August 21, 2015
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Ticagrelor yields greater platelet inhibition vs. clopidogrel in black patients with CAD

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Among black patients with stable CAD being treated with low-dose aspirin, ticagrelor yields more effective platelet inhibition vs. clopidogrel, according to recent findings.

In a multicenter, open-label, crossover pilot study, researchers evaluated 34 black adult patients with documented stable CAD who were taking aspirin at doses of 75 mg to 100 mg per day. The cohort had a mean age of 62.3 years and 67.6% were men.

Patients were randomly assigned at a 1:1 ratio to receive one of two treatment regimens:

  • A 600 mg clopidogrel loading dose followed by a maintenance dose of 75 mg once daily for 7-9 days, then switching to a 180 mg ticagrelor (Brilinta, AstraZeneca) loading dose followed by a 90-mg twice-daily maintenance dose for 7-9 days; or
  • The same regimens in reverse order, beginning with ticagrelor and switching to clopidogrel.

A 10- to 14-day washout period separated each phase of the treatment. Patients maintained a self-administered aspirin regimen over the course of the study.

Study visits occurred on days 1, 7 and 8 of each treatment interval. Platelet function testing was conducted through blood samples taken before the initial dose of medication and at 0.5, 2 and 8 hours after the loading dose on day 1; before dosing and at 2 and 8 hours following treatment on day 7; and at the conclusion of the dosing period on day 8.

The primary endpoint was platelet reactivity 2 hours after the day 1 loading dose for ticagrelor and clopidogrel. Secondary endpoints included platelet reactivity at other time points on days 1, 7 and 8 of each treatment.

Treatment with ticagrelor yielded lower least-squares platelet reactivity units (PRU) than clopidogrel (27.6 vs. 211.2) at 2 hours after the loading dose. The researchers observed a statistically significant least-squares mean difference in PRU between treatments (ticagrelor minus clopidogrel, –183.6; 95% CI, –213.9 to –153.3). Based on analysis of individual patient PRU profiles, ticagrelor achieved a more pronounced and sustained effect on PRU at 2 hours following the loading dose compared with clopidogrel.

Ticagrelor resulted n a greater percent reduction in PRU from baseline at all time points, with a 65.9% (95% CI, 56.5-75.3) least-squares mean difference in percent reduction of PRU between ticagrelor (90% reduction) and clopidogrel (24.1% reduction) 2 hours after loading dose. The rate of high on-treatment platelet reactivity (≥ 208) was lower with ticagrelor vs. clopidogrel at 0.5 hours (34.5% of patients vs. 92.9%; P < .00001) and 2 hours post-loading dose (0% vs. 57.1%; P < .000001).

“Ticagrelor provided greater platelet inhibition than clopidogrel in this pilot study,” the researchers wrote. “Furthermore, the pharmacokinetic profile of ticagrelor observed in this study was consistent with that reported in previous studies.” – by Jennifer Byrne

Disclosure: AstraZeneca funded the study. Waksman reports receiving consulting fees or honorarium and/or institutional payments for investigator grants from Abbott Vascular, AstraZeneca, Biosensors, Biotronik, Boston Scientific, Edwards Lifesciences, InfraReDx and Medtronic Vascular. Please see the full study for a list of all other researchers’ relevant financial disclosures.