Dataset Information

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

ABSTRACT:

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.

SUBMITTER: Rosenson RS

PROVIDER: S-EPMC6556022 | biostudies-literature | 2019 Jun

REPOSITORIES: biostudies-literature

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Publications

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

Rosenson Robert S RS Chen Qinzhong Q Najera Sherwin D SD Krishnan Prakash P Lee Martin L ML Cho Daniel J DJ

Cardiovascular diabetology 20190607 1

<h4>Background</h4>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).< ...[more]

PMID: 31174526

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Project description:To determine the prevalence of poor response to aspirin (ASA) therapy over 12-month follow-up in patients with lower extremity peripheral arterial disease (PAD), and to compare the classification agreement among different ASA response assays.Patients with PAD on ASA therapy at baseline were included from the ongoing Effect of Lipid Modification on Peripheral Arterial Disease after Endovascular Intervention Trial (ELIMIT), which is a randomized trial testing whether combination treatment with ezetimibe, niacin, and a statin will halt/regress atherosclerosis compared with statin monotherapy. Patients who had baseline platelet testing and repeat testing at 6-month or 12-month follow-up were included. ASA responsiveness was tested using three different assays: Optical aggregation with 0.5 mg/mL of arachidonic acid (AA), optical aggregation with 10 ?M of adenosine diphosphate (ADP), and platelet function analyzer-100 (PFA-100) testing with collagen/epinephrine (Epi) loaded cartridges. ASA response was defined as AA aggregation <30%, ADP aggregation <70%, or PFA-100 Epi >164 seconds. Patients who showed response to ASA at baseline were classified as Responders. Poor response to ASA was defined as AA aggregation ? 30%, ADP aggregation ? 70%, or PFA-100 Epi ? 164 seconds. Patients who showed poor response (PR) to an assay at baseline, but then were responsive at follow-up visits were classified as Initial PRs. Patients who showed poor response at baseline and all follow-up visits were classified as Persistent PRs. The classification agreement between assays was tested using the kappa statistic.Of 102 patients randomized in ELIMIT, 80 patients satisfied inclusion criteria. There were no significant baseline demographic differences between Responders, Initial PRs, and Persistent PRs. The prevalence of persistent poor response varied by the assay used; 5% of subjects (4/80) were Persistent PRs by AA aggregation, compared with 27.5% (22/80) of subjects by ADP aggregation and 9.9% (7/71) of patients by PFA-100 Epi. Regarding the agreement of the assays, only AA aggregation and PFA-100 Epi agreed significantly (K = 0.3223; 95% confidence interval [CI] 0.15-0.493; P = .0001), and though statistically significant, the magnitude of this agreement is small. AA aggregation and ADP aggregation did not agree (K = 0.1161; 95% CI -0.004-0.236; P = .029), nor did ADP aggregation and PFA-100 Epi (K = 0.0044; 95% CI -0.151-0.160; P = .48).Between 5% and 27.5% of PAD patients were Persistent PRs to ASA over 6- to 12-month follow-up using different platelet assays. Further, these commonly used platelet assays show weak agreement in determining poor response to aspirin.

Dataset Information

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

Background

Methods

Results

Conclusions

Publications

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

Similar Datasets

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