Pantoprazole Does Not Reduce the Antiplatelet Effect of Clopidogrel: A Randomized Controlled Trial in Korea
2
조회
0
다운로드
0
인용
0
참고문헌
키워드
초록
Background/Aims: Concerns that proton pump inhibitors (PPIs) diminish the efficacy of clopidogrel could hamper the appropriate prescription of PPIs. We evaluated the influence of pantoprazole on the antiplatelet effect of clopidogrel compared with ranitidine, which is regarded as safe, after stratification of the population according to the presence of a cytochrome (CYP) 2C19 polymorphism in Korea. Methods: Forty patients who underwent dual antiplatelet therapy were randomized to receive pantoprazole (n=20) or ranitidine (n=20). Platelet aggregation was evaluated by impedance aggregometry at baseline (D0) and 8 days after acid-lowering treatments (D9). CYP2C19 was genotyped by polymerase chain reaction–restriction fragment length polymorphism. Results: After co-treatment, the percentage of clopidogrel low-response was 11.1% (2/18) in the pantoprazole group and 10.5% (2/19) in the ranitidine group (p=0.954). The impedance values with adenosine diphosphate stimulus after acid-lowering treatments did not significantly differ between the two groups. In a multiple regression analysis, only ST-elevation myocardial infarction was marginally associated with a reduced antiplatelet effect (odds ratio, 12.07; 95% confidence interval, 0.84 to 173.78). However, pantoprazole use did not affect the antiplatelet effect after correction for the CYP2C19 polymorphism. Conclusions: This study showed that pantoprazole does not increase platelet aggregation in patients receiving dual antiplatelet therapy (ClinicalTrials.gov number: NCT02733640).
Abstract
Background/Aims: Concerns that proton pump inhibitors (PPIs) diminish the efficacy of clopidogrel could hamper the appropriate prescription of PPIs. We evaluated the influence of pantoprazole on the antiplatelet effect of clopidogrel compared with ranitidine, which is regarded as safe, after stratification of the population according to the presence of a cytochrome (CYP) 2C19 polymorphism in Korea. Methods: Forty patients who underwent dual antiplatelet therapy were randomized to receive pantoprazole (n=20) or ranitidine (n=20). Platelet aggregation was evaluated by impedance aggregometry at baseline (D0) and 8 days after acid-lowering treatments (D9). CYP2C19 was genotyped by polymerase chain reaction–restriction fragment length polymorphism. Results: After co-treatment, the percentage of clopidogrel low-response was 11.1% (2/18) in the pantoprazole group and 10.5% (2/19) in the ranitidine group (p=0.954). The impedance values with adenosine diphosphate stimulus after acid-lowering treatments did not significantly differ between the two groups. In a multiple regression analysis, only ST-elevation myocardial infarction was marginally associated with a reduced antiplatelet effect (odds ratio, 12.07; 95% confidence interval, 0.84 to 173.78). However, pantoprazole use did not affect the antiplatelet effect after correction for the CYP2C19 polymorphism. Conclusions: This study showed that pantoprazole does not increase platelet aggregation in patients receiving dual antiplatelet therapy (ClinicalTrials.gov number: NCT02733640).
참고문헌 (39)
- Chang Kyu Choi, "Effect of Low-dose, Enteric Coated Aspirin on Gastrointestinal Bleeding in Patients with Coronary Artery Disease", Gut and Liver, 2(2), pp.99~104 (2008), 거트앤리버 발행위원회
- Bhatt DL, "ACCF", ACG, J Am Coll Cardiol, pp.2008, 52[DOI]
- Laine L, "Review article: gastrointestinal bleeding with low-dose aspirin: what’s the risk", Aliment Pharmacol Ther, 24, pp.897~908 (2006)
- Derry S, "Risk of gastrointestinal haemorrhage with long term use of aspirin: meta-analysis", BMJ, 321, pp.1183~1187 (2000)
- Yusuf S, "Effects of clopidogrel in addition to aspirin in patients with acute coronary syndromes without STsegment elevation", N Engl J Med, 345, pp.494~502 (2001)
- Ng FH, "Upper gastrointestinal bleeding in patients with aspirin and clopidogrel co-therapy", Digestion, 77, pp.173~177 (2008)
- Khean Lee Goh, "Pharmacological and Safety Profile of Dexlansoprazole: A New Proton Pump Inhibitor – Implications for Treatment of Gastroesophageal Reflux Disease in the Asia Pacific Region", Journal of Neurogastroenterology and Motility (JNM), 22(3), pp.355~366 (2016), 대한소화기 기능성질환∙운동학회[DOI]
- Furuta T, "Influence of CYP2C19 pharmacogenetic polymorphism on proton pump inhibitor-based therapies", Drug Metab Pharmacokinet, 20, pp.153~167 (2005)
- 신재무, "Pharmacokinetics and Pharmacodynamics of the Proton Pump Inhibitors", Journal of Neurogastroenterology and Motility (JNM), 19(1), pp.25~35 (2013), 대한소화기 기능성질환∙운동학회
- Gilard M, "Influence of omeprazole on the antiplatelet action of clopidogrel associated with aspirin: the randomized, double-blind OCLA (Omeprazole CLopidogrel Aspirin) study", J Am Coll Cardiol, 51, pp.256~260 (2008)
- Juurlink DN, "A population-based study of the drug interaction between proton pump inhibitors and clopidogrel", CMAJ, 180, pp.713~718 (2009)
- 이주엽, "Comparing the Areas of Interest in the Field of Functional Gastrointestinal Disorder and Neurogastroenterology and Motility Between the East and the West", Journal of Neurogastroenterology and Motility (JNM), 21(4), pp.503~510 (2015), 대한소화기 기능성질환∙운동학회[DOI]
- "Drug safety labeling changes" (2012)[URL]
- Neubauer H, "How to optimise clopidogrel therapy? Reducing the low-response incidence by aggregometry-guided therapy modification", Thromb Haemost, 99, pp.357~362 (2008)
- Ivandic BT, "Determination of clopidogrel resistance by whole blood platelet aggregometry and inhibitors of the P2Y12 receptor", Clin Chem, 52, pp.383~388 (2006)
- Herbert JM, "Clopidogrel, a novel antiplatelet and antithrombotic agent", Cardiovascul Drugs Rev, 11, pp.180~198 (1993)
- de Morais SM, "The major genetic defect responsible for the polymorphism of S-mephenytoin metabolism in humans", J Biol Chem, 269, pp.15419~15422 (1994)
- Choi KD, "Optimal dose of intravenous pantoprazole in patients with peptic ulcer bleeding requiring endoscopic hemostasis in Korea", J Gastroenterol Hepatol, 24, pp.1617~1624 (2009)
- "Drug safety labeling changes" (2011)[URL]
- Neubauer H, "Pantoprazole does not influence the antiplatelet effect of clopidogrel: a whole blood aggregometry study after coronary stenting", J Cardiovasc Pharmacol, 56, pp.91~97 (2010)
- Andersson T, "Drug interaction studies with esomeprazole, the (S)-isomer of omeprazole", Clin Pharmacokinet, 40, pp.523~537 (2001)
- Humphries TJ, "Review article: drug interactions with agents used to treat acid-related diseases", Aliment Pharmacol Ther, 13(Suppl 3), pp.18~26 (1999)
- Radhofer-Welte S, "Pharmacokinetics and metabolism of the proton pump inhibitor pantoprazole in man", Drugs Today (Barc), 35, pp.765~772 (1999)
- Cheer SM, "Pantoprazole: an update of its pharmacological properties and therapeutic use in the management of acid-related disorders", Drugs, 63, pp.101~133 (2003)
- De Morais SM, "Identification of a new genetic defect responsible for the polymorphism of (S)-mephenytoin metabolism in Japanese", Mol Pharmacol, 46, pp.594~598 (1994)
- Lim PW, "CYP2C19 genotype and the PPIs: focus on rabeprazole", J Gastroenterol Hepatol, 20(Suppl), pp.S22~S28 (2005)
- Kang JM, "Effect of the CYP2C19 polymorphism on the eradication rate of Helicobacter pylori infection by 7-day triple therapy with regular proton pump inhibitor dosage", J Gastroenterol Hepatol, 23(8 Pt 1), pp.1287~1291 (2008)
- Mega JL, "Cytochrome P450 genetic polymorphisms and the response to prasugrel: relationship to pharmacokinetic, pharmacodynamic, and clinical outcomes", Circulation, 119, pp.2553~2560 (2009)
- Rassen JA, "Cardiovascular outcomes and mortality in patients using clopidogrel with proton pump inhibitors after percutaneous coronary intervention or acute coronary syndrome", Circulation, 120, pp.2322~2329 (2009)
- O’Donoghue ML, "Pharmacodynamic effect and clinical efficacy of clopidogrel and prasugrel with or without a proton-pump inhibitor: an analysis of two randomised trials", Lancet, 374, pp.989~997 (2009)
- Bhatt DL, "Clopidogrel with or without omeprazole in coronary artery disease", N Engl J Med, 363, pp.1909~1917 (2010)
- Nguyen TA, "Resistance to clopidogrel: a review of the evidence", J Am Coll Cardiol, 45, pp.1157~1164 (2005)
- Furtado RH, "Drug Interaction between clopidogrel and ranitidine or omeprazole in stable coronary artery disease: a double-blind, double dummy, randomized study", Am J Cardiovasc Drugs, 16, pp.275~284 (2016)
- Furtado R, "Drug interaction between clopidogrel and ranitidine or omeprazole in patients with coronary heart disease: a double-blind, double-dummy, randomized comparative study", J Am Coll Cardiol, 63, pp.A1521~ (2014)
- Small DS, "Effect of ranitidine on the pharmacokinetics and pharmacodynamics of prasugrel and clopidogrel", Curr Med Res Opin, 24, pp.2251~2257 (2008)
- Bonello L, "Consensus and future directions on the definition of high on-treatment platelet reactivity to adenosine diphosphate", J Am Coll Cardiol, 56, pp.919~933 (2010)
- Jiang XL, "Clinical pharmacokinetics and pharmacodynamics of clopidogrel", Clin Pharmacokinet, 54, pp.147~166 (2015)
- 김성은, "Predictive Factors of Response to Proton Pump Inhibitors in Korean Patients With Gastroesophageal Reflux Disease", Journal of Neurogastroenterology and Motility (JNM), 21(1), pp.69~77 (2015), 대한소화기 기능성질환∙운동학회[DOI]
- Yang Won Min, "Recurrence and Its Impact on the Health-related Quality of Life in Patients with Gastroesophageal Reflux Disease: A Prospective Follow-up Analysis", Journal of Neurogastroenterology and Motility (JNM), 22(1), pp.86~93 (2016), 대한소화기 기능성질환∙운동학회[DOI]