The effect of aspirin dosing on platelet function in diabetic and nondiabetic patients: an analysis from the aspirin-induced platelet effect (ASPECT) study.
OBJECTIVE
Diabetic patients may have a higher prevalence of platelet aspirin resistance than nondiabetic patients. Our goal was to analyze platelet aspirin responsiveness to various aspirin doses in diabetic and nondiabetic patients.


METHODS
We examined the effect of aspirin (81, 162, and 325 mg/day for 4 weeks each) on platelet aspirin responsiveness in 120 stable outpatients (30 diabetic patients and 90 nondiabetic patients) with coronary artery disease (CAD) using light transmittance aggregometry (LTA), VerifyNow, platelet function analyzer (PFA)-100, and levels of urinary 11-dehydro-thromboxane B(2) (11-dh-TxB(2)).


RESULTS
In the total group, a low prevalence (0-2%) of aspirin resistance was observed with all aspirin doses as determined by arachidonic acid-induced LTA. Aspirin resistance was higher at the 81-mg dose in diabetic versus nondiabetic patients using collagen-induced LTA (27 vs. 4%, P = 0.001), VerifyNow (13 vs. 3%, P = 0.05), and urinary 11-dh-TxB(2) (37 vs. 17%, P = 0.03). Diabetic patients treated with 81 mg exhibited higher platelet function measured by VerifyNow, collagen- and ADP-induced LTA, and 11-dh-TxB(2) levels (P <or= 0.02 for all comparisons). Higher aspirin doses significantly inhibited platelet function and decreased aspirin resistance in diabetic patients (P < 0.05).


CONCLUSIONS
Diabetic patients with CAD treated with 81 mg aspirin exhibit a higher prevalence of aspirin resistance and have significantly higher ADP- and collagen-induced platelet aggregation, 11-dh-TxB(2) levels, and aspirin reaction units measured by VerifyNow than nondiabetic patients. Increased aspirin dosing resulted in similar rates of resistance and platelet function levels between groups. These findings indicate that diabetic patients exhibit a global high platelet reactivity phenotype that may be partially overcome by higher aspirin doses.
DiChiara
Joseph
J
Sinai Center for Thrombosis Research, Hoffberger Building, Suite 56, 2401 W. Belvedere Ave., Baltimore, MD 21215, USA.
Bliden
Kevin P
KP
Tantry
Udaya S
US
Hamed
Miruais S
MS
Antonino
Mark J
MJ
Suarez
Thomas A
TA
Bailon
Oscar
O
Singla
Anand
A
Gurbel
Paul A
PA
D000368:Aged; D001241:Aspirin / Q000627:therapeutic use*; D001792:Blood Platelets / Q000187:drug effects / Q000502:physiology*; D003327:Coronary Disease / Q000097:blood* / Q000188:drug therapy; D018592:Cross-Over Studies; D003925:Diabetic Angiopathies / Q000097:blood* / Q000188:drug therapy; D004311:Double-Blind Method; D004351:Drug Resistance; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010974:Platelet Aggregation / Q000187:drug effects; D010975:Platelet Aggregation Inhibitors / Q000627:therapeutic use*; D012016:Reference Values; D013929:Thromboxane B2 / Q000652:urine
D010975:Platelet Aggregation Inhibitors; D013929:Thromboxane B2; D001241:Aspirin