Aspirin Response in High Risk Patients With Coronary Artery Disease

Coronary Artery Disease Clinical Trial

Official title:

Is a Reduced Biochemical Response to Aspirin Associated With Increased Cardiovascular Morbidity and Mortality in High Risk Patients With Coronary Artery Disease?

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT01383304
• Other study ID #: 22527
• Status: Active, not recruiting
• Phase: N/A
• First received: June 22, 2011
• Last updated: May 11, 2016
• Start date: November 2007
• Est. completion date: January 2017

Study information

• Verified date: May 2015
• Source: University of Aarhus
• Contact: n/a
• Is FDA regulated: No
• Health authority: Denmark: The Regional Committee on Biomedical Research EthicsDenmark: Danish Dataprotection Agency
• Study type: Observational

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 906
• Est. completion date: January 2017
• Est. primary completion date: January 2011
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

Observational Model: Cohort, Time Perspective: Prospective

Related Conditions & MeSH terms

• Coronary Artery Disease
• Coronary Disease
• Diabetes Mellitus
• Myocardial Infarction
• Myocardial Ischemia
• Renal Insufficiency
• Renal Insufficiency, Chronic

Locations

Country	Name	City	State
Denmark	Department of Clinical Biochemistry, Aarhus University Hospital, Skejby	Aarhus N

Sponsors (3)

Lead Sponsor	Collaborator
University of Aarhus	Aarhus University Hospital Skejby, Danish Heart Foundation

Country where clinical trial is conducted

Denmark, 

References & Publications (6)

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. — View Citation

Hedegaard SS, Hvas AM, Grove EL, Refsgaard J, Rocca B, Daví 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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Genotype according to pre-specified genetic single nucleotide polymorphisms (SNPs)	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.	Baseline	No
Primary	Combined primary endpoint: Cardiovascular death, acute myocardial infarction, ischaemic stroke		Evaluation after 3 years	No
Secondary	Combined secondary endpoint: Cardiovascular death, acute myocardial infarction, ischaemic stroke		Evaluation after 5 years	No
Secondary	Single endpoints:cardiovascular death; acute myocardial infarction; ischemic stroke; stent thrombosis; all-cause death		Evaluation after 3 and 5 years	No