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Platelet Inhibition With Ticagrelor 60 mg Versus 90 mg Twice Daily in the PEGASUS-TIMI 54 Trial
- Source :
- Journal of the American College of Cardiology. 67:1145-1154
- Publication Year :
- 2016
- Publisher :
- Elsevier BV, 2016.
-
Abstract
- Background The 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) trial studied 2 doses of ticagrelor, 90 mg twice a day (bid) and 60 mg bid, for long-term prevention of ischemic events in patients with prior myocardial infarction. Both doses similarly reduced the rate of ischemic events versus placebo. The pharmacokinetics and pharmacodynamics of ticagrelor 60 mg bid have not been studied. Objectives In this study, the authors sought to study the pharmacokinetics and pharmacodynamics for ticagrelor 60 mg compared with 90 mg bid. Methods A total of 180 patients who received >4 weeks of study medication had blood sampling in the morning pre-maintenance dose and again 2 h post-dose. All patients received aspirin. Plasma levels of ticagrelor and its active metabolite AR-C124910XX were determined. P2Y12 inhibition was assessed by the VerifyNow P2Y12 assay (Accumetrics, Inc., San Diego, California) (P2Y12 reaction units [PRU]), light transmittance aggregometry (adenosine diphosphate 5 and 20 ÎĽmol/l and arachidonic acid), and vasodilator-stimulated phosphoprotein phosphorylation assays. VerifyNow Aspirin assays and serum thromboxane B2 measurements were performed. Results Mean pre- and post-dose plasma levels of ticagrelor were 35% and 38% lower, respectively, with 60 mg versus 90 mg. Both doses achieved high levels of platelet inhibition pre- and post-dose, with numerically slightly more variability with 60 mg: mean (SD) pre-dose PRU values were 59 ± 63 and 47 ± 43 for ticagrelor 60 and 90 mg, respectively (p = 0.34). High platelet reactivity, determined as PRU >208, was rare with the 60-mg pre-dose and was absent post-dose. Platelet reactivity pre- and post-dose, as measured by light transmittance aggregometry or vasodilator-stimulated phosphoprotein assays, was numerically but not significantly lower with 90 mg than with 60 mg. Aspirin response was not affected by either dose. Conclusions Ticagrelor 60 mg bid achieved high levels of peak and trough platelet inhibition in nearly all patients, similar to that with 90 mg bid, helping to explain the efficacy of the lower ticagrelor dose in PEGASUS-TIMI 54.
- Subjects :
- Blood Platelets
Ticagrelor
Adenosine
Time Factors
Platelet Aggregation
aspirin
Myocardial Infarction
030204 cardiovascular system & hematology
Pharmacology
Placebo
03 medical and health sciences
chemistry.chemical_compound
0302 clinical medicine
P2Y12
Pharmacokinetics
medicine
Humans
030212 general & internal medicine
Aspirin
Dose-Response Relationship, Drug
business.industry
Thromboxane B2
Treatment Outcome
chemistry
Anesthesia
Purinergic P2Y Receptor Antagonists
P2Y12 receptor
Cardiology and Cardiovascular Medicine
business
coronary artery disease
TIMI
Follow-Up Studies
Blood sampling
medicine.drug
Subjects
Details
- ISSN :
- 07351097
- Volume :
- 67
- Database :
- OpenAIRE
- Journal :
- Journal of the American College of Cardiology
- Accession number :
- edsair.doi.dedup.....0278bfabfcca9ccdc190855d18215e59