Clinical trial NCT01383304: Aspirin Response in High Risk Patients With Coronary Artery Disease
Official title: Is a Reduced Biochemical Response to Aspirin Associated With Increased Cardiovascular Morbidity and Mortality in High Risk Patients With Coronary Artery Disease?
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Coronary Artery Disease
Myocardial Infarction
Diabetes Mellitus
Renal Insufficiency, Chronic
Keywords: Platelet aggregation
Aspirin
Drug resistance
Thromboxane B2
Pharmacologic Actions
Platelet Aggregation Inhibitors
Lead sponsor: University of Aarhus
Sponsor class: OTHER
Collaborators: name: Aarhus University Hospital Skejby
name: Danish Heart Foundation
First posted: 2011-06-28
Enrollment: 906
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: 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.

Brief 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.


Eligibility criteria: 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

Primary outcomes:
measure: Combined primary endpoint: Cardiovascular death, acute myocardial infarction, ischaemic stroke
timeFrame: Evaluation after 3 years
Secondary outcomes:
measure: Combined secondary endpoint: Cardiovascular death, acute myocardial infarction, ischaemic stroke
timeFrame: Evaluation after 5 years
measure: Single endpoints:cardiovascular death; acute myocardial infarction; ischemic stroke; stent thrombosis; all-cause death
timeFrame: Evaluation after 3 and 5 years
Other outcomes:
measure: Genotype according to pre-specified genetic single nucleotide polymorphisms (SNPs)
timeFrame: Baseline
Locations:
city: Aarhus N
country: Denmark
facility: Department of Clinical Biochemistry, Aarhus University Hospital, Skejby
Study officials:
affiliation: Department of Clinical Biochemistry, Aarhus University Hospital, Skejby, Denmark
name: Anne-Mette Hvas, MD, Ph.D
role: PRINCIPAL_INVESTIGATOR
References:
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.
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.
citation: 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.
citation: 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.
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.
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. Epub 2012 Apr 26.
citation: 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.