Rationale and design of the Hunting for the off-target propertIes of Ticagrelor on Endothelial function and other Circulating biomarkers in Humans (HI-TECH) trial

Am Heart J. 2017 Jul:189:128-136. doi: 10.1016/j.ahj.2017.03.017. Epub 2017 Mar 29.

Abstract

Background: Among the 3 approved oral P2Y12 inhibitors for the treatment for patients with acute coronary syndrome (ACS), ticagrelor, but not prasugrel or clopidogrel, has been associated with off-target properties, such as improved endothelial-dependent vasomotion and increased adenosine plasma levels.

Methods: The HI-TECH study (NCT02587260) is a multinational, randomized, open-label, crossover study with a Latin squares design, conducted at 5 European sites, in which patients free from recurrent ischemic or bleeding events ≥30 days after a qualifying ACS were allocated to sequentially receive a 30 ± 5-day treatment with prasugrel, clopidogrel, and ticagrelor in random order. The primary objective was to evaluate whether ticagrelor, at treatment steady state (ie, after 30 ± 5 days of drug administration), as compared with both clopidogrel and prasugrel, is associated with an improved endothelial function, assessed with peripheral arterial tonometry. Thirty-six patients undergoing evaluable endothelial function assessment for each of the assigned P2Y12 inhibitor were needed to provide 90% power to detect a 10% relative change of the reactive hyperemia index in the ticagrelor group.

Conclusion: The HI-TECH study is the first randomized, crossover study aiming to ascertain whether ticagrelor, when administered at approved regimen in post-ACS patients, improves endothelial function as compared with both clopidogrel and prasugrel.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial

MeSH terms

  • Adenosine / administration & dosage
  • Adenosine / analogs & derivatives*
  • Administration, Oral
  • Biomarkers / blood*
  • Cross-Over Studies
  • Dose-Response Relationship, Drug
  • Endothelium, Vascular / drug effects*
  • Endothelium, Vascular / physiopathology
  • Female
  • Follow-Up Studies
  • Graft Occlusion, Vascular / physiopathology
  • Graft Occlusion, Vascular / prevention & control*
  • Humans
  • Male
  • Percutaneous Coronary Intervention / adverse effects*
  • Purinergic P2Y Receptor Antagonists / administration & dosage
  • Secondary Prevention / methods*
  • Stents / adverse effects
  • Ticagrelor
  • Treatment Outcome
  • Vasodilation / drug effects
  • Vasodilation / physiology*

Substances

  • Biomarkers
  • Purinergic P2Y Receptor Antagonists
  • Ticagrelor
  • Adenosine