title: 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.
  
  
  RESULTS
  Patients randomized (1:1) to receive ticagrelor 180 mg LD or clopidogrel 600 mg LD were assessed by diabetic status. Platelet reactivity (P2Y12reaction 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.
  
  
  BACKGROUND
  URL: http://www.clinicaltrials.gov. Unique identifier: NCT01603082.
authors.affiliation: Icahn School of Medicine at Mount Sinai, New York, NY joseph.sweeny@mountsinai.org.
authors.forename: Joseph M
authors.initials: JM
authors.lastname: Sweeny
authors.affiliation: University of Florida College of Medicine-Jacksonville, Jacksonville, FL.
authors.forename: Dominick J
authors.initials: DJ
authors.lastname: Angiolillo
authors.affiliation: University of Florida College of Medicine-Jacksonville, Jacksonville, FL.
authors.forename: Francesco
authors.initials: F
authors.lastname: Franchi
authors.affiliation: University of Florida College of Medicine-Jacksonville, Jacksonville, FL.
authors.forename: Fabiana
authors.initials: F
authors.lastname: Rollini
authors.affiliation: MedStar Washington Hospital Center, Washington, DC.
authors.forename: Ron
authors.initials: R
authors.lastname: Waksman
authors.affiliation: University of Minnesota Medical School, Minneapolis, MN.
authors.forename: Ganesh
authors.initials: G
authors.lastname: Raveendran
authors.affiliation: Icahn School of Medicine at Mount Sinai, New York, NY.
authors.forename: George
authors.initials: G
authors.lastname: Dangas
authors.affiliation: AstraZeneca, Wilmington, DE.
authors.forename: Naeem D
authors.initials: ND
authors.lastname: Khan
authors.affiliation: AstraZeneca, Wilmington, DE.
authors.forename: Glenn F
authors.initials: GF
authors.lastname: Carlson
authors.affiliation: AstraZeneca, Wilmington, DE.
authors.forename: Yonggang
authors.initials: Y
authors.lastname: Zhao
authors.affiliation: AstraZeneca, Wilmington, DE.
authors.forename: Renli
authors.initials: R
authors.lastname: Teng
authors.affiliation: Icahn School of Medicine at Mount Sinai, New York, NY.
authors.forename: Roxana
authors.initials: R
authors.lastname: Mehran
mesh_terms: D054058:Acute Coronary Syndrome / Q000097:blood / Q000453:epidemiology / Q000628:therapy*; D000241:Adenosine / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D000368:Aged; D001792:Blood Platelets / Q000187:drug effects*; D000077144:Clopidogrel; D015897:Comorbidity; D003920:Diabetes Mellitus / Q000453:epidemiology*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D062645:Percutaneous Coronary Intervention / Q000379:methods*; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D016032:Randomized Controlled Trials as Topic; D000077486:Ticagrelor; D013988:Ticlopidine / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D014336:Troponin / Q000097:blood
chemical_list: D010975:Platelet Aggregation Inhibitors; D014336:Troponin; D000077144:Clopidogrel; D000077486:Ticagrelor; D000241:Adenosine; D013988:Ticlopidine
keywords: ad hoc percutaneous coronary intervention; clopidogrel; diabetes mellitus; platelet reactivity; ticagrelor