Compared with clopidogrel, ticagrelor achieves better antiplatelet effect in the first hours of treatment and in maintenance therapy for patients with acute coronary syndromes (ACS), according to the substudy PLATO PLATELET published online Sept. 9 in the Journal of the American College of Cardiology.
“Ticagrelor, an oral, reversibly binding platelet P2Y 12 receptor inhibitor, yields greater inhibition of platelet aggregation than clipidogrel,” the authors wrote.
Because the PLATO (PLATelet inhibition and patient Outcomes) study found that ticagrelor (AstraZeneca) decreased incidences of CV death, MI and stroke when compared to clopidogrel (Plavix, Bristol-Myers Squibb/Sanofi-Aventis), Robert F. Storey, MD, of the University of Sheffield in England, and colleagues conducted the PLATO PLATELET substudy to further understand and compare the two aforementioned drugs' effects on patients with ACS.
During the substudy, patients were broken down into two arms: those who received the study drug for at least 28 days and those who were not administered clopidogrel within the past 14 days and had not received ticagrelor. The researchers also collected venous blood samples from patients via venipuncture.
Sixty-nine patients were enrolled into the substudy—32 patients were administered a 28 day maintenance treatment with clopidogrel 75 mg/day and 37 patients received ticagrelor 90 mg twice daily.
Twenty-four “clopidogrel-naive” patients were enrolled to receive either a 300 mg (seven patients) or 600 mg loading dose (five patients) of clopidogrel and 12 patients received a 180 mg loading dose of ticagrelor.
Light transmittance aggregometry (LTA) responses were lower in the ticagrelor group compared to the clopidogrel group, and researchers found that P2Y 12 gene assay measurements were lower in those administered ticagrelor.
The researchers noted that ticagrelor achieved marked inhibition by one hour post-dose in all but one patient. The results also showed a greater effect of ticagrelor at four hours compared with clopidogrel with use of the VerifyNow (Accumetrics) assessment.
In response to the study therapy according to thresholds of ischemic risk, the researchers found almost no poor responders in the population administered ticagrelor during maintenance treatment; however being a poor responder on clopidogrel was fairly common.
Patients who were treated with maintenance therapy with both clopidogrel and proton pump inhibitor were shown to have greater platelet aggregation values compared to patients administered clopidogrel and not receiving a proton pump inhibitor.
“There was no difference in platelet reactivity between ticagrelor-treated patients receiving or not receiving this comedication,” the authors wrote.
“All the platelet function measurements show greater levels of inhibition with ticagrelor compared with clopidogrel, and the discrimination between the two treatment groups with the VerifyNow P2Y 12 system is striking,” the authors wrote.
Additionally, the authors said that acute coronary syndrome patients treated with ticagrelor had a more rapid onset of action than with clopidogrel.
The authors noted that potential limitations of the study could have stemmed from an insufficient number of clopidogrel-naive patients who received standard and double clopidogrel loading doses, as well as limitations from the number of patients in the maintenance phase.
“Ticagrelor demonstrates a greater platelet inhibitory effect than clopidogrel in acute coronary syndrome patients both during maintenance therapy and in the first hours of treatment,” the author concluded. “These effects likely explain a substantial portion of the superior efficacy of ticagrelor compared with clopidogrel.”