Consistent platelet inhibition with ticagrelor 60 mg twice-daily following myocardial infarction regardless of diabetes status

Thromb Haemost. 2017 May 3;117(5):940-947. doi: 10.1160/TH16-09-0703. Epub 2017 Mar 16.

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.

Trial registration: ClinicalTrials.gov NCT01225562.

Keywords: Coronary artery disease; acute coronary syndromes; pharmacodynamics; pharmacology.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial

MeSH terms

  • Adenosine / administration & dosage
  • Adenosine / adverse effects
  • Adenosine / analogs & derivatives*
  • Adenosine / pharmacokinetics
  • Aged
  • Biomarkers / blood
  • Blood Platelets / drug effects*
  • Blood Platelets / metabolism
  • Cell Adhesion Molecules / blood
  • Diabetes Mellitus / blood*
  • Diabetes Mellitus / diagnosis
  • Diabetes Mellitus / drug therapy
  • Drug Administration Schedule
  • England
  • Female
  • Florida
  • Glycated Hemoglobin A / metabolism
  • Humans
  • Hypoglycemic Agents / therapeutic use
  • Insulin / therapeutic use
  • Male
  • Microfilament Proteins / blood
  • Middle Aged
  • Myocardial Infarction / blood
  • Myocardial Infarction / diagnosis
  • Myocardial Infarction / drug therapy*
  • Phosphoproteins / blood
  • Platelet Activation / drug effects*
  • Platelet Aggregation / drug effects
  • Platelet Aggregation Inhibitors / administration & dosage*
  • Platelet Aggregation Inhibitors / adverse effects
  • Platelet Aggregation Inhibitors / pharmacokinetics
  • Platelet Function Tests
  • Purinergic P2Y Receptor Antagonists / administration & dosage*
  • Purinergic P2Y Receptor Antagonists / adverse effects
  • Purinergic P2Y Receptor Antagonists / pharmacokinetics
  • Receptors, Purinergic P2Y12 / blood
  • Receptors, Purinergic P2Y12 / drug effects
  • Risk Factors
  • Ticagrelor
  • Time Factors
  • Treatment Outcome

Substances

  • Biomarkers
  • Cell Adhesion Molecules
  • Glycated Hemoglobin A
  • Hypoglycemic Agents
  • Insulin
  • Microfilament Proteins
  • P2RY12 protein, human
  • Phosphoproteins
  • Platelet Aggregation Inhibitors
  • Purinergic P2Y Receptor Antagonists
  • Receptors, Purinergic P2Y12
  • hemoglobin A1c protein, human
  • vasodilator-stimulated phosphoprotein
  • Ticagrelor
  • Adenosine

Associated data

  • ClinicalTrials.gov/NCT01225562