Inhibitory effects of ticagrelor compared with clopidogrel on platelet function in patients with acute coronary syndromes: the PLATO (PLATelet inhibition and patient Outcomes) PLATELET substudy.
OBJECTIVE
The PLATO (PLATelet inhibition and patient Outcomes) PLATELET substudy aimed to compare the antiplatelet effects of clopidogrel and ticagrelor in patients with acute coronary syndromes.


BACKGROUND
The PLATO study demonstrated superiority of ticagrelor over clopidogrel in the prevention of ischemic events in patients with acute coronary syndromes.


METHODS
Patients were randomized to receive either clopidogrel (300- to 600-mg loading dose [LD], 75 mg/day) or ticagrelor (180-mg LD, 90 mg twice daily). The effects of maintenance therapy were studied in 69 patients pre- and 2 to 4 h post-dose after at least 28 days. The LD effect was studied in 24 clopidogrel-naive patients. Light transmittance aggregometry (adenosine diphosphate 5 to 20 μM), VerifyNow P2Y12, and VASP phosphorylation assays were performed.


RESULTS
During maintenance therapy, ticagrelor achieved greater suppression of platelet reactivity compared with clopidogrel. The mean maximum light transmittance aggregometry responses (adenosine diphosphate 20 μM) post-maintenance dose were 44±15% for clopidogrel and 28±10% for ticagrelor (p<0.001). High platelet reactivity was seen more frequently in the clopidogrel group. Proton pump inhibitor use was associated with higher platelet reactivity with clopidogrel but not ticagrelor. The ticagrelor LD also achieved greater inhibition of platelet aggregation compared with the clopidogrel LD.


CONCLUSIONS
Ticagrelor achieves greater antiplatelet effect than clopidogrel in patients with acute coronary syndromes, both in the first hours of treatment and during maintenance therapy.
Storey
Robert F
RF
Department of Cardiovascular Science, University of Sheffield, and NIHR Cardiovascular Biomedical Research Unit, Sheffield, United Kingdom. r.f.storey@sheffield.ac.uk
Angiolillo
Dominick J
DJ
Patil
Shankar B
SB
Desai
Bhaloo
B
Ecob
Rosemary
R
Husted
Steen
S
Emanuelsson
Hakan
H
Cannon
Christopher P
CP
Becker
Richard C
RC
Wallentin
Lars
L
D054058:Acute Coronary Syndrome / Q000188:drug therapy* / Q000503:physiopathology; D000241:Adenosine / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D000368:Aged; D001792:Blood Platelets / Q000187:drug effects* / Q000502:physiology*; D000077144:Clopidogrel; D015331:Cohort Studies; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D000077486:Ticagrelor; D013988:Ticlopidine / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D016896:Treatment Outcome
D010975:Platelet Aggregation Inhibitors; D000077144:Clopidogrel; D000077486:Ticagrelor; D000241:Adenosine; D013988:Ticlopidine