Impact of Proton-pump Inhibitors on the Pharmacodynamic Effect and Clinical Outcomes in Patients Receiving Dual Antiplatelet Therapy after Percutaneous Coronary Intervention

Zhu, Peng; Gao, Zhan; Tang, Xiaofang; Zhang, Yin; Gao, Lijian; Chen, Jue; Qiao, Shubin; Yang, Yuejin; Gao, Runlin; Xu, Bo; Yuan, Jinqing

doi:10.4103/0366-6999.220304

Cited by 13 publications

(19 citation statements)

References 23 publications

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“…The results of the study and a systematic review clearly showed that clopidogrel-induced inhibition of platelet aggregation is weakened by the co-administration of PPIs, although some reports showed that rabeprazole, which is not mainly metabolized by CYP2C19, did not statistically significantly attenuate the anti-thrombotic effect of clopidogrel. [49][50][51][52] This consistent pharmacodynamic study result, however, was not confirmed in clinical studies. Firstly performed epidemiological study supported this concept and suggested that PPIs interfered with clopidogrel activation and elevated cardiovascular risk.…”

Section: Drug Interaction During Activation And/or Degradation Phase mentioning

confidence: 72%

Advantages and Disadvantages of Long-term Proton Pump Inhibitor Use

Kinoshita

Ishimura

Ishihara

2018

J Neurogastroenterol Motil

196

172

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Proton pump inhibitors (PPIs) potently inhibit gastric acid secretion and are widely used for treatment of acid-related diseases including gastroesophageal reflux disease and secondary prevention of aspirin/NSAID-induced ulcers. Although clinically important adverse effects of PPIs can occur, just as with other drugs, those are not frequently observed during or after administration. Thus, PPIs are regarded as relatively safe and considered to be clinically beneficial. Recently, PPIs have become frequently administered to patients with functional gastrointestinal diseases or primary prevention of drug-related gastroduodenal damage, even though their beneficial effects for those conditions have not been fully confirmed. PPIs tend to be given for conditions in which the necessity of the drug has not been clarified, thus otherwise rare adverse effects are presented as clinically relevant. Although several PPI-related adverse effects have been reported, their clinical relevance is not yet clear, since the evidence reported in those studies is not at a high enough level, as the majority are based on retrospective observational studies and the reported hazard ratios are low. It is important to administer PPIs only for patients who will gain a substantial clinical benefit and to continue to investigate their adverse effects with high quality prospective studies.

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Section: Drug Interaction During Activation And/or Degradation Phase mentioning

confidence: 72%

Advantages and Disadvantages of Long-term Proton Pump Inhibitor Use

Kinoshita

Ishimura

Ishihara

2018

J Neurogastroenterol Motil

196

172

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“…Other important predictors of MACE in our local population include diabetes, Malay ethnic group (compared to Chinese) and PPI use. Several meta‐analyses, registry and observational studies suggest no impact of PPI on clopidogrel MACE rates; however, a study on genetic cofactors, investigating the effect of omeprazole use on platelet reactivity, revealed that the only predictor of poor response was the presence of CYP2C19*2 mutation . It could be surmised that drug–gene interactions could be more significant when polymorphisms were more prevalent.…”

Section: Discussionmentioning

confidence: 99%

“…was the presence of CYP2C19*2 mutation. [18][19][20][21][22] It could be surmised that drug-gene interactions could be more significant when polymorphisms were more prevalent. Based on the incidence rates of MACE in the PM vs NM population in our study, for a 95% confidence interval and 80% analysis, a mere 121 subjects are required and thus would likely be adequately powered.…”

Section: Ta B L Ementioning

confidence: 99%

CYP2C19 phenotype in South‐East Asian Acute Coronary Syndrome patients and impact on major adverse cardiovascular events

Tan¹,

Winther

et al. 2019

J Clin Pharm Ther

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What is known and objective: Several Caucasian cohort studies have associated at least one loss-of-function CYP2C19 on Clopidogrel (LoF-Clopidogrel) with major adverse cardiovascular events (MACE), and only a couple have used Clinical Pharmacogenetics Implementation Consortium (CPIC ®) phenotype grouping to study the associations. We primarily aimed to study the impact of use of platelet reactivity testing to escalate antiplatelet therapy and secondarily to study the association of CPIC phenotype with MACE outcomes in SouthEast Asian Acute Coronary Syndrome (ACS) subjects. Method: A retrospective genotype study was performed on 238 percutaneous coronary intervention subjects, originally planned for escalation of antiplatelets using platelet reactivity testing. Results and discussion: There was no difference in MACE between the switched and unswitched groups; however, 'all bleeds' and 'clinically significant bleeds' (CSB) were statistically higher in the patients who were switched to prasugrel. The subgroup of patients who remained on clopidogrel (n = 199) were analysed using phenotype categories and MACE. Eleven percent (11.4%) of CYP2C19 poor metabolizers (PM) suffered MACE, compared with 1.3% of extensive metabolizers (EM). LoF-Clopidogrel patients are significantly more likely to experience MACE compared with non-LoF subjects (8.0% vs 5.4%, P: .041). What is new and conclusion: In our multivariate analysis, LoF-Clopidogrel, malay ethnicity, diabetics and use of proton pump inhibitors were independent predictors of MACE. There were numerically more bleeds in LoF subjects who were on prasugrel compared with Clopidogrel (23.5% vs 11%, P = .082). Our data corroborate with current findings on platelet reactivity testing, suggesting that the assay would not be sensitive enough to pick up sufficient 'at-risk' subjects as compared to the use of CYP2C19 genotyping.

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“…Lower levels of the active metabolite of clopidogrel and higher residual platelet reactivity to ADP were described in clopidogrel-treated patients who concomitantly received PPIs. [59][60][61] This may be due to a drug interaction at the level of hepatic biotransformation of clopidogrel to its active metabolite by the cytochrome P450 enzyme system and was seen particularly in patients receiving omeprazole. 59,61 However, in the prospective and randomized Clopidogrel and the Optimization of Gastrointestinal Events Trial (COGENT), the authors observed no difference in the occurrence of adverse cardiovascular outcomes between clopidogrel-treated patients on omeprazole therapy and those receiving placebo.…”

Section: Discussionmentioning

confidence: 99%

Low Levels of High-Density Lipoprotein Cholesterol Are Linked to Impaired Clopidogrel-Mediated Platelet Inhibition

et al. 2018

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Low high-density lipoprotein cholesterol (HDL-C) levels are an independent predictor of ischemic events in patients with atherosclerotic cardiovascular disease. This may in part be due to decreased clopidogrel-mediated platelet inhibition in patients with low HDL-C. We investigated the association of HDL-C with on-treatment platelet reactivity to adenosine diphosphate (ADP) in 314 patients on dual antiplatelet therapy with clopidogrel and aspirin undergoing angioplasty and stenting. Platelet P-selectin expression was assessed by flow cytometry, and platelet aggregation was determined by the VerifyNow P2Y assay and the Impact-R. High-density lipoprotein cholesterol levels were inversely associated with P-selectin expression and the VerifyNow P2Y assay (both P ≤ .01). Moreover, we found a positive correlation of HDL-C with surface coverage by the Impact-R ( P = .003). Patients with low HDL-C (≤35 mg/dL) exhibited a significantly higher P-selectin expression in response to ADP and higher platelet aggregation by the VerifyNow P2Y assay and the Impact-R than patients with normal HDL-C (>35 mg/dL; all P < .05). High on-treatment residual platelet reactivity by the VerifyNow P2Y assay occurred significantly more frequently in patients with low HDL-C levels than in those with normal HDL-C (47.4% vs 30.1%, P = .01). In conclusion, low HDL-C is linked to impaired clopidogrel-mediated platelet inhibition after angioplasty and stenting.

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Impact of Proton-pump Inhibitors on the Pharmacodynamic Effect and Clinical Outcomes in Patients Receiving Dual Antiplatelet Therapy after Percutaneous Coronary Intervention

Cited by 13 publications

References 23 publications

Advantages and Disadvantages of Long-term Proton Pump Inhibitor Use

Advantages and Disadvantages of Long-term Proton Pump Inhibitor Use

CYP2C19 phenotype in South‐East Asian Acute Coronary Syndrome patients and impact on major adverse cardiovascular events

Low Levels of High-Density Lipoprotein Cholesterol Are Linked to Impaired Clopidogrel-Mediated Platelet Inhibition

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