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

BACKGROUND: 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). METHODS: 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. RESULTS: 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). CONCLUSIONS: Ticagrelor should be considered in the treatment of microvascular disease in patients with LEAD and T2DM. Trial registration Registration number: NCT02325466, registration date: December 25, 2014.

Ticagrelor and the Prevention of Microvascular Complications in Diabetes Patients with Lower Extremity Arterial Disease; Rationale and Design of the Hema-Kinesis Trial.

BACKGROUND: Lower extremity arterial disease (LEAD) occurs more common in patients with diabetes than without diabetes. Microvascular complications of diabetes contribute to higher rates of adverse limb events in patients with LEAD. Blood flow in the macrocirculation and microcirculation is reduced with increasing low-shear and high-shear blood viscosity. We hypothesize that the adenosine enhancing properties of ticagrelor will reduce low-shear blood viscosity and improve microcirculatory flow in the dorsum of the feet of patients with type 2 diabetes. Ticagrelor is a P2Y12 receptor antagonist with evidence of cardiovascular event reduction in patients with acute coronary syndromes and those with a previous myocardial infarction. In a large multicenter trial of patients with symptomatic LEAD and a history of limb revascularization, ticagrelor was no more effective than clopidogrel in reducing cardiovascular disease events; however, this trial was not designed to investigate microvascular complications of diabetes. DESIGN: Hema-kinesis will evaluate whether ticagrelor monotherapy or ticagrelor combined with aspirin as compared with aspirin monotherapy can reduce blood viscosity-dependent blood flow in the feet of type 2 diabetes patients with LEAD. Eligible study participants will be randomized into a three-arm double-dummy crossover trial design. All subjects will have baseline blood viscosity measurements and determinations of microvascular flow using laser Doppler flowmetry. If the results of Hema-kinesis are positive, ticagrelor should be considered as treatment to reduce microvascular complications of LEAD in patients with type 2 diabetes.

Heterozygous familial hypercholesterolemia presenting as chylomicronemia syndrome.

Heterozygous familial hypercholesterolemia (HeFH) is characterized by a twofold elevation in low-density lipoprotein cholesterol. Severe elevations in triglycerides are an uncommon manifestation. In this case report, we discuss an atypical presentation of the chylomicronemia syndrome in a patient with HeFH. Genetic analyses of the low-density lipoprotein receptor mutation and single nucleotide polymorphisms that elevate triglycerides provide confirmation for this atypical presentation of HeFH.