Half-dose ticagrelor versus high-dose clopidogrel in reducing platelet reactivity in acute coronary syndrome patients with high on-clopidogrel platelet reactivity (divide study)

Eur J Clin Pharmacol. 2019 Aug;75(8):1059-1068. doi: 10.1007/s00228-019-02687-0. Epub 2019 May 12.

Abstract

Purpose: High on-treatment platelet reactivity (HTPR) after clopidogrel administration in patients with acute coronary syndrome (ACS) has been associated with an increased risk of adverse events. Our previous studies reported that half-dose ticagrelor provides a similar inhibitory effect on adenosine diphosphate (ADP)-induced platelet aggregation as standard-dose ticagrelor, but half-dose of ticagrelor has not been studied in Chinese ACS patients with HTPR. This study aimed to compare the antiplatelet action of half-dose ticagrelor with high-dose clopidogrel in ACS patients with HTPR.

Methods: In this single-center randomized controlled trial, 80 (of 418 screened, 19.13%) ACS patients with HTPR while on clopidogrel were randomized to either half-dose ticagrelor (90 mg LD, then 45 mg twice daily) or high-dose clopidogrel (150 mg once daily). Platelet function was assessed by thromboelastography (TEG) and light transmission aggregometry (LTA), and adverse events were monitored throughout the study for 30 days.

Results: The ADP-induced platelet inhibition rate (IR) as measured by TEG was significantly higher for half-dose ticagrelor compared with high-dose clopidogrel (70.40% [61.10%-91.70%] vs. 44.25% [34.67%-79.07%], p = 0.001). The repeated HTPR rate was dramatically higher for high-dose clopidogrel compared with half-dose ticagrelor (6 of 32, 18.75% vs. 1 of 35, 2.85%; p = 0.04). No patients in either treatment group exhibited a major bleeding event or other adverse events.

Conclusions: In ACS patients with HTPR, half-dose ticagrelor is more effective than high-dose clopidogrel in reducing platelet reactivity (NCT03062462).

Keywords: ACS; Clopidogrel; HTPR; Ticagrelor.

Publication types

  • Randomized Controlled Trial

MeSH terms

  • Acute Coronary Syndrome / blood
  • Acute Coronary Syndrome / drug therapy*
  • Aged
  • Asian People
  • Clopidogrel / administration & dosage*
  • Clopidogrel / adverse effects
  • Dose-Response Relationship, Drug
  • Female
  • Hemorrhage / chemically induced
  • Hemorrhage / epidemiology
  • Humans
  • Male
  • Middle Aged
  • Platelet Activation / drug effects
  • Platelet Aggregation / drug effects
  • Platelet Aggregation Inhibitors / administration & dosage*
  • Platelet Aggregation Inhibitors / adverse effects
  • Platelet Function Tests
  • Ticagrelor / administration & dosage*
  • Ticagrelor / adverse effects
  • Treatment Outcome

Substances

  • Platelet Aggregation Inhibitors
  • Clopidogrel
  • Ticagrelor

Associated data

  • ClinicalTrials.gov/NCT03062462