Variability in platelet response to a single daily dose of 150 mg enteric coated aspirin in a high risk population.
OBJECTIVE
Previous studies have reported inadequate anti-platelet effect in 0.4-35% of patients taking aspirin. Such studies have arbitrarily defined the terms "semi-responders", "non-responders" or "resistant" to variable doses of aspirin on the basis of absolute values derived from different ex-vivo platelet aggregation (PA) methods. Our objective was to define response to 150-mg dose of aspirin in terms of normally distributed values using an ex-vivo measure of PA in a population at high risk for vascular events.


METHODS
We prospectively studied high risk patients with either established coronary artery disease (CAD) or stroke or transient ischemic attack (TIA) or peripheral vascular disease or with multiple atherothrombotic risk factors like diabetes plus one of the following-- hypertension, increased total cholesterol, cigarette smoking, micro-albuminuria, low-high density lipoprotein (HDL), family history of CAD and receiving single 150 mg dose of aspirin daily. PA was assessed by chronolog lumi-aggregometer (490-2D) using arachidonic acid (AA) reagent.


RESULTS
130 patients were studied. The response of subjects to aspirin followed a normal, bell shaped distribution curve with a mean and standard deviation (S.D.) of 13.1 +/- 4.4%. 3.1% patients had PA values more than 2 S.D. of the mean, hence termed as hypo-responders to aspirin while another 3.1% patients had PA values less than 2 S.D. of the mean, hence termed as hyper-responders to aspirin.


CONCLUSIONS
There is minimal inter-individual variability in the response to aspirin when tested with AA as the reagent. The response to aspirin follows a normal Gaussian distribution. The prevalence of hypo-responders to aspirin in high risk population is only 3.1%. This is the first study to document "hypo" and "hyper-responders" to single daily dose of 150 mg aspirin. The clinical relevance of these findings remains to be determined.
Mardikar
H
H
Spandan Heart Institute and Research Center, Nagpur, India.
Deo
D
D
Deshpande
N
N
Mardikar
Manjusha
M
Ghosh
A
A
Munot
Khushboo
K
Steinhubl
S
S
Mukherjee
D
D
D000368:Aged; D001241:Aspirin / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D001760:Bleeding Time / Q000706:statistics & numerical data; D002318:Cardiovascular Diseases / Q000517:prevention & control*; D003906:Developing Countries; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D004351:Drug Resistance; D005260:Female; D006801:Humans; D007194:India; D008297:Male; D008875:Middle Aged; D016011:Normal Distribution; D010974:Platelet Aggregation / Q000187:drug effects*; D010975:Platelet Aggregation Inhibitors / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D011446:Prospective Studies; D012307:Risk Factors; D013608:Tablets, Enteric-Coated
D010975:Platelet Aggregation Inhibitors; D013608:Tablets, Enteric-Coated; D001241:Aspirin