Ticagrelor improves blood viscosity-dependent microcirculatory flow in patients with lower extremity arterial disease: the Hema-kinesis clinical trial

摘要

Microvascular blood flow (MBF) impairment in patients with lower extremity arterial disease (LEAD) is associated with more severe major adverse limb events (MALE). The contribution of ticagrelor, a P2Y12 antagonist and an adenosine enhancer, on blood viscosity (BV) and BV-dependent MBF in LEAD is unknown. The aim of the trial is to investigate the effects of ticagrelor on BV, and explore the association of BV-dependent MBF in participants with LEAD and type 2 diabetes (T2DM). Randomized, double-blind, double-dummy, crossover trial design that compares treatment with aspirin 81?mg/ticagrelor placebo, aspirin 81?mg/ticagrelor 90?mg twice daily and aspirin placebo/ticagrelor 90?mg twice daily on high-shear (300?s?1) and low-shear (5?s?1) BV, and laser Doppler flowmetry (LDF) in the dorsum of the feet of participants with T2DM. We randomized 70 (45% female) participants aged (mean?±?SD) 72?±?9?years. The duration of LEAD was 12.3?±?10.3?years, and 96.9% reported intermittent claudication symptoms. Use of statins was 93% (high-intensity 43%, moderate intensity 49%), renin–angiotensin–aldosterone system inhibitors (75%) and beta-blockers (61%). Treatment with ticagrelor with or without aspirin reduced high-shear BV by 5%, in both cases, while aspirin monotherapy increased high-shear BV by 3.4% (p??0.0001). Ticagrelor with or without aspirin reduced low-shear BV by 14.2% and 13.9% respectively, while aspirin monotherapy increased low-shear BV by 9.3% (p??0.0001). The combination of ticagrelor and aspirin increased MBF in the left foot compared to the other two treatments (p?=?0.02), but not in the right foot (p?=?0.25). Ticagrelor should be considered in the treatment of microvascular disease in patients with LEAD and T2DM.