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.
Aperçu de l'étude
Statut
Type d'étude
Inscription (Réel)
Contacts et emplacements
Lieux d'étude
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Aarhus N, Danemark, 8200
- Department of Clinical Biochemistry, Aarhus University Hospital, Skejby
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Critères de participation
Critère d'éligibilité
Âges éligibles pour étudier
Accepte les volontaires sains
Sexes éligibles pour l'étude
Méthode d'échantillonnage
Population étudiée
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.
La description
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
Plan d'étude
Comment l'étude est-elle conçue ?
Détails de conception
- Modèles d'observation: Cohorte
- Perspectives temporelles: Éventuel
Que mesure l'étude ?
Principaux critères de jugement
Mesure des résultats |
Délai |
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Combined primary endpoint: Cardiovascular death, acute myocardial infarction, ischaemic stroke
Délai: Evaluation after 3 years
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Evaluation after 3 years
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Mesures de résultats secondaires
Mesure des résultats |
Délai |
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Combined secondary endpoint: Cardiovascular death, acute myocardial infarction, ischaemic stroke
Délai: 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
Délai: Evaluation after 3 and 5 years
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Evaluation after 3 and 5 years
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Autres mesures de résultats
Mesure des résultats |
Description de la mesure |
Délai |
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Genotype according to pre-specified genetic single nucleotide polymorphisms (SNPs)
Délai: 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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Collaborateurs et enquêteurs
Parrainer
Les enquêteurs
- Chercheur principal: Anne-Mette Hvas, MD, Ph.D, Department of Clinical Biochemistry, Aarhus University Hospital, Skejby, Denmark
Publications et liens utiles
Publications générales
- 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.
Dates d'enregistrement des études
Dates principales de l'étude
Début de l'étude
Achèvement primaire (Réel)
Achèvement de l'étude (Anticipé)
Dates d'inscription aux études
Première soumission
Première soumission répondant aux critères de contrôle qualité
Première publication (Estimation)
Mises à jour des dossiers d'étude
Dernière mise à jour publiée (Estimation)
Dernière mise à jour soumise répondant aux critères de contrôle qualité
Dernière vérification
Plus d'information
Termes liés à cette étude
Mots clés
Termes MeSH pertinents supplémentaires
- Ischémie
- Processus pathologiques
- Nécrose
- Maladies cardiaques
- Maladies cardiovasculaires
- Maladies vasculaires
- Artériosclérose
- Maladies artérielles occlusives
- Maladies rénales
- Maladies urologiques
- Infarctus du myocarde
- Infarctus
- Maladie de l'artère coronaire
- Ischémie myocardique
- Maladie coronarienne
- Insuffisance rénale chronique
- Insuffisance rénale
Autres numéros d'identification d'étude
- 22527
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