title: Consistent platelet inhibition with ticagrelor 60 mg twice-daily following myocardial infarction regardless of diabetes status.
abstract: Diabetes increases cardiovascular risk and reduces pharmacodynamic response to some oral antiplatelet drugs. This study aimed to determine whether ticagrelor 60 mg twice daily (bid) provided potent and consistent platelet inhibition in patients with vs without diabetes in the PEGASUS-TIMI 54 platelet function substudy. Out of 180 patients studied, 58 patients were randomised to and had received at least four weeks of ticagrelor 60 mg bid, with 20 (34 %) having diabetes, 58 patients received ticagrelor 90 mg bid, with 12 (21 %) having diabetes, and 64 patients received placebo, with 18 (28 %) having diabetes. Blood was sampled pre- and 2 hours post-maintenance dose. In patients treated with ticagrelor 60 mg bid, on-treatment platelet reactivity to ADP, as determined by light transmission aggregometry (LTA), VerifyNow and VASP, was similar in patients with vs without diabetes (LTA post-dose, ADP 20 µM: 29 ± 14 vs 34 ± 10 %, respectively; p = 0.19). A consistent inhibitory effect of ticagrelor 60 mg bid was observed pre- and post-dose regardless of diabetes status, even in insulin-treated patients. Patients with diabetes did not have an increased incidence of high platelet reactivity in either ticagrelor group. Platelet reactivity was similar in patients with diabetes treated with ticagrelor 60 mg vs 90 mg bid. Pharmacokinetics of ticagrelor were not affected by diabetes status. In conclusion, ticagrelor 60 mg bid is equally effective at reducing platelet reactivity in patients with and without diabetes, yielding a consistently high level of platelet inhibition regardless of diabetes status.
authors.forename: Mark R
authors.initials: MR
authors.lastname: Thomas
authors.forename: Dominick J
authors.initials: DJ
authors.lastname: Angiolillo
authors.forename: Marc P
authors.initials: MP
authors.lastname: Bonaca
authors.forename: Ramzi A
authors.initials: RA
authors.lastname: Ajjan
authors.forename: Heather M
authors.initials: HM
authors.lastname: Judge
authors.forename: Fabiana
authors.initials: F
authors.lastname: Rollini
authors.forename: Francesco
authors.initials: F
authors.lastname: Franchi
authors.forename: Arif J
authors.initials: AJ
authors.lastname: Ahsan
authors.forename: Deepak L
authors.initials: DL
authors.lastname: Bhatt
authors.forename: Julia F
authors.initials: JF
authors.lastname: Kuder
authors.forename: Philippe Gabriel
authors.initials: PG
authors.lastname: Steg
authors.forename: Marc
authors.initials: M
authors.lastname: Cohen
authors.forename: Rangasamy
authors.initials: R
authors.lastname: Muthusamy
authors.forename: Marc S
authors.initials: MS
authors.lastname: Sabatine
authors.affiliation: Prof. Robert F. Storey, MD DM FESC, Department of Infection, Immunity and Cardiovascular Disease, University of Sheffield, Beech Hill Road, Sheffield, S10 2RX, UK, E-mail: r.f.storey@sheffield.ac.uk.
authors.forename: Robert F
authors.initials: RF
authors.lastname: Storey
mesh_terms: D000241:Adenosine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D000368:Aged; D015415:Biomarkers / Q000097:blood; D001792:Blood Platelets / Q000187:drug effects* / Q000378:metabolism; D015815:Cell Adhesion Molecules / Q000097:blood; D003920:Diabetes Mellitus / Q000097:blood* / Q000175:diagnosis / Q000188:drug therapy; D004334:Drug Administration Schedule; D004739:England; D005260:Female; D005431:Florida; D006442:Glycated Hemoglobin / Q000378:metabolism; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use; D007328:Insulin / Q000627:therapeutic use; D008297:Male; D008840:Microfilament Proteins / Q000097:blood; D008875:Middle Aged; D009203:Myocardial Infarction / Q000097:blood / Q000175:diagnosis / Q000188:drug therapy*; D010750:Phosphoproteins / Q000097:blood; D015539:Platelet Activation / Q000187:drug effects*; D010974:Platelet Aggregation / Q000187:drug effects; D010975:Platelet Aggregation Inhibitors / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D010979:Platelet Function Tests; D058921:Purinergic P2Y Receptor Antagonists / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D058925:Receptors, Purinergic P2Y12 / Q000097:blood / Q000187:drug effects; D012307:Risk Factors; D000077486:Ticagrelor; D013997:Time Factors; D016896:Treatment Outcome; D000098662:Vasodilator-Stimulated Phosphoprotein
chemical_list: D000241:Adenosine; D015415:Biomarkers; D015815:Cell Adhesion Molecules; D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D007328:Insulin; D008840:Microfilament Proteins; D010750:Phosphoproteins; D010975:Platelet Aggregation Inhibitors; D058921:Purinergic P2Y Receptor Antagonists; D058925:Receptors, Purinergic P2Y12; D000077486:Ticagrelor; D000098662:Vasodilator-Stimulated Phosphoprotein; C548576:P2RY12 protein, human; C517652:hemoglobin A1c protein, human
keywords: Coronary artery disease; acute coronary syndromes; pharmacodynamics; pharmacology