Abstract 9933: Impact of Antiplatelet Therapy in Patients With Impaired Glucose Tolerance

Abstract

Background: Patients with diabetes mellitus (DM) have reduced clopidogrel-induced antiplatelet effects and increased rates of high platelet reactivity (HPR) compared with non-DM patients. Although approximately 40% of patients with coronary artery disease (CAD) have a pre-diabetic status characterized by impaired glucose tolerance (IGT). However, the impact of IGT on pharmacodynamic (PD) response to antiplatelet therapy is unknown. Objectives: To investigate the impact of IGT on PD response to antiplatelet therapy in patients with IGT. Methods: A 75g oral glucose tolerance test was performed in 52 stable CAD patients treated with maintenance aspirin and clopidogrel therapy. Blood samples were collected at 3 time-points (baseline, 1 and 2 hours after glucose load). IGT was defined as fasting plasma glucose of 110-126 mg/dl and 2 hour plasma glucose of 140-200 mg/dl. Platelet aggregation was assessed by light transmittance aggregometry using 5 and 20 μmol/L ADP stimuli. HPR rates was defined when both maximal aggregation was ≥ 59% with 20 μmol/L ADP and ≥ 46% with 5 μmol/L ADP. Results: There were 22 subjects (42%) who had IGT. At baseline, patients with IGT showed increased platelet reactivity at 5 μmol/L ADP (45.3±13.7 vs 38.6±13.4; p=0.09) and 20 μmol/L ADP stimuli (57.6±12.6 vs 47.5±14.3; p=0.01), and higher HPR rates (54.5% vs 16.0%; p=0.01) compared with non-IGT patients. Similar results were obtained at 1 hour [5 μmol/L ADP (43.1±13.7 vs 36.4±13.9; p=0.1), 20 μmol/L ADP (55.2±12.2 vs 45.4±14.3: p=0.01), HPR rates (36.4% vs 12.5%; p=0.08)], and 2 hours [5 μmol/L ADP (40.7±14.9 vs 35.8±13.9; p=0.2), 20 μmol/L ADP (52.5±12.4 vs 44.4±13.8: p=0.04), HPR rates (40.9% vs 8.3%; p=0.01)]. Conclusions: Patients with IGT on dual antiplatelet therapy with aspirin and clopidogrel have enhanced platelet reactivity and increased rates of high platelet reactivity compared with non-IGT patients, suggesting platelet dysfunction which is independent of hyperglycemia may exist in pre-diabetic patients.