Impact of Diabetes Mellitus on the Pharmacodynamic Effects of Ticagrelor Versus Clopidogrel in Troponin‐Negative Acute Coronary Syndrome Patients Undergoing Ad Hoc Percutaneous Coronary Intervention

Abstract

Background Diabetes mellitus ( DM ) is associated with enhanced platelet reactivity and impaired response to oral antiplatelet therapy, including clopidogrel. This post hoc analysis investigated the pharmacodynamic effects of ticagrelor versus clopidogrel loading dose ( LD ) in troponin‐negative acute coronary syndrome patients with or without DM undergoing percutaneous coronary intervention in the Ad Hoc PCI study. Methods and Results Patients randomized (1:1) to receive ticagrelor 180 mg LD or clopidogrel 600 mg LD were assessed by diabetic status. Platelet reactivity (P2Y 12 reaction units [ PRU ] on VerifyNow ® assay) was measured pre‐ LD , at 0.5, 2, and 8 hours post‐ LD , and at the end of the percutaneous coronary intervention. The primary endpoint was PRU levels 2 hours post‐ LD ; secondary endpoints included rates of high on‐treatment platelet reactivity ( PRU ≥208). Of 100 randomized patients, 51 received ticagrelor ( DM , n=20; non‐ DM , n=31) and 49 clopidogrel ( DM , n=16; non‐ DM , n=33). At 2 hours post‐ LD , mean ( SD ) PRU levels in DM patients were 130.1 (111.7) with ticagrelor versus 287.6 (71.9) with clopidogrel (mean [95% CI ] difference −157.5 [−225.3, −89.8]; P <0.001); in non‐ DM patients, they were 75.3 (75.7) versus 243.0 (72.4) (mean difference −167.7 [−207.1, −128.3]; P <0.001). High on‐treatment platelet reactivity rates at 2 hours post‐ LD were also significantly ( P <0.001) reduced with ticagrelor versus clopidogrel in DM and non‐ DM patients. Between‐treatment differences for PRU and high on‐treatment platelet reactivity were not significant at earlier time points but were at 8 hours post‐ LD ( P <0.001). Conclusions Compared with clopidogrel, ticagrelor achieved faster, enhanced platelet inhibition and reduced high on‐treatment platelet reactivity rates, in DM and non‐ DM patients. Clinical Trial Registration URL : http://www.clinicaltrials.gov . Unique identifier: NCT 01603082.