Evaluation of response to antiplatelet therapy using a score based on microRNA and platelet distribution width
Antiplatelet therapy is the cornerstone in preventing thrombotic events in cardiovascular patients. The response, however, to these drugs exhibits large interindividual varibility, and as many as 25% of patients are expected to have insufficient effect of the treatment.
In this research project we will optimize and validate a newly developed laboratory test, which has shown promising results in relation to routinely assessment of the antiplatelet effect of aspirin.
Aspirin is a widely used drug for prevention of thrombotic events in cardiovascular patients, but approximately 25% of patients experience insufficient platelet inhibition due to aspirin, and remain in risk of cardiovascular events despite antiplatelet therapy. Clopidogrel is an ADP-receptor antagonist used alone or in combination with aspirin. As with aspirin, the response to Clopidogrel exhibits large interindividual variability, and approximately one third of patients will have poor antiplatelet effect of the drug. Laboratory tests exist to provide information on platelet function, but these are rather time consuming, analysis has to be performed within a specific time interval from blood sampling and there is a lack of standardization. In daily clinical praxis, this means that testing is not performed.
We have recently developed a simple test of the antiplatelet action of aspirin that is applicable in a routine laboratory setting. The test evaluate the in vivo platelet activity, and is potentially superior to existing in vitro platelet function tests, in relation to access the antiplatelet effect of aspirin. Therefore, the main objective of this research projekt is to optimize and validate the new test as a potential rutinely used biomarker of the individual antiplatelet effect of aspirin. Furthermore, it will be evaluated if the new test may also be a marker of the antiplatelet effect of clopidogrel.
First, an internal temporal validation will be performed in a cohort of patients with intermittent claudication using aspirin, which is the patient category originally used to develop the new test.
Then, an external validation of the test, is performed in a sub-cohort from a population based multicenter study "The Danish Cardiovascular Screening (DANCAVAS) Trial". The sub-cohort consists of participants who are enrolled in the DANCAVAS study at Vejle Hospital, and who are using aspirin at the time of enrollment. Finally, patients in the claudication cohort with an inadequate response to aspirin are perscribed clopidogrel, and inrolled in a new cohort to investigate the performance of the new test in relation til the effect of clopidogrel.
Description of the cohort
The cohort exists of 209 patients with Intermittent Claudiocation using aspirin.
40 % women and 60 % men, with a median age of 71 years.
79 of the patients had their medication changed from aspirin to clopidogrel.
Active cancer, surgery or blood transfusion within 30 days of inclusion, antiplatelet thearpy other than aspirin.
Data and biological material
A questionnare on life style and medical history
Weight, height and ankle brachial index (ABI)
Hematology and lipid parameters
Platelet function tests:
- arachidonic stimulated aggregation while on aspirin (209 patients)
- adenosine stimultated aggregation after two weeks on clopidogrel (79 patients)
Levels of microRNA-92a in platelet-poor plasma
Material in biobank:
serum, EDTA plasma, citrate plasma, heparin plasma, platelet-poor EDTA plasma, buffy coat
Collaborating researchers and departments
Biochemistry and Immunology, Lillebaelt Hospital
- Biochemist Helle Glud Binderup, PhD-student
- Associate professor consultant Jonna Skov Madsen, PhD
- Consultant Claus Lohman Brasen
Department of vascular surgery, Lillebaelt Hospital, Kolding
- Professor, consultant Kim Houlind, PhD