Author + information
- Joshua Perese,
- Jared Cline,
- David Shavelle,
- Vincent Rowe,
- Jorge Caro and
- Leonardo C. Clavijo
Critical limb ischemia (CLI) is associated with increased risk of amputations, cardiovascular events and mortality. Antiplatelet therapy is a crucial component of CLI treatment. High on-treatment platelet reactivity (HPR), defined by a platelet reactivity unit (PRU) score above 208 on the VerifyNow P2Y12 Assay, is associated with increased risk of ischemic events. Low on-treatment platelet reactivity (LPR), defined by a PRU score below 85, is associated with increased risk of bleeding events. The goal of the current study is to investigate a therapeutic range (TR) of clopidogrel and ticagrelor defined by PRU scores between 85 and 208.
In a retrospective analysis, data from the “Switch To Ticagrelor in Critical Limb Ischemia Anti-Platelet Study ‘STT-CLIPS’” study was used to assess the therapeutic window of 48 CLI patients. Data included four measurements of platelet reactivity using the VerifyNow P2Y12 Assay: baseline (before daily dose) and steady state (6 hours after daily dose) while taking clopidogrel 75 mg daily for at least two weeks, and two weeks after switching to ticagrelor 90 mg twice daily.
At baseline, 47.9% of patients on clopidogel were within TR (37.5% HPR, 14.6% LPR) compared to 10.2% on ticagrelor (2.1% HPR, 87.5% LPR; p< 0.001). At steady state, 43.8% of patients on clopidogel were within TR (31.3% HPR, 25.0% LPR) compared to 10.2% on ticagrelor (2.1% HPR, 87.5% LPR; p< 0.01). HPR was more common on clopidogrel compared to ticagrelor at baseline (37.5% vs. 2.1%; p< 0.0001) and at steady state (31.3% vs. 2.1%; p< 0.001). LPR was more common in ticagrelor compared to clopidogrel at baseline (87.5% vs. 14.6%, p< 0.0001) and at steady state (87.5% vs. 25%, p< 0.0001).
With only 42.9% of patients on clopidogrel (at steady state) being in the therapeutic range of platelet inhibition, there is a reasonable concern for either bleeding or ischemic complications. Though ticagrelor has been proposed as an antiplatelet alternative in patients with CLI, this study observes an excess of platelet inhibition, warranting concern for bleeding complications.