Randomized assessment of ticagrelor versus prasugrel antiplatelet effects in patients with ST-segment-elevation myocardial infarction

Circ Cardiovasc Interv. 2012 Dec;5(6):797-804. doi: 10.1161/CIRCINTERVENTIONS.112.972323. Epub 2012 Nov 20.

Abstract

Background: Ticagrelor and prasugrel provide stronger platelet inhibition compared with clopidogrel. Direct pharmacodynamic comparison between them has not yet been reported in ST-segment-elevation myocardial infarction patients.

Methods and results: In a prospective, single-center, single-blind study, 55 out of 117 (47%) screened consecutive ST-segment-elevation myocardial infarction patients undergoing primary percutaneous coronary intervention were randomized to either ticagrelor 180 mg loading followed by 90 mg bid, or prasugrel 60 mg loading followed by 10 mg od for 5 days. Platelet reactivity (PR) was assessed with the VerifyNow P2Y12 function assay and the Multiplate Analyzer at 0, 1, 2, 6, 24 hours, and 5 days postrandomization. The primary end point, PR with VerifyNow at hour 1, did not differ significantly between patients randomized to ticagrelor versus prasugrel (257.3 P2Y12 reaction unit [PRU], 95% CI 230.8-283.8 versus 231.3 PRU, 95% CI 205.3-257.4; P=0.2). PR did not differ at 2, 6, and 24 hours, although at day 5 it was lower with ticagrelor than prasugrel (25.6 PRU, 95% CI 12.3-38.9 versus 50.3 PRU, 95% CI 36.4-64.1; P=0.01). At hour 2, high on-treatment PR rates (cutoff 208 PRU) were 46.2% and 34.6% for ticagrelor and prasugrel, respectively, decreased significantly thereafter, whereas did not differ significantly between the 2 agents at all the time points of the study.

Conclusions: In patients with ST-segment-elevation myocardial infarction undergoing primary percutaneous coronary intervention, both ticagrelor and prasugrel exhibit an initial delay in the onset of their antiplatelet action. Ticagrelor did not appear superior to prasugrel in reducing PR during the first 24 hours of ST-segment-elevation myocardial infarction.

Clinical trial registration: URL: http://www.clinicaltrials.gov. Unique identifier: NCT01463163.

Publication types

  • Comparative Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine / administration & dosage
  • Adenosine / adverse effects
  • Adenosine / analogs & derivatives*
  • Adenosine / therapeutic use
  • Aged
  • Blood Platelets / drug effects*
  • Blood Platelets / metabolism
  • Drug Administration Schedule
  • Female
  • Greece
  • Humans
  • Least-Squares Analysis
  • Linear Models
  • Male
  • Middle Aged
  • Myocardial Infarction / blood
  • Myocardial Infarction / therapy*
  • Percutaneous Coronary Intervention* / adverse effects
  • Piperazines / administration & dosage
  • Piperazines / adverse effects
  • Piperazines / therapeutic use*
  • Platelet Aggregation / drug effects
  • Platelet Aggregation Inhibitors / administration & dosage
  • Platelet Aggregation Inhibitors / adverse effects
  • Platelet Aggregation Inhibitors / therapeutic use*
  • Platelet Function Tests
  • Prasugrel Hydrochloride
  • Prospective Studies
  • Purinergic P2Y Receptor Antagonists / administration & dosage
  • Purinergic P2Y Receptor Antagonists / adverse effects
  • Purinergic P2Y Receptor Antagonists / therapeutic use*
  • Receptors, Purinergic P2Y12 / drug effects
  • Receptors, Purinergic P2Y12 / metabolism
  • Single-Blind Method
  • Thiophenes / administration & dosage
  • Thiophenes / adverse effects
  • Thiophenes / therapeutic use*
  • Ticagrelor
  • Time Factors
  • Treatment Outcome

Substances

  • P2RY12 protein, human
  • Piperazines
  • Platelet Aggregation Inhibitors
  • Purinergic P2Y Receptor Antagonists
  • Receptors, Purinergic P2Y12
  • Thiophenes
  • Prasugrel Hydrochloride
  • Ticagrelor
  • Adenosine

Associated data

  • ClinicalTrials.gov/NCT01463163