The effect of doubling the dose of acetylsalicylic acid (ASA) on platelet function parameters in patients with type 2 diabetes and platelet hyperreactivity during treatment with 75 mg of ASA: a subanalysis of the AVOCADO study

Background: Individuals with diabetes are at 2- to 4-fold higher risk of cardiovascular disease than those without diabetes. High platelet reactivity (HPR) plays a pivotal role in atherothrombotic complications of diabetes. Polish and American diabetes associations recommend treating high-risk diabetic patients with low doses of acetylsalicylic acid (ASA) in primary and secondary prevention of cardiovascular events. Unfortunately, some patients show HPR despite treatment with ASA. Aim: To determine the effect of doubling the dose of ASA on platelet reactivity in patients with type 2 diabetes and HPR despite treatment of with 75 mg of ASA. Methods: 304 type 2 diabetes patients treated with 75 mg of ASA were enrolled into the prospective, randomised, open-label Aspirin Versus/Or Clopidogrel in Aspirin-resistant Diabetics inflammation Outcomes (AVOCADO) study. Platelet reactivity was assessed by Platelet Function Analyser (PFA)-100 (R), VerifyNow (R) Aspirin Assay, and serum thromboxane B-2 (sTXB(2)) and urinary 11-dehydrothromboxane B-2 (u11dhTXB(2)) level measurements. Patients with HPR determined by collagen/epinephrine-induced closure time (CEPI-CT) measured by PFA-100 (R) were randomised in a 2:3 ratio to receive 150 mg of ASA (Group 1) or 75 mg of clopidogrel (Group 2), respectively. Platelet reactivity was assessed at baseline and after 8 weeks of treatment. Results: Complete clinical data and blood samples were ultimately available for 260 of 304 patients initially enrolled to the study. Subsequently, six patients were excluded from the analysis based on suspected ASA non-compliance (sTXB(2) level > 7200 pg/mL). Among 254 patients finally included into analysis, HPR was found in 90 (35.4%) patients of whom 38 patients were randomised to Group 1 and 52 patients to Group 2. Doubling the dose of ASA resulted in a significant CEPI-CT prolongation (Delta 111 s, p < 0.001) and reduction of sTXB(2) level (Delta -101.3 pg/mL, p = 0.001) but did not significantly affect results of other platelet function tests. Conclusions: Doubling the dose of ASA improved platelet reactivity in patients with type 2 diabetes and HPR.