Serial changes in platelet activation biomarkers and the effects of anti-platelet therapy in percutaneous coronary intervention

• Project/Area Number: 21590903
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Circulatory organs internal medicine
• Research Institution: Kumamoto University
• Principal Investigator: KAIKITA Koichi 熊本大学, 医学部附属病院, 講師 (30346978)
• Research Collaborator: ONO Takamichi 熊本大学, 医学教育部, 学生
• Project Period (FY): 2009 – 2011
• Project Status: Completed (Fiscal Year 2011)
• Budget Amount: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000); Fiscal Year 2011: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2010: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2009: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
• Keywords: 循環器・高血圧 / 遺伝子 / 経皮的冠動脈インターベンション / クロピドグレル / CYP2C19遺伝子多型 / VerifyNow system / 冠動脈疾患 / Verify Now system / CYP2C19遺伝子

Research Abstract

We investigated the effects of CYP2C19 gene variants on platelet function tests and biomarkers of coagulation activation and inflammation in patients undergoing elective percutaneous coronary intervention(PCI). Only on-clopidogrel residual platelet aggregation was associated with the CYP2C19-reduced function allele in patients treated with clopidgrel. These platelet function tests may be useful for identifying carriers of CYP2C19 reduced-function gene variants and monitoring the efficacy of dual antiplatelet therapy in patients undergoing elective PCI.

Research Products

• [Journal Article] Determination of Cut-off Levels for On-clopidogrel Platelet Aggregation Based on Functional CYP2C19 Gene Variants in Patients Undergoing Elective Percutaneous Coronary Intervention (2011)
  • Author(s): Ono T, Kaikita K, Hokimoto S, Iwashita S, Yamamoto K, Miyazaki Y, Horio E, Sato K, Tsujita K, Abe T, Deguchi M, Tayama S, Sumida H, Sugiyama S, Yamabe H, Nakamura S, Nakagawa K, Ogawa H
  • Journal Title: Thromb Res Volume: 128
  • Peer Reviewed
• [Journal Article] Current status and prospects of antiplatelet therapy in percutaneous coronary intervention in Japan : Focus on adenosine diphosphate receptor inhibitors (2011)
  • Author(s): Ogawa H, Hokimoto S, Kaikita K, Yamamoto K, Chitose T, Ono T, Tsujita K
  • Journal Title: J Cardiol Volume: 58 Pages: 6-17
  • NAID: 10031159568
  • Peer Reviewed
• [Journal Article] Determination of Cut-off Levels for On-clopidogrel Platelet Aggregation Based on Functional CYP2C19 Gene Variants in Patients Undergoing Elective Percutaneous Coronary Intervention (2011)
  • Author(s): Ono T, Kaikita K, et al
  • Journal Title: Thromb Res Volume: 128
  • Peer Reviewed
• [Journal Article] Impact of CYP2C19 polymorphism on residual platelet reactivity in patients with coronary heart disease during antiplatelet therapy (2010)
  • Author(s): Yamamoto K, Hokimoto S, Chitose T, Morita K, Ono T, Kaikita K, Tsujita K, Abe T, Deguchi M, Miyagawa H, Saruwatari J, Sumida H, Sugiyama S, Nakagawa K, Ogawa H
  • Journal Title: J Cardiol Volume: 57 Pages: 194-201
  • NAID: 10031159562
  • Peer Reviewed
• [Journal Article] Prognostic value of plasma von Willebrand factor-cleaving protease(ADAMTS 13)antigen levels in patients with coronary artery disease (2010)
  • Author(s): Mitsutoshi Miura, Koichi Kaikita
  • Journal Title: Thromb Haemost.
• [Presentation] Influence of CYP2C19 Gene Variants on Serial Changes of Platelet Function Tests and Biomarkers in Patients Undergoing Elective Percutaneous Coronary Intervention (2012)
  • Author(s): Ono T, Kaikita K
  • Organizer: 第76回日本循環器学会総会
  • Place of Presentation: マリンメッセ福岡、福岡
  • Year and Date: 2012-03-18
• [Presentation] Impact of Cytochrome P450 3A5 Polymorphism on Platelet Aggregation on Maintenance Treatment with Clopidogrel in Patients Undergoing Elective Coronary Stenting (2012)
  • Author(s): Chitose T, Hokimoto S, Mizobe M, Yamamoto K, Ono T, Tsujita K, Tayama S, Kaikita K, Nakagawa K, Ogawa H
  • Organizer: American College of Cardiology 2012
  • Place of Presentation: シカゴ、米国
• [Presentation] Functional CYP2C 19 Gene Variants are Associated With Both On-clopidogrel Platelet Adhesiveness and Aggregation in Japanese Patients With Coronary Artery Disease (2011)
  • Author(s): Takamichi Ono, Koichi Kaikita
  • Organizer: 第75回日本循環器学会総会
  • Place of Presentation: パシフィコ横浜、横浜
  • Year and Date: 2011-03-19
• [Presentation] Impact of CYP2C19 Polymorphism and Diabetes Mellitus on Platelet Reactivity and Clinical Outcomes in Patients Following Coronary Stent Placement (2011)
  • Author(s): Hokimoto S, Mizobe M, Chitose T, Kaikita K, Nakagawa K, Ogawa H
  • Organizer: American Heart Association Scientific Sessions 2011
  • Place of Presentation: オーランド、米国
• [Presentation] Impact of Proton Pump Inhibitor(PPI) and CYP2C19 Polymorphism on Clinical Outcomes in Acute Coronary Syndrome(ACS) Patients (2011)
  • Author(s): Hokimoto S, Yamamoto K, Chitose T, OnoT, Kaikita K, Tsujita K, Nakagawa K, Sumida H, Sugiyama S, Ogawa H
  • Organizer: 第75回日本循環器学会総会・学術集会
  • Place of Presentation: パシフィコ横浜、横浜
• [Presentation] Impact of CYP2C19 Polymorphism on Residual Platelet Reactivity in Patients with Coronary Heart Disease during Antiplatelet Therapy (2011)
  • Author(s): Yamamoto K, Hokimoto S, Chitose T, Ono T, Izumiya Y, Tsujita K, Kaikita K, Sumida H, Sugiyama S, Nakagawa K, Ogawa H
  • Organizer: 第75回日本循環器学会総会・学術集会
  • Place of Presentation: パシフィコ横浜、横浜
• [Presentation] Besides CYP2C19 Polymorphism, Genetic Variation of CYP3A5 is Associated with Higher Ontreatment Platelet Reactivity in Patients Undergoing Coronary Stenting (2011)
  • Author(s): Yamamoto K, Hokimoto S, Chitose T, Ono T, Izumiya Y, Tsujita K, Tayama S, Kaikita K, Sumida H, Sugiyama S, Nakagawa K, OgawaH
  • Organizer: 第75回日本循環器学会総会・学術集会
  • Place of Presentation: パシフィコ横浜、横浜
• [Presentation] Determination of Optimal Cut-Off Value in On-Clopidogrel Platelet Aggregation by VerifyNow P2Y12 System Based on Functional CYP2C19 Gene Variants (2011)
  • Author(s): Ono T, Kaikita K, Sato K, Horio E, Chitose T, Yamamoto K, Tsujita K, Tayama S, Hokimoto S, Sumida H, Sugiyama S, Yamabe H, Morita K, Nakagawa K, Ogawa H
  • Organizer: 第75回日本循環器学会総会・学術集会
  • Place of Presentation: パシフィコ横浜、横浜
• [Presentation] Impact of CYP2C19 Polymorphism and Diabetes Mellitus on Platelet Reactivity and Clinical Outcomes in Patients Following Coronary Stent Placement (2011)
  • Author(s): Hokimoto S, Mizobe M, Chitose T, Kaikita K, Nakagawa K, Ogawa H
  • Organizer: 第20回日本心血管インターベンション治療学会/CVIT2011
  • Place of Presentation: 大阪国際会議場、大阪
• [Presentation] Optimal Cut-off Levels for On-clopidogrel platelet Aggregation Based on Functional CYP2C19 Gene Variants in Patients Undergoing Elective Percutaneous Coronary Intervention (2011)
  • Author(s): Kaikita K, Ono T, Hokimoto S, Yamamoto K, Tsujita K, Tayama S, Sumida H, Sugiyama S, Nakazawa K, Nakamura S, Ogawa H
  • Organizer: 第20回日本心血管インターベンション治療学会/CVIT2011
  • Place of Presentation: 大阪国際会議場、大阪
• [Presentation] Determination of Optimal Cut-Off Value in On-Clopidogrel Platelet Aggregation by VerifyNow P2Y12 System Based on Functional CYP2C19 Gene Variants (2011)
  • Author(s): Ono T, Kaikita K, Hokimoto S, Yamamoto K, Miyazaki Y, Sakamoto K, Tsujita K, Iwashita S, Sumida H, Sugiyama S, Yamabe H, Ogawa H
  • Organizer: American College of Cardiology 2011
  • Place of Presentation: ニューオーリンズ、米国
• [Presentation] Impact of CYP2C19 Polymorphism on Development of Acute Coronary Syndrome(ACS) in Patients with Decreased Plasma Low-Density Lipoprotein Cholesterol(LDL-C) (2011)
  • Author(s): Chitose T, Hokimoto S, Yamamoto K, Ono T, Tsujita K, Kaikita K, Sumida H, Sugiyama S, Ogawa H
  • Organizer: American College of Cardiology 2011
  • Place of Presentation: ニューオーリンズ、米国
• [Presentation] Functional CYP2C19 Gene Variants are Associated With Both On-clopidogrel Platelet Adhesiveness and Aggregation in Japanese Patients With Coronary Artery Disease (2010)
  • Author(s): Koichi Kaikita
  • Organizer: AHA Scientific Sessions 2010
  • Place of Presentation: McCormick Place Convention Center, Chicago, U.S.A.
  • Year and Date: 2010-11-17
• [Presentation] Prognostic value of plasma von Willebrand factor-cleaving protease(ADAMTS 13)antigen levels in patients with coronary artery disease (2010)
  • Author(s): Mitsutoshi Miura, Koichi Kaikita
  • Organizer: 日本循環器学会学術集会
  • Place of Presentation: 京都国際会館(京都府)
  • Year and Date: 2010-03-06
• [Presentation] Functional CYP2C19 Gene Variants are Associated With Both On-clopidogrel Platelet Adhesiveness and Aggregation in Japanese Patients With Coronary Artery Disease (2010)
  • Author(s): Kaikita K, Ono T, Hokimoto S, Tsujita K, Miyazaki Y, Sato K, Horio E, Sumida H, Sugiyama S, Ogawa H
  • Organizer: American Heart Association Scientific Sessions 2010
  • Place of Presentation: Chicago, Illinois
• [Presentation] Do Use of Proton Pump Inhibitor(PPI) and CYP2C19 Polymorphism Have the Same Degree of Impact on Cardiovascular Outcomes in Patients with Acute Coronary Syndrome(ACS) (2010)
  • Author(s): Hokimoto S, Yamamoto K, Chitose T, Ono T, Kaikita K, Tsuijita K, Nakagawa K, Ogawa H
  • Organizer: American Heart Association Scientific Sessions 2010
  • Place of Presentation: Chicago, Illinois