Antiplatelet Effect of Different Loading Doses of Ticagrelor in Patients With Non-ST-Elevation Acute Coronary Syndrome Undergoing Percutaneous Coronary Intervention: The APELOT Trial

Can J Cardiol. 2017 Dec;33(12):1675-1682. doi: 10.1016/j.cjca.2017.09.002. Epub 2017 Sep 12.

Abstract

Background: We hypothesized that a high ticagrelor loading dose (LD) may improve platelet inhibition in patients with non-ST-elevation acute coronary syndrome (NSTE-ACS) undergoing percutaneous coronary intervention (PCI).

Methods: This interventional multicentre open-label trial randomized 278 patients with NSTE-ACS to a high (360 mg) or conventional (180 mg) ticagrelor LD. The primary outcome was the platelet reactivity index (PRI) 1 hour after administration of the LD. Secondary outcomes included PRI at 0.5 hour, 1 hour, 8 hours, and 24 hours; periprocedural myocardial infarction (PMI); major cardiac adverse events; and bleeding events.

Results: Two hundred sixty-two patients completed the major end points. PRI was lower in the high-LD group than in the conventional-LD group at any time point (all, P < 0.05), including at 1 hour (12.2% vs 16.7%; P = 0.023). At 0.5 hour, the high-LD group showed a lower high-platelet reactivity rate (49.6% vs 60.2%; P = 0.013) and a higher low-platelet reactivity rate (24.8% vs 12.8%; P = 0.017) than did the conventional LD group. No significant differences in the bleeding rates were found between the 2 groups (14% vs 14.3%). Four cases of PMI and 1 death in each group, as well as 1 acute myocardial infarction in the conventional LD group, occurred. There was no stroke, target lesion revascularization, or target vessel revascularization.

Conclusions: Doubling the ticagrelor LD achieved faster onset and greater platelet inhibition without an increase in adverse events in patients with NSTE-ACS undergoing PCI.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial

MeSH terms

  • Acute Coronary Syndrome / blood
  • Acute Coronary Syndrome / drug therapy*
  • Acute Coronary Syndrome / surgery
  • Adenosine / administration & dosage
  • Adenosine / analogs & derivatives*
  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Dose-Response Relationship, Drug
  • Electrocardiography*
  • Female
  • Follow-Up Studies
  • Humans
  • Male
  • Middle Aged
  • Percutaneous Coronary Intervention*
  • Platelet Activation / drug effects
  • Platelet Aggregation / drug effects*
  • Platelet Function Tests
  • Prospective Studies
  • Purinergic P2Y Receptor Antagonists / administration & dosage
  • Ticagrelor
  • Treatment Outcome
  • Young Adult

Substances

  • Purinergic P2Y Receptor Antagonists
  • Ticagrelor
  • Adenosine