Subanalyse PLATO: Grotere effectiviteit ticagrelor dan clopidogrel in ACSNieuws - Sep. 29, 2010
Greater antiplatelet effect with ticagrelor than clopidogrel in ACS
A subanalysis of the PLATO study indicates that platelet inhibition is more pronounced among acute coronary syndrome (ACS) patients taking ticagrelor than among those taking clopidogrel.
This difference in efficacy is present "during maintenance therapy and in the first hours of treatment," say Robert Storey (University of Sheffield, UK) and colleagues. "These effects likely explain a substantial portion of the superior efficacy of ticagrelor compared with clopidogrel."
As reported in the Journal of the American College of Cardiology, Storey and team used light transmittance aggregometry (LTA), and vasodilator-stimulated phosphoprotein (VASP) phosphorylation and P2Y12 assays to assess the platelet reactivity levels of 69 patients on maintenance therapy with clopidogrel 75 mg once daily (n=32) or ticagrelor 90 mg twice daily (n=37).
Platelet reactivity levels before and 2-4 hours after maintenance dose, were measured after at least 28 days of treatment.
The effects of clopidogrel (300 to 600 mg) and ticagrelor (180 mg) loading doses (LD) were also determined among 24 clopidogrel-naive patients who took a clopidogrel LD of 300 mg (n=7) or 600 mg (n=5), or a ticagrelor LD of 180 mg (n=12).
Storey and colleagues found that during maintenance therapy, platelet reactivity was reduced to a greater extent by ticagrelor than clopidogrel, with a mean post-dose LTA of 28% and 44%, respectively (p<0.001). P2Y12 and VASP phosphorylation measurements were also lower among ticagrelor- than clopidogrel-treated patients (p<0.001).
LD analysis revealed a similar trend, with ticagrelor LD patients exhibiting greater platelet aggregation inhibition than clopidogrel LD patients (p<0.01).
Of note, the team found that patients taking maintenance clopidogrel and concomitant proton pump inhibitor (PPI, n=13) had higher platelet reactivity than those taking clopidogrel alone (n=19). However, no significant difference was found between patients taking ticagrelor with concomitant PPI (n=12) and those taking ticagrelor alone (n=25).
"The finding that there was no apparent effect of PPIs on the response to ticagrelor provides reassurance about the appropriateness of co-prescribing ticagrelor and PPIs," suggest the researchers.
They conclude: "This PLATO substudy is the largest assessment to date of platelet reactivity in the maintenance phase of treatment of ACS patients with ticagrelor and incorporated additional methods of assessing P2Y12 inhibition."