Switch to Ticagrelor in critical limb ischemia antiplatelet study (STT-CLIPS)

To investigate platelet reactivity in patients with critical limb ischemia (CLI) after switching from clopidogrel to ticagrelor.

High on-treatment platelet reactivity (HPR) is highly prevalent in patients with CLI treated with clopidogrel. The effect of ticagrelor in patients with CLI is not known, however.

We performed P2Y12 platelet receptor inhibition studies (VASP and VerifyNow) in 50 patients with CLI. Tests were performed before and 6±1h after daily 75mg clopidogrel dose. Patients were then switched to ticagrelor 90mg twice daily for two weeks and platelet assays repeated. Patients were divided based on VerifyNow P2Y12 reaction units (PRU). Group 1: HPR defined as PRU ≥208 and Group 2: Appropriate platelet inhibition (API), PRU <208.

After two weeks of uninterrupted antiplatelet therapy, mean PRU results were 173 PRU and 71 PRU at baseline (p<0.0001) and 140 PRU and 63 PRU after 6h (p<0.0001) for clopidogrel and ticagrelor, respectively. Before daily clopidogrel dose, 36% of patients (n=18) demonstrated HPR and after 6h, 30% (n=15). One patient (2%) had HPR on ticagrelor. Ninety-four percent of patients with HPR on clopidogrel demonstrated appropriate platelet inhibition after switching to ticagrelor and all patients with API on clopidogrel remained with API after switching to ticagrelor. Six hours after daily dosing, VASP-PRI >50% was found in 42% of clopidogrel and 2% of ticagrelor treated patients.

Among patients with CLI, ticagrelor achieved greater platelet inhibition than clopidogrel during maintenance treatment and at 6h after daily dosing. High on-treatment platelet reactivity to clopidogrel in patients with CLI can be overcome by switching to ticagrelor.