):  
Genetic Polymorphisms ◽  
Proton Pump Inhibitors ◽  
Proton Pump ◽  
Peptic Ulcers

scholarly journals Long-term use of proton-pump inhibitors and risk of gastric cancer: a review of the current evidence

2019 ◽  
Vol 12 ◽  
pp. 175628481983451 ◽  
Author(s):  
Ka Shing Cheung ◽  
Wai K. Leung
Keyword(s):  
Gastric Cancer ◽  
Proton Pump Inhibitors ◽  
Proton Pump ◽  
Randomized Clinical Trials ◽  
Bacterial Overgrowth ◽  
Current Evidence ◽  
Neoplastic Progression ◽  
Increased Risk ◽  
H Pylori

Gastric cancer remains one of the leading cancers in the world with a high mortality, particularly in East Asia. Helicobacter pylori infection accounts for the majority of the noncardia gastric cancers by triggering gastric inflammation and subsequent neoplastic progression. Eradication of H. pylori can reduce, but not totally eliminate, subsequent risk of developing gastric cancer. Proton-pump inhibitors (PPIs) are one of the most widely prescribed medications worldwide. With their profound gastric-acid suppression, there are concerns about a possible carcinogenic role in gastric cancer, due to induced hypergastrinemia, gastric atrophy and bacterial overgrowth in the stomach. While randomized clinical trials to establish causality between long-term PPI use and gastric cancer are lacking, current evidence based on observational studies suggests PPIs are associated with an increased gastric cancer risk. However, opinions on causality remain divergent due to unmeasured and possible residual confounding in various studies. Our recent study has showed that even after H. pylori eradication, long-term PPI use is still associated with an increased risk of gastric cancer by more than twofold. Hence, long-term PPIs should be used judiciously after considering individual’s risk–benefit profile, particularly among those with history of H. pylori infection. Further well-designed prospective studies are warranted to confirm the potential role of PPIs in gastric cancer according to baseline gastric histology and its interaction with other chemopreventive agents like aspirin, statins and metformin.

Proton Pump Inhibitors and Dabigatran Therapy: Impact on Gastric Bleeding and Dabigatran Plasma Levels

2019 ◽  
Vol 45 (08) ◽  
pp. 846-850 ◽  
Author(s):  
Tomáš Bolek ◽  
Matej Samoš ◽  
Ingrid Škorňová ◽  
Peter Galajda ◽  
Ján Staško ◽  
...  
Keyword(s):  
Proton Pump Inhibitors ◽  
Proton Pump ◽  
Plasma Levels ◽  
Thrombin Inhibitor ◽  
Gi Bleeding ◽  
Gastric Bleeding ◽  
Increased Risk ◽  
The Impact ◽  
Dabigatran Therapy

AbstractDabigatran etexilate, a direct thrombin inhibitor, is now frequently used for long-term pharmacological prevention of stroke or systemic embolism in patients with atrial fibrillation. However, such long-term dabigatran therapy (DT) significantly increases the risk of upper gastrointestinal (GI) bleeding. This increased risk of gastric bleeds might be reduced with gastroprotective agents, such as proton pump inhibitors (PPIs). PPIs coadministrated with dabigatran reduce the risk of upper GI bleeding in patients on long-term oral DT. Nevertheless, there is heated discussion regarding interactions between PPI and dabigatran that lead to decreases in dabigatran plasma levels. This article reviews up to date data about the risk of gastric bleeding on dabigatran, the impact of PPI on the reduction of gastric bleeding, and the interaction between PPI and dabigatran leading to decreased dabigatran plasma levels.

Intravenous Proton-Pump Inhibitors versus H2-Antagonists for Treatment of GI Bleeding

2003 ◽  
Vol 37 (3) ◽  
pp. 433-437 ◽  
Author(s):  
Rebecca M Huggins ◽  
Ann C Scates ◽  
Joanne K Latour
Keyword(s):  
Proton Pump Inhibitors ◽  
Proton Pump ◽  
Ph Control ◽  
Outcome Data ◽  
High Dose ◽  
Gi Bleeding ◽  
Receptor Antagonists ◽  
Medline Search ◽  
Upper Gi ◽  
Clinical Literature

OBJECTIVE: To evaluate the evidence supporting the use of intravenous proton-pump inhibitors in the treatment of gastrointestinal (GI) hemorrhage in comparison with histamine2 (H2)-receptor antagonists. DATA SOURCES: Clinical literature was accessed through a MEDLINE search (1966–October 2002). Data from abstracts and fully published articles were retrieved for analysis. Key search terms included pantoprazole, omeprazole, proton-pump inhibitors, gastrointestinal hemorrhage, histamine2-receptor antagonists, ranitidine, and cimetidine. DATA SYNTHESIS: There are limited published clinical outcome data evaluating the use of intravenous pantoprazole in patients with upper GI hemorrhage. However, there are several gastric pH studies suggesting that intravenous pantoprazole is effective in quickly obtaining and maintaining a pH >6. When considering the results from studies of high-dose intravenous omeprazole, in addition to the pantoprazole data, the relative efficacy of intravenous proton-pump inhibitors appears to be superior to that of intravenous H2-receptor antagonists in providing a more predictable and sustained pH control. CONCLUSIONS: Intravenous proton-pump inhibitors are suitable, possibly superior, alternatives to intravenous H2-receptor antagonists in treatment of upper GI bleeding.

scholarly journals Clinical Outcomes of Concomitant Use of Proton Pump Inhibitors and Dual Antiplatelet Therapy: A Systematic Review and Meta-Analysis

2021 ◽  
Vol 12 ◽  
Author(s):  
Hongzhou Guo ◽  
Zhishuai Ye ◽  
Rongchong Huang
Keyword(s):  
Antiplatelet Therapy ◽  
Proton Pump Inhibitors ◽  
Proton Pump ◽  
Cardiovascular Events ◽  
Observational Studies ◽  
Dual Antiplatelet Therapy ◽  
Meta Analysis ◽  
Gi Bleeding ◽  
Coronary Syndrome ◽  
All Cause Mortality

Background: The safety and efficacy associated with the use of proton pump inhibitors (PPIs) by patients with coronary artery disease receiving dual antiplatelet therapy (DAPT) remain unclear.Methods: The evaluated outcomes included combined major adverse cardiovascular events (MACEs), myocardial infarction (MI), all-cause mortality, and gastrointestinal (GI) bleeding. A random effects meta-analysis, stratified by study design, was performed and heterogeneity was assessed using the I2 statistic.Results: In total, 6 randomized controlled trials (RCTs) (6930 patients) and 16 observational studies (183,546 patients) were included. Analysis of RCTs showed that there were no significant differences in the incidences of MACEs (risk ratio [RR] = 0.89 [95% confidence interval (CI) = 0.75–1.05]), MI (RR = 0.93 [95% CI = 0.76–1.15]), and all-cause mortality (RR = 0.79 [95% CI = 0.50–1.23]) in the PPI groups vs. the non-PPI groups. Pooled data from observational studies revealed an inconsistent association between the use of each PPI subtype and the increased risks of MACEs during clopidogrel treatment. There was no increased risk of MACEs or all-cause mortality associated with the use of PPIs (as a class) and other P2Y12 inhibitors. Both the RCTs and observational studies revealed that the use of PPIs significantly reduced the risks of GI bleeding.Conclusion: The use of PPIs was associated with a reduced risk of GI bleeding in patients treated with DAPT after percutaneous coronary intervention or acute coronary syndrome. There was no clear evidence of an association between the use of PPIs and adverse cardiovascular events.Clinical Trial Registration: identifier [CRD42020190315]

scholarly journals Proton Pump Inhibitors and Fracture Risk: A Review of Current Evidence and Mechanisms Involved

2019 ◽  
Vol 16 (9) ◽  
pp. 1571 ◽  
Author(s):  
Benjamin Ka Seng Thong ◽  
Soelaiman Ima-Nirwana ◽  
Kok-Yong Chin
Keyword(s):  
Fracture Risk ◽  
Proton Pump Inhibitors ◽  
Proton Pump ◽  
Bone Health ◽  
Current Evidence ◽  
Mineral Absorption ◽  
Number Of Patients ◽  
The Relationship ◽  
Fracture Risks

The number of patients with gastroesophageal problems taking proton pump inhibitors (PPIs) is increasing. Several studies suggested a possible association between PPIs and fracture risk, especially hip fractures, but the relationship remains contentious. This review aimed to investigate the longitudinal studies published in the last five years on the relationship between PPIs and fracture risk. The mechanism underlying this relationship was also explored. Overall, PPIs were positively associated with elevated fracture risk in multiple studies (n = 14), although some studies reported no significant relationship (n = 4). Increased gastrin production and hypochlorhydria are the two main mechanisms that affect bone remodeling, mineral absorption, and muscle strength, contributing to increased fracture risk among PPI users. As a conclusion, there is a potential relationship between PPIs and fracture risks. Therefore, patients on long-term PPI treatment should pay attention to bone health status and consider prophylaxis to decrease fracture risk.

scholarly journals Management of Globus Pharyngeus

2013 ◽  
Vol 2013 ◽  
pp. 1-5 ◽  
Author(s):  
S. Kortequee ◽  
P. D. Karkos ◽  
H. Atkinson ◽  
N. Sethi ◽  
D. C. Sylvester ◽  
...  
Keyword(s):  
Proton Pump Inhibitors ◽  
Significant Role ◽  
Proton Pump ◽  
Current Evidence ◽  
Extensive Investigation ◽  
Globus Pharyngeus ◽  
Laryngeal Injury ◽  
Benign Nature ◽  
Rigid Oesophagoscopy

Globus pharyngeus is a common ENT condition. This paper reviews the current evidence on globus and gives a rational guide to the management of patients with globus. The aetiology of globus is still unclear though most ENT surgeons believe that reflux whether acidic or not plays a significant role. Though proton pump inhibitors are used extensively in practice, there is little evidence to support their efficacy. Most patients with globus can be discharged after simple office investigations. The role of pepsin-induced laryngeal injury is an exciting concept that needs further study. Given the benign nature of globus pharyngeus, in most cases, reassurance rather than treatment or extensive investigation with rigid oesophagoscopy or contrast swallows is all that is needed. We need more research into the aetiology of globus.

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