Ticagrelor 60 and 90 mg Doses Achieve Similar Peak Levels of Platelet Inhibition

Ticagrelor 60 mg achieved comparable levels of peak and trough platelet inhibitions as ticagrelor 90 mg in patients with prior myocardial infarction (MI), according to results of a PEGASUS-TIMI 54 substudy.

In the original PEGASUS-TIMI 54 (Prevention of Cardiovascular Events in Patients with Prior Heart Attack Using Ticagrelor Compared to Placebo on a Background of Aspirin-Thrombolysis in Myocardial Infarction 54) study, investigators compared  ticagrelor at 90 mg twice a day and 60 mg twice a day for the prevention of ischemic events in patients with prior MI.

The substudy, published in the Journal of the American College of Cardiology, was designed to examine pharmacokinetic and pharmacodynamic data.

Researchers enrolled 180 patients from the original study who received more than 4 weeks of medication. Patients had blood sampled in the morning before the maintenance dose, and again 2 hours after the dose. All patients received aspirin.

The average plasma levels before and after ticagrelor administration were 35% lower with 60 mg and 38% lower with 90 mg. Both doses achieved high levels of platelet inhibition pre- and post-dose, although there was more variability with the 60 mg dose. The average pre-dose P2Y₁₂ reaction unit values were 59 ± 63 for ticagrelor 60 mg and 47 ± 43 for ticagrelor 90 mg (P=.34).

High platelet reactivity, which was defined as P2Y₁₂ reaction units >208, was rare among patients before the 60-mg dose, and was absent post-dose. Researchers also measured platelet reactivity before and after the dose with light transmittance aggregometry or vasodilator-stimulated phosphoprotein assays, and found that the reactivity was not significantly lower with the 90 mg dose compared with the 60 mg dose. They also noted that aspirin response was not affected by either dose.

Pharmacokinetic results revealed levels of ticagrelor in the 60-mg group at two-thirds of the ticagrelor levels in the 90-mg group, which was expected based on previous studies, according to the researchers.

“Most intriguing was the similar mean platelet P2Y₁₂ inhibition achieved with ticagrelor 60 and 90 mg [twice a day],” they wrote. “This was unexpected, as it had been intended to achieve a lower level of platelet inhibition with the 60-mg regimen, but the observed similarity in platelet inhibition between the 2 ticagrelor groups is entirely consistent with the efficacy results in the main trial being almost identical with ticagrelor 60 and 90 mg [twice a day] compared with placebo.”

“These observations call for further investigation of the safety and efficacy of 60 mg [twice a day] dosing of ticagrelor in other clinical settings associated with atherothrombosis,” researchers concluded.

Reference

Storey RF, Angiolillo DJ, Bonaca MP, et al. Platelet inhibition with ticagrelor 60 mg versus 90 mg twice daily in the PEGASUS-TIMI 54 trial. J Am Coll Cardiol. 2016;67(10):1145-1154. doi: 10.1016/j.jacc.2015.12.062.