Antiplatelet Function Of Clopidogrel Research Articles

Effects of atorvastatin and rosuvastatin on blood lipids, platelet aggregation rate and inflammatory factors in patients with cerebral infarction

Purpose: To investigate the effects of atorvastatin and rosuvastatin on blood lipids, platelet aggregation rate (PAR) and inflammatory factors in patients with cerebral infarction.Methods: Patients (n = 120) with cerebral infarction treated in Feng Hua People's Hospital, Jiang Feng Hua, China from January 2014 to October 2016 were randomly divided into control group (clopidogrel combined with atorvastatin, 60 cases) and observation group (clopidogrel combined with rosuvastatin, 60 cases). Blood lipids, PAR, inflammatory factors and carotid atherosclerotic plaque were recorded and compared.Results: Following treatment, total cholesterol (TC), triglycerides (TG) and low density lipoprotein cholesterol (LDL-C) in the observation group were significantly lower (p < 0.05) than in the control group, while high density lipoprotein cholesterol (HDL-C) was significantly higher (p < 0.05). C-reactive protein (CRP), tumor necrosis factor-α (IL-6) and interleukin-6 (IL-6) were significantly decreased in the two groups after treatment (p < 0.05). Plaque area, intima-media thickness (IMT) and number of plaques in the two groups were significantly lower after treatment than before treatment (p < 0.05). Plaque area, IMT and number of plaques in the observation group were significantly lower than those in the control group (p < 0.05).Conclusion: Atorvastatin and rosuvastatin have no significant effect on the antiplatelet function of clopidogrel, but rosuvastatin shows better control of blood lipids, carotid atherosclerosis and inflammatory factors.Keywords: Atorvastatin, Rosuvastatin, Cerebral infarction, Blood lipids, Platelet aggregation rate, Inflammatory factors

675 - Effect of Vonoprazan on the Anti-Platelet Function of Clopidogrel or Prasugrel in Relation to CYP2C19 Genotype

675 - Effect of Vonoprazan on the Anti-Platelet Function of Clopidogrel or Prasugrel in Relation to CYP2C19 Genotype

Influence of low-dose proton pump inhibitors administered concomitantly or separately on the anti-platelet function of clopidogrel.

Proton pump inhibitors (PPIs) at low doses can effectively prevent gastrointestinal bleeding due to aspirin and are widely used in Japan for gastroprotection in patients taking anti-platelet agents. We examined the influence of different PPIs at low doses administered concomitantly or separately on anti-platelet functions of clopidogrel. In 41 healthy Japanese volunteers with different CYP2C19 genotypes who took clopidogrel 75mg in the morning alone, or with omeprazole 10mg, esomeprazole 10mg, lansoprazole 15mg, or rabeprazole 10mg, either concomitantly in the morning or separately in the evening, we measured the inhibition of platelet aggregation (IPA, %) using VerifyNow P2Y12 assay at 4h after the last clopidogrel dose on Day 7 of each regimen. IPA by clopidogrel with rabeprazole administered at lunchtime, approximately 4h after clopidogrel, was also measured. Mean IPAs in those concomitantly receiving omeprazole, esomeprazole, lansoprazole or rabeprazole (47.2 ± 21.1%, 43.2 ± 20.2%, 46.4 ± 18.8%, and 47.3 ± 19.2%, respectively) were significantly decreased compared with those receiving clopidogrel alone (56.0%) (all ps < 0.001). This decrease was observed when PPIs were administered separately in the evening. However, IPA by clopidogrel with rabeprazole administered at lunchtime was 51.6%, which was markedly similar to that of clopidogrel alone (p = 0.114). All tested PPIs reduce the efficacy of clopidogrel when administered concomitantly. Our preliminary data suggest that administration of rabeprazole 4h following clopidogrel may minimize potential drug-drug interactions.

Sa1097 Influence of Low-Dose Proton Pump Inhibitors on Anti-Platelet Function of Clopidogrel

Sa1097 Influence of Low-Dose Proton Pump Inhibitors on Anti-Platelet Function of Clopidogrel

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

Dual antiplatelet therapy (DAPT) with aspirin and clopidogrel is essential after percutaneous coronary intervention (PCI). Clopidogrel is a prodrug and changed into active metabolite by cytochrome p450 enzymes (CYPs), especially CYP2C19. Proton pump inhibitors (PPIs) are used for the prevention of aspirin-induced gastrointestinal bleeding. PPIs are also metabolized by CYP2C19, although the degree of its contribution is dependent on the kind of PPI. Omeprazole, a PPI, has been reported to weaken the antiplatelet effects of clopidogrel. Famotidine, a histamine receptor type 2 (H2) blocker, could also be an alternative to PPIs. The aim of this study was to evaluate the effects of PPIs and an H2 blocker on the antiplatelet function of clopidogrel. Patients receiving DAPT due to prior PCI, who took either omeprazole or rabeprazole, were enrolled (n=25). The initial PPI was changed to the other PPI as a crossover study. In another study, patients undergoing DAPT without taking PPIs or H2 blockers were enrolled (n=30) and famotidine was added. Platelet aggregability when taking omeprazole was higher than when taking rabeprazole, evaluated by an optical aggregometer using collagen as a stimulus (p=0.0051) and by the VerifyNow P2Y12 assay (p=0.0060). Platelet aggregability when taking rabeprazole was comparable to that in control patients (n=15). Concomitant use of famotidine had no effect. Omeprazole significantly reduced the antiplatelet effect of clopidogrel and this effect on clopidogrel was stronger than that of rabeprazole. Concomitant use of famotidine had no effect on the antiplatelet effect of clopidogrel.

Proton Pumps Inhibitors and Clopidogrel Interaction: Effect of Rabeprazole on the Anti-Platelet Function of Clopidogrel in Relation to CYP2C19 Genotype Status. A Prospective, Randomized, 3-way Crossover PK/PD Study in Healthy Subjects

Proton Pumps Inhibitors and Clopidogrel Interaction: Effect of Rabeprazole on the Anti-Platelet Function of Clopidogrel in Relation to CYP2C19 Genotype Status. A Prospective, Randomized, 3-way Crossover PK/PD Study in Healthy Subjects

Influences of different proton pump inhibitors on the anti‐platelet function of clopidogrel in relation to CYP2C19 genotypes

Active metabolism of clopidogrel is mainly mediated by CYP2C19. There are genetic differences in the activity of CYP2C19. Therefore, active metabolism of clopidogrel is affected by CYP2C19 genotypes. The main metabolizing enzyme of proton pump inhibitors (PPIs) is CYP2C19. Therefore, the anti-platelet function of clopidogrel is attenuated by concomitant use of PPIs. There are differences in the metabolic disposition among different PPIs. Affinity to CYP2C19 differs among different PPIs. Whether a PPI attenuates the efficacy of clopidogrel depends on CYP2C19. Individuals who are decreased metabolizers, i.e. carriers the allele of CYP2C19*2 and/or *3, are more likely to convert from 'responder' to 'non-responder' to clopidogrel when placed on a concomitant PPI. We found that rabeprazole, whose affinity to CYP2C19 has been considered lower, attenuated the efficacy of clopidogrel. * We tested whether the separate dosing of a PPI and clopidogrel decreased the risk of attenuation of clopidogrel efficacy. We unfortunately found that separate dosing did not avoid the problematic interaction between clopidogrel and a PPI in subject's with CYP2C19*2 and/or CYP2C19*3. The efficacy of clopidogrel is influenced by CYP2C19 genotypes and substrates of CYP2C19, such as proton pump inhibitors (PPIs). We assessed the influence of three different PPIs on the anti-platelet function of clopidogrel in relation to CYP2C19 genotype status. Thirty-nine healthy volunteers with different CYP2C19 genotypes took clopidogrel 75 mg with or without omeprazole 20 mg, lansoprazole 30 mg or rabeprazole 20 mg in the morning for 7 days. The influence of the three PPIs on the anti-platelet function of clopidogrel was determined. A less than 30% inhibition of platelet aggregation (IPA) during clopidogrel dosing was defined as a 'low responder'. We also examined whether evening dosing of omeprazole could prevent the interaction with clopidogrel dosed in the morning. In rapid metabolizers (RMs, *1/*1, n=15) of CYP2C19, omeprazole and rabeprazole significantly attenuated the anti-platelet function of clopidogrel. In decreased metabolizers (DMs, carriers of *2 and/or *3, n=24), there was a large variation in IPA and there was a trend but no significant decrease in IPA when placed on a concomitant PPI. Some DMs became 'low-responders' when placed on a concomitant PPI. Evening omeprazole dose in RMs did not seem to cause a significant decrease in IPA in contrast to morning dosing, but did so in DMs. The three PPIs affected the efficacy of clopidogrel to different degrees. Both omeprazole and rabeprazole significantly decreased IPA in RMs but not DMs, although there was a trend towards lower IPA in DMs. Morning and evening dosing of omeprazole were both associated with lower IPA in DMs.

13C]Pantoprazole breath test as a predictor of the anti-platelet function of clopidogrel

Clopidogrel, a platelet inhibitor, is metabolized by cytochrome P450 2C19 (CYP2C19) to its active metabolite and, consequently, its anti-platelet efficacy is influenced by CYP2C19 activity. The aim of this study was to determine whether the [(13)C]pantoprazole breath test, a recently developed tool used to measure CYP2C19 activity, can predict the anti-platelet efficacy of clopidogrel. Seventy healthy volunteers with different CYP2C19 genotypes received 100 mg of [(13)C]pantoprazole. Breath samples were collected at 10-min intervals for 60 min, and changes in the carbon isotope ratios ((13)CO(2)/(12)CO(2)) from the baseline level were measured and expressed as a delta-over-baseline (DOB) ratio (per thousand). After a washout period of > 2 weeks, the subjects underwent a platelet aggregation test before and after dosing with 75 mg of clopidogrel for 7 days. The percentage inhibition of platelet aggregation (IPA, %) was then calculated. There was a statistically significant correlation between the area under the curve (AUC)(20-60 min) of the DOB and IPA at 4 h attained by clopidogrel. The mean AUC(20-60 min) of the DOB of the "low-responder" (IPA < 20%) group was significantly lower than that of the responder group (IPA > or = 20%). The results of our preliminary study suggest that the [(13)C]pantoprazole breath test can predict the anti-platelet efficacy of clopidogrel.