title: Effects of Ticagrelor Versus Clopidogrel in Troponin-Negative Patients With Low-Risk ACS Undergoing Ad Hoc PCI.
abstract: BACKGROUND
  Many low-risk acute coronary syndrome (ACS) patients are not pre-treated with a P2Y12 receptor inhibitor, and percutaneous coronary interventions (PCIs) are often performed on an ad hoc basis in this population. Pharmacodynamic (PD) studies comparing ticagrelor versus clopidogrel in patients undergoing ad hoc PCI are lacking.
  
  
  OBJECTIVE
  This study sought to assess PD effects of ticagrelor versus clopidogrel loading dose (LD) in the peri-procedural period among troponin-negative ACS patients undergoing ad hoc PCI.
  
  
  METHODS
  This was a prospective, open-label, randomized, multicenter, parallel-group, phase IV PD study. One hundred P2Y12 inhibitor-naïve patients presenting with biomarker-negative ACS and undergoing ad hoc PCI, on a background of aspirin therapy, were randomized to receive either ticagrelor 180 mg LD or clopidogrel 600 mg LD. Platelet reactivity (P2Y12 reaction units [PRU]; VerifyNow assay) was measured at 5 time points: pre-LD, at 0.5, 2, and 8 h post-LD, and at end of PCI. The primary endpoint was PRU levels 2 h post-LD; secondary endpoints included PRU levels at all other time points and inhibition of platelet aggregation; an exploratory analysis evaluated rates of high on-treatment platelet reactivity (HPR) (PRU >208).
  
  
  RESULTS
  At 2 h, PRU levels were significantly lower with ticagrelor versus clopidogrel (98.4 ± 95.4 vs. 257.5 ± 74.5; p < 0.001; primary endpoint). PRU levels diverged as early as 0.5 h post-LD, with significant differences observed by the end of PCI (mean 0.6 h post-LD) and maintained up to 8 h post-LD. HPR rates were also significantly reduced with ticagrelor compared with clopidogrel at the end of PCI (p = 0.030), and at 2 h (p < 0.001) and 8 h (p < 0.001) after LD.
  
  
  CONCLUSIONS
  In low-risk ACS patients undergoing ad hoc PCI, ticagrelor LD provides more prompt and potent platelet inhibition, and lower HPR rates, compared with clopidogrel LD. (Ad Hoc Percutaneous Coronary Intervention Study in Acute Coronary Syndrome Patients: NCT01603082).
authors: University of Florida College of Medicine-Jacksonville, Jacksonville, Florida.
authors: Dominick J
authors: DJ
authors: Angiolillo
authors: University of Florida College of Medicine-Jacksonville, Jacksonville, Florida.
authors: Francesco
authors: F
authors: Franchi
authors: MedStar Washington Hospital Center, Washington, DC.
authors: Ron
authors: R
authors: Waksman
authors: Icahn School of Medicine at Mount Sinai, New York, New York.
authors: Joseph M
authors: JM
authors: Sweeny
authors: University of Minnesota Medical School, Minneapolis, Minnesota.
authors: Ganesh
authors: G
authors: Raveendran
authors: AstraZeneca, Wilmington, Delaware.
authors: Renli
authors: R
authors: Teng
authors: AstraZeneca, Wilmington, Delaware.
authors: Yonggang
authors: Y
authors: Zhao
authors: AstraZeneca, Wilmington, Delaware.
authors: Glenn
authors: G
authors: Carlson
authors: AstraZeneca, Wilmington, Delaware.
authors: Naeem
authors: N
authors: Khan
authors: Icahn School of Medicine at Mount Sinai, New York, New York. Electronic address: roxana.mehran@mountsinai.org.
authors: Roxana
authors: R
authors: Mehran
mesh_terms: D054058:Acute Coronary Syndrome / Q000097:blood / Q000628:therapy*; D000241:Adenosine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D000284:Administration, Oral; D000368:Aged; D000077144:Clopidogrel; D004305:Dose-Response Relationship, Drug; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D062645:Percutaneous Coronary Intervention / Q000379:methods*; D010974:Platelet Aggregation / Q000187:drug effects; D010975:Platelet Aggregation Inhibitors / Q000008:administration & dosage / Q000493:pharmacokinetics; D010979:Platelet Function Tests; D011300:Preoperative Care / Q000379:methods*; D011446:Prospective Studies; D058921:Purinergic P2Y Receptor Antagonists / Q000008:administration & dosage / Q000493:pharmacokinetics; D000077486:Ticagrelor; D013988:Ticlopidine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D016896:Treatment Outcome; D014336:Troponin / Q000097:blood*
chemical_list: D010975:Platelet Aggregation Inhibitors; D058921:Purinergic P2Y Receptor Antagonists; D014336:Troponin; D000077144:Clopidogrel; D000077486:Ticagrelor; D000241:Adenosine; D013988:Ticlopidine
keywords: cardiovascular diseases; coronary artery disease; platelet aggregation inhibitors; platelet function tests; platelet reactivity