Is Aspirin Resistance a Real Problem in People With Type 2 Diabetes?

Response to Sacco et al.

We read with great interest the article by Sacco et al. (1) on the problem of aspirin efficacy in primary prevention of cardiovascular events in type 2 diabetic patients. In our opinion, this is an important yet somewhat understudied area in the field of diabetes care. The Diabetes Prevention Project (DPP) trial has shown lower effects of primary prevention of cardiovascular disease with low-dose aspirin in diabetic subjects compared with nondiabetic subjects. The mechanism(s) of reduced sensitivity of platelets taken from diabetic subjects are not fully understood (2). We conducted a study aimed to evaluate a possible association between the parameters relevant to metabolic control of diabetes and platelet sensitivity to aspirin in blood taken from 31 aspirin-treated, poorly controlled type 2 diabetic patients and 48 healthy volunteers (150 mg/day for a week). Platelets’ ability to adhere and aggregate was determined with a platelet function analyzer (PFA-100), as well as turbidimetric and whole-blood aggregometry, using collagen, ADP, and arachidonic acid as platelet agonists. We found that aspirin reduced platelet reactivity up to sixfold less effectively in diabetic than in control subjects. In the diabetic subjects, the response of platelets to aspirin was inversely associated with HbA_1c and total cholesterol and positively associated with HDL cholesterol (3). These findings support our belief that metabolic control of diabetes contributes to reduced platelet sensitivity to aspirin. Extensive protein glycation may attenuate aspirin’s ability to acetylate target platelet proteins in diabetic patients. Also, lipid disturbances in platelet membranes might substantially contribute to aspirin efficacy (4); notwithstanding, anti-inflammatory actions may also be important in aspirin-mediated reduction of the overall cardiovascular risk. Hence, monitoring of antiplatelet action of aspirin should be considered at least in high-risk patients. There is a need for simple, fast, reliable, and cheap diagnostic methods for this purpose.

To summarize, “aspirin resistance” is a real and clinically important problem, and some people with diabetes might require more intensive treatment to reduce glucose and lipid concentrations and thereby improve platelet response to aspirin. Patients with poorly controlled diabetes may need larger doses of aspirin or an additional antiplatelet agent to avoid thrombotic complications. However, the risk of bleeding must be always balanced against the beneficial cardiovascular effect.