Background: Reduced clopidogrel- and aspirin-induced platelet inhibition has been described in patients with type 2 diabetes mellitus (T2DM) compared to non-diabetic patients, especially in those with poor glycaemic control. However, whether optimizing glycaemic control in such patients may reduce platelet reactivity and improve responsiveness to antiplatelet agents has not been evaluated to date.
Purpose: To investigate the impact of improving glycaemic control on platelet reactivity in patients with T2DM and coronary artery disease (CAD) receiving dual antiplatelet therapy with aspirin and clopidogrel.
Methods: Prospective pharmacodynamic (PD) investigation with a before and after design conducted in patients with T2DM with poor glycemic control and CAD treated with aspirin and clopidogrel. Glycosylated hemoglobin (HbA1c) of ≥7.5% was considered poor glycemic control. Patients were included in a specific optimization program of 4 months duration. The program was based on lifestyle and dietary instructions and adjustment of hypoglycemic treatment in the Endocrine Unit outpatient clinic. Blood samples were collected at baseline and at the end of the program in order to assess both metabolic status and platelet reactivity. Platelet function tests performed included: a) Light Transmittance Aggregometry (LTA) using ADP 5 (primary endpoint) and 20mmol, arachidonic acid (AA) and collagen as agonists; b) VASP analysis; c) Multiple electrode aggregometry (MEA) using ADP and AA as agonists; and d) The VerifyNow (VN) system.
Results: A total of 37 patients with valid PD data were included. Mean HbA1c levels were improved during the study (baseline: 8.5±0.2% vs. end of the program: 7.4±0.2%; p<0.001), as well as other glycaemic parameters of metabolic control, such as preprandial and peak postprandial blood glucose, and glucose variability (maximum amplitude of glycaemic excursion, MAGE). The optimization of glycaemic control was not reflected in an improvement in responsiveness to clopidogrel or aspirin. In particular, no differences were observed in platelet reactivity before and after the program as measured with LTA ADP 5mmol (36.0±2.2% vs. 36.6±2.0%; p=0.760) or any of the other platelet function tests (Figure) or agonists employed. No significant differences were observed in exploratory subgroup analyses stratifying patients according to the following variables (dichotomizing when standard cutoff values applied and/or per quartiles): duration of T2DM (<10 vs. ≥10 years), HbA1c, preprandial capillary blood glucose, peak postprandial capillary blood glucose, and MAGE.
Conclusions: Optimization of glycaemic control in patients with T2DM and CAD did not result in a short-term improvement on clopidogrel- or aspirin-mediated platelet inhibition.