Aspirin Response in High Risk Patients With Coronary Artery Disease
Is a Reduced Biochemical Response to Aspirin Associated With Increased Cardiovascular Morbidity and Mortality in High Risk Patients With Coronary Artery Disease?
Previous studies indicate that patients with cardiovascular disease have a variable response to aspirin. Despite treatment with aspirin a large number of patients suffer a myocardial infarction. This has given rise to the phenomenon "aspirin low-responsiveness". Laboratory aspirin low-responsiveness can be defined as the failure of aspirin to inhibit platelet production of thromboxane A2 or inhibit thromboxane-dependent platelet aggregation. Whether a low platelet response to aspirin results in an increased risk of future thrombotic events is of great clinical significance, but is still unknown.
The investigators hypothesize that patients with a reduced response to aspirin, determined by platelet aggregation using the apparatus Verify Now Aspirin and Multiplate, have a higher risk of thrombosis.
The purpose of this study is to investigate whether a higher incidence of cardiovascular events is found in patients with coronary artery disease (CAD) having a reduced biochemical response to aspirin compared with CAD patients having a normal biochemical response to aspirin. In addition to CAD, all patients have at least one of the following risc factors: previous myocardial infarction, type 2 diabetes mellitus and/or renal insufficiency.
調査の概要
研究の種類
入学 (実際)
連絡先と場所
研究場所
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Aarhus N、デンマーク、8200
- Department of Clinical Biochemistry, Aarhus University Hospital, Skejby
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参加基準
適格基準
就学可能な年齢
健康ボランティアの受け入れ
受講資格のある性別
サンプリング方法
調査対象母集団
906 patients with CAD. In addition to CAD, all patients have at least one of the following risc factors: previous myocardial infarction, type 2 diabetes mellitus and/or renal insufficiency.
Eligible patients are identified in the Western Denmark Heart Registry.
説明
Inclusion Criteria:
- Coronary artery disease verified by coronary angiogram
- Treatment with aspirin 75 mg/d for at least the previous 7 days
- Previous myocardial infarction more than one year ago (groups with previous myocardial infarction)
- Type 2 diabetes mellitus treated with oral antidiabetics and/or insulin (groups with type 2 diabetes mellitus)
- Renal insufficiency; glomerular filtration rate <60 ml/min at the time of blood sampling (groups with renal insufficiency)
Exclusion Criteria:
- Treatment with NSAIDs, clopidogrel, ticlopidine, dipyridamole, warfarin or any other drugs known to affect platelet function
- Ischemic vascular event within the previous 12 months
- Revascularization (angioplasty or coronary by-pass graft surgery) within the previous 12 months
- Platelet count <120 x 10^9/L or >450 x 10^9/L
- For patients without diabetes: fast glucose >7 mmol/L
- Unable to give informed consent
研究計画
研究はどのように設計されていますか？
デザインの詳細
- 観測モデル：コホート
- 時間の展望：見込みのある
この研究は何を測定していますか？
主要な結果の測定
結果測定 |
時間枠 |
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Combined primary endpoint: Cardiovascular death, acute myocardial infarction, ischaemic stroke
時間枠：Evaluation after 3 years
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Evaluation after 3 years
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二次結果の測定
結果測定 |
時間枠 |
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Combined secondary endpoint: Cardiovascular death, acute myocardial infarction, ischaemic stroke
時間枠：Evaluation after 5 years
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Evaluation after 5 years
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Single endpoints:cardiovascular death; acute myocardial infarction; ischemic stroke; stent thrombosis; all-cause death
時間枠：Evaluation after 3 and 5 years
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Evaluation after 3 and 5 years
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その他の成果指標
結果測定 |
メジャーの説明 |
時間枠 |
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Genotype according to pre-specified genetic single nucleotide polymorphisms (SNPs)
時間枠：Baseline
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At the day of blood sampling, plasma samples are retrieved for DNA extraction.
DNA samples are used to evaluate if pre-specified genetic single nucleotide polymorphisms (SNPs) are associated with platelet aggregation levels.
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Baseline
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協力者と研究者
スポンサー
捜査官
- 主任研究者：Anne-Mette Hvas, MD, Ph.D、Department of Clinical Biochemistry, Aarhus University Hospital, Skejby, Denmark
出版物と役立つリンク
一般刊行物
- Nielsen HL, Kristensen SD, Thygesen SS, Mortensen J, Pedersen SB, Grove EL, Hvas AM. Aspirin response evaluated by the VerifyNow Aspirin System and light transmission aggregometry. Thromb Res. 2008;123(2):267-73. doi: 10.1016/j.thromres.2008.03.023. Epub 2008 May 21.
- Pedersen SB, Grove EL, Nielsen HL, Mortensen J, Kristensen SD, Hvas AM. Evaluation of aspirin response by Multiplate whole blood aggregometry and light transmission aggregometry. Platelets. 2009 Sep;20(6):415-20. doi: 10.1080/09537100903100643.
- Hedegaard SS, Hvas AM, Grove EL, Refsgaard J, Rocca B, Davi G, Kristensen SD. Optical platelet aggregation versus thromboxane metabolites in healthy individuals and patients with stable coronary artery disease after low-dose aspirin administration. Thromb Res. 2009 May;124(1):96-100. doi: 10.1016/j.thromres.2008.12.034. Epub 2009 Feb 11.
- Grove EL, Hvas AM, Johnsen HL, Hedegaard SS, Pedersen SB, Mortensen J, Kristensen SD. A comparison of platelet function tests and thromboxane metabolites to evaluate aspirin response in healthy individuals and patients with coronary artery disease. Thromb Haemost. 2010 Jun;103(6):1245-53. doi: 10.1160/TH09-08-0527. Epub 2010 Mar 29.
- Mortensen SB, Larsen SB, Grove EL, Kristensen SD, Hvas AM. Reduced platelet response to aspirin in patients with coronary artery disease and type 2 diabetes mellitus. Thromb Res. 2010 Oct;126(4):e318-22. doi: 10.1016/j.thromres.2010.03.013. Epub 2010 May 7.
- Larsen SB, Neergaard-Petersen S, Grove EL, Kristensen SD, Hvas AM. Increased platelet aggregation and serum thromboxane levels in aspirin-treated patients with prior myocardial infarction. Thromb Haemost. 2012 Jul;108(1):140-7. doi: 10.1160/TH12-01-0026. Epub 2012 Apr 26.
- Wurtz M, Nissen PH, Grove EL, Kristensen SD, Hvas AM. Genetic determinants of on-aspirin platelet reactivity: focus on the influence of PEAR1. PLoS One. 2014 Oct 31;9(10):e111816. doi: 10.1371/journal.pone.0111816. eCollection 2014.
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主要日程の研究
研究開始
一次修了 (実際)
研究の完了 (予想される)
試験登録日
最初に提出
QC基準を満たした最初の提出物
最初の投稿 (見積もり)
学習記録の更新
投稿された最後の更新 (見積もり)
QC基準を満たした最後の更新が送信されました
最終確認日
詳しくは
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