Reduced platelet response to aspirin in patients with coronary artery disease and type 2 diabetes mellitus.
BACKGROUND
Diabetes mellitus is complicated by accelerated atherosclerosis, resulting in an increased risk of coronary artery disease (CAD) and thrombosis. Despite the proven benefits of aspirin, previous studies indicate a reduced cardiovascular protection from aspirin in diabetic patients. We aimed to investigate whether diabetes mellitus influenced the platelet response to aspirin in patients with CAD.


METHODS
Platelet aggregation and activation were evaluated during aspirin treatment in 85 diabetic and 92 non-diabetic patients with CAD. Adherence to aspirin was carefully controlled. All patients had CAD verified by coronary angiography and were taking 75 mg non-enteric coated aspirin daily.


RESULTS
Diabetic patients showed significantly higher levels of platelet aggregation compared to non-diabetic patients evaluated by VerifyNow® Aspirin (p=0.03) and Multiplate® aggregometry using arachidonic acid (AA) 0.5 mM (p=0.005) and 1.0 mM (p=0.009). In addition, platelet activation determined by soluble P-selectin was significantly higher in diabetics compared to non-diabetics (p=0.005). The higher AA-induced aggregation was associated with higher levels of HbA(1c). Compliance was confirmed by low levels of serum thromboxane B(2) (below 7.2 ng/mL). Diabetics had significantly higher levels of serum thromboxane B(2) (p<0.0001).


CONCLUSIONS
Diabetic patients with CAD had significantly higher levels of both platelet aggregation and activation compared to non-diabetic patients with CAD despite treatment with the same dosage of aspirin. These findings may partly explain the reduced cardiovascular protection from aspirin in diabetic patients.
Mortensen
S B
SB
Department of Cardiology, Aarhus University Hospital Skejby, Denmark. sosbm@dadlnet.dk
Larsen
S B
SB
Grove
E L
EL
Kristensen
S D
SD
Hvas
A-M
AM
D000368:Aged; D001241:Aspirin / Q000494:pharmacology / Q000627:therapeutic use*; D003324:Coronary Artery Disease / Q000150:complications* / Q000188:drug therapy*; D003924:Diabetes Mellitus, Type 2 / Q000150:complications*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D015539:Platelet Activation / Q000187:drug effects*; D010974:Platelet Aggregation / Q000187:drug effects*; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*
D010975:Platelet Aggregation Inhibitors; D001241:Aspirin