Ticagrelor vs clopidogrel followed by ticagrelor re-loading in patients with ST-segment elevation myocardial infarction undergoing primary percutaneous coronary intervention: A randomized, pharmacodynamic comparison

Platelets. 2016 Jul;27(5):420-6. doi: 10.3109/09537104.2015.1125874. Epub 2016 Jan 14.

Abstract

Among patients allocated to ticagrelor in the primary percutaneous coronary intervention (PCI) cohort of Platelet Inhibition and Patient Outcomes (PLATO) trial, 40.7% had received pre-randomization 600 mg of clopidogrel. This scenario is frequently employed in real-world practice. In a prospective, three-center, single-blind, parallel design study, 74 P2Y12 inhibitor-naive patients undergoing primary PCI were randomized (Hour 0) to ticagrelor 180 mg loading dose (LD) vs clopidogrel 600 mg LD followed after 2 h by ticagrelor 180 mg re-LD. Platelet reactivity (VerifyNow, in PRU) was assessed at Hour 0, 2, 4, 6, and 24. The primary comparison was non-inferiority of ticagrelor to clopidogrel followed by ticagrelor re-LD regarding platelet reactivity at 24 h using a prespecified margin of <35 PRU for the upper bound of the one-sided 97.5% confidence interval (CI). Ticagrelor was proven non-inferior to clopidogrel followed by ticagrelor re-LD with a difference between arms of 13.5 PRU (28.8 upper 97.5% CI), p = 0.001. At Hour 2, platelet reactivity was lower in ticagrelor only vs clopidogrel followed by ticagrelor re-LD groups with least square estimate mean difference (95% CI) -105.7 (-140.6 to -70.8), p < 0.001, without significant difference thereafter. In conclusion, in patients undergoing primary PCI, a strategy of ticagrelor LD only was proven non-inferior to clopidogrel LD followed by ticagrelor re-LD, in terms of antiplatelet efficacy at 24 h post-randomization and provided an earlier onset of platelet inhibition.

Keywords: Angioplasty; myocardial infarction; pharmacology; platelets.

Publication types

  • Clinical Trial
  • Comparative Study
  • Multicenter Study
  • Randomized Controlled Trial

MeSH terms

  • Adenosine / administration & dosage
  • Adenosine / analogs & derivatives*
  • Adenosine / pharmacokinetics
  • Adenosine / therapeutic use
  • Biomarkers
  • Blood Platelets / drug effects
  • Blood Platelets / metabolism
  • Clopidogrel
  • Electrocardiography
  • Myocardial Infarction / blood
  • Myocardial Infarction / diagnosis*
  • Myocardial Infarction / therapy*
  • Percutaneous Coronary Intervention* / methods
  • Platelet Activation / drug effects
  • Platelet Aggregation Inhibitors / administration & dosage
  • Platelet Aggregation Inhibitors / pharmacokinetics
  • Platelet Aggregation Inhibitors / therapeutic use*
  • Platelet Function Tests
  • Risk Factors
  • Ticagrelor
  • Ticlopidine / administration & dosage
  • Ticlopidine / analogs & derivatives*
  • Ticlopidine / pharmacokinetics
  • Ticlopidine / therapeutic use

Substances

  • Biomarkers
  • Platelet Aggregation Inhibitors
  • Clopidogrel
  • Ticagrelor
  • Adenosine
  • Ticlopidine