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Volume 42 (2011)
- Issue 6 Pages 355-
- Issue 5 Pages 297-
- Issue 4 Pages 205-
- Issue 3 Pages 111-
- Issue 2 Pages 33-
- Issue 1 Pages 1-
Volume 42, Issue 6
Displaying 1-8 of 8 articles from this issue
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Feature Articles: Current Topics on Proton Pump Inhibitors and Antiplatelet Drugs, Clopidogrel and Prasugrel
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Takahisa FURUTA, Hirotoshi ECHIZEN2011 Volume 42 Issue 6 Pages 355
Published: 2011
Released on J-STAGE: December 29, 2011
JOURNAL RESTRICTED ACCESSDownload PDF (92K) -
Hirotoshi ECHIZEN2011 Volume 42 Issue 6 Pages 357-360
Published: 2011
Released on J-STAGE: December 29, 2011
JOURNAL RESTRICTED ACCESSProton pump inhibitors (PPI) are frequently prescribed with thienopyridine antiplatelet drugs (clopidogrel and prasugrel) for the prevention of upper gastrointestinal mucosal damages. However, recent studies have casted doubt on this combination, because several retrospective cohort studies have suggested a possible detrimental drug interaction between these drugs, particularly in patients undergoing percutaneous coronary intervention and stenting. Lines of robust in vitro and in vivo evidence have shown that PPIs are potent inhibitors of CYP2C19 activity in human liver microsomes and that PPIs reduce the production of the active metabolite of clopidogrel, thus attenuating its antiplatelet activity in patients. In addition, it is known that genetic polymorphism of CYP2C19 is associated with loss of CYP2C19 enzyme activity and that drug interactions of PPI with CYP2C19 substrate drugs occur only in subjects with the extensive metabolizer phenotype of CYP2C19. Because Asians possess higher allelic frequencies of loss-of-function alleles of this CYP isoform than Caucasians, they may be less susceptible to the drug interactions between PPI and thienopyridines. In contrast to clopidogrel, metabolic activation of prasugrel is not affected by PPIs, because multiple CYP isoforms are involved. At present, no prospective randomized studies have been reported, which provide reliable risk-benefit data for the coadministration of PPI with thienopyridine antiplatelet drugs both in Caucasians and Asians.View full abstractDownload PDF (236K) -
Mitsushige SUGIMOTO, Takahiro UOTANI, Masafumi NISHINO, Mihoko YAMADE, ...2011 Volume 42 Issue 6 Pages 361-367
Published: 2011
Released on J-STAGE: December 29, 2011
JOURNAL RESTRICTED ACCESSClopidogrel, an anti-platelet drug, is converted to its active metabolite by cytochrome P450 (CYP) enzymes such as CYP2C19. Clopidogrel users with decreased CYP2C19 function, especially CYP2C19 poor metabolizers, have been reported to exhibit less inhibition of platelet aggregation and increased cardiovascular (CV) events. As metabolism of proton pump inhibitors (PPIs) involves CYP2C19, a hypothesis that competition by PPIs may interfere with clopidogrel-induced anti-platelet action is raised. Although a retrospective cohort study suggested that clopidogrel users prescribed PPIs had increased risks of CV events, a prospective randomized trial of omeprazole vs. placebo showed no difference in CV events. Therefore, the current evidence does not justify the conclusion that PPIs decrease the clinical efficacy of clopidogrel, and further study is required to clarify this discrepancy. Combination therapy of clopidogrel and aspirin causes the development of gastric mucosal injury and gastrointestinal bleeding, which is sometimes lethal. Therefore, current consensus recommendations state that patients prescribed clopidogrel plus aspirin should receive a PPI to reduce gastrointestinal mucosal injury and bleeding. Physicians should consider the possibility of increased CV risk and gastrointestinal bleeding by concomitant clopidogrel plus aspirin treatment, and select the appropriate treatment for patients with cardiovascular diseases upon considering the benefit and risk.View full abstractDownload PDF (397K) -
Hiroshi YASUDA2011 Volume 42 Issue 6 Pages 369-373
Published: 2011
Released on J-STAGE: December 29, 2011
JOURNAL RESTRICTED ACCESSClopidogrel is an antiplatelet drug that is used in patients who have had previous cerebrovascular events, acute coronary syndromes, or percutaneous coronary interventions (PCI). Clopidogrel therapy is associated with bleeding complications, and gastrointestinal bleeding has been reported as one of the most common life-threatening complications. This review focuses on the possible interaction between clopidogrel and CYP2C19, a known site of PPI metabolism. This interaction attenuates the antiplatelet effect of clopidogrel and seems to worsen cardiovascular outcome. Alternative concomitant therapy is also discussed.View full abstractDownload PDF (276K) -
Seiji HOKIMOTO, Hisao OGAWA2011 Volume 42 Issue 6 Pages 375-381
Published: 2011
Released on J-STAGE: December 29, 2011
JOURNAL RESTRICTED ACCESSClopidogrel is a prodrug that has to be converted to an active metabolite. CYP2C19 genotype is a key factor impacting the response to clopidogrel and the drug interaction between proton pump inhibitors (PPIs) and clopidogrel. The prevalence of CYP2C19 loss-of-function alleles is much higher in East Asians including Japanese, than in people in Western countries. The American College of Cardiology Foundation (ACCF), American College of Gastroenterology (ACG) and American Heart Association (AHA) recommended in a 2010 conference that it is acceptable to use PPI with thienopyridines such as clopidogrel in patients at high risk of upper gastrointestinal bleeding. Several studies have indicated that concomitant use of clopidogrel and PPI is associated with reduced antiplatelet efficacy of clopidogrel, and increased adverse clinical outcomes after stent implantation in patients with acute coronary syndrome. However, several reports show that concomitant use of PPI and clopidogrel after stent implantation is not associated with an increased risk of cardiovascular events. We investigated whether CYP2C19 polymorphism or concomitant use of PPI and clopidogrel is associated with on-treatment platelet reactivity and clinical outcomes following stent implantation in patients with coronary artery disease. Our results indicated that the presence of CYP2C19 loss-of-function allele, but not the use of a PPI, was associated with an increased risk of cardiovascular outcomes. In conclusion, the use of a PPI should not be hesitated in patients with a high risk of gastrointestinal bleeding or ulcer.View full abstractDownload PDF (820K) -
Keiichiro YAMANE, Hisanori HORIUCHI2011 Volume 42 Issue 6 Pages 383-388
Published: 2011
Released on J-STAGE: December 29, 2011
JOURNAL RESTRICTED ACCESSDual antiplatelet therapy with aspirin and clopidogrel is essential after percutaneous coronary intervention. Clopidogrel is a prodrug and requires metabolism by cytochrome p450 enzymes (CYPs), especially CYP2C19.
Proton pump inhibitors (PPIs) are used for the prevention of aspirin-induced gastrointestinal bleeding. PPIs are metabolized by CYP2C19. Concomitant use of PPI in dual antiplatelet therapy diminishes the antiplatelet effect of clopidogrel, although it is controversial whether its clinical efficacy is reduced. The US FDA and European Medicines Agency recommend that PPIs and clopidogrel should not be coadministered routinely, and the 2010 expert consensus of ACCF/ AGC/ AHA supports this recommendation.
On the other hand, histamine receptor type2 (H2) blockers also reduce gastric acid secretion and are used for the treatment of gastroduodenal ulcers. Famotidine, an H2 blocker, has been shown recently to reduce gastric mucosal injury caused by aspirin therapy, although the protective effects of H2 blockers are weaker than that of PPI.
Therefore, H2 blockers except cimetidine, which is inactivated by CYP2C19, could be an alternative for PPI in patients treated with clopidogrel, who are at risk of low gastrointestinal tract bleeding.View full abstractDownload PDF (364K)
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Eri IKEDA2011 Volume 42 Issue 6 Pages 389-399
Published: 2011
Released on J-STAGE: December 29, 2011
JOURNAL RESTRICTED ACCESSTo elucidate the factors affecting the intention of clinical research coordinators (CRCs) to stay on their job, we conducted a questionnaire to examine the career consciousness and professional identity of CRCs. A questionnaire was mailed to CRCs working in hospitals or site management organizations (SMO) in Japan. Analysis of the data yielded the following results:
1. Analysis of career consciousness of CRCs revealed that they placed the highest value on “career commitment”. Conversely, reflecting the uncertainty about the future prospect for CRC, they placed the lowest value on “career goal commitment”, and few CRCs sought consultations with their supervisors. Regarding “career satisfaction”, they placed higher values on work experience, and lower values on income and promotion.
2. Analysis of professional identity of CRCs showed the highest value on “aspiration to contribute to the society”, and the lowest value on “confidence in selecting CRC as a career and in self-improvement”. Because the CRCs considered the relationship with trial participants to be valuable, the acquisition of expertise as a CRC could facilitate the establishment of professional identity.
3. The proportion of CRCs who intended to continue pursuing this career was high (80%), and career consciousness and professional identity were significantly higher in those who intended to stay on the job as CRC than those who did not, regardless of their affiliations.
4. CRCs who had intention to continue pursuing CRC as their career were characterized by high scores of “career commitment”, while those who had no such intention were characterized by low scores of “professional identity”.
In conclusion, actions should be taken to improve carrier consciousness and professional identity of CRCs in order to increase their motivation to continue pursuing CRC as a life career.View full abstractDownload PDF (394K) -
Keiko FUNAHASHI, Tetsuya TAKAMATSU, Tsukasa MATSUBARA2011 Volume 42 Issue 6 Pages 401-407
Published: 2011
Released on J-STAGE: December 29, 2011
JOURNAL RESTRICTED ACCESSWe have conducted many clinical trials in patients with rheumatoid arthritis (RA). However, in the past few years, we have met challenges in the selection of patients as subjects for clinical trials. To have a better understanding of the present situation, we analyzed the background in selecting and excluding patients in 18 clinical trials. Fifteen trials required inflammatory findings of CRP or sedimentation rate, and 14 of these 15 trials required CRP of 1.0 or above. Combined use of MTX began to be prescribed in trials after 2005, and became increasingly common until MTX was used in all trials from 2008. Improvement in clinical conditions, imaging findings and QOL became the treatment goal. Compared to 10 years ago, the average inflammatory level of RA in patients showed a statistically significant decrease from 2.4 mg/dL to 0.7 mg/dL in CRP, and from 43.7 mm/h to 33.6 mm/h in ESR. With this trend, although 5 trials conducted in 2009 reached 100% achievement rate, the consent rates were 220% or higher in 3 of the 5 trials. These data suggest that there is difficulty in including patients for clinical trials, i.e., many patients agree to participate, but are excluded due to the current selection criteria. This issue has drawn global attention, and selection criteria have been reviewed overseas. International clinical trial protocols are increasingly being used in Japan without any modification despite differences in clinical practices. It's important to modify selection criteria properly in response to the changing guidelines for RA treatment. Such changes will improve the patient inclusion rate and facilitate development of future treatment guidelines.View full abstractDownload PDF (340K)
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