Cargando…

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 i...

Descripción completa

Detalles Bibliográficos
Autores principales: Rosenson, Robert S., Chen, Qinzhong, Najera, Sherwin D., Krishnan, Prakash, Lee, Martin L., Cho, Daniel J.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6556022/
https://www.ncbi.nlm.nih.gov/pubmed/31174526
http://dx.doi.org/10.1186/s12933-019-0882-5
_version_ 1783425259752390656
author Rosenson, Robert S.
Chen, Qinzhong
Najera, Sherwin D.
Krishnan, Prakash
Lee, Martin L.
Cho, Daniel J.
author_facet Rosenson, Robert S.
Chen, Qinzhong
Najera, Sherwin D.
Krishnan, Prakash
Lee, Martin L.
Cho, Daniel J.
author_sort Rosenson, Robert S.
collection PubMed
description 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 ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12933-019-0882-5) contains supplementary material, which is available to authorized users.
format Online
Article
Text
id pubmed-6556022
institution National Center for Biotechnology Information
language English
publishDate 2019
publisher BioMed Central
record_format MEDLINE/PubMed
spelling pubmed-65560222019-06-13 Ticagrelor improves blood viscosity-dependent microcirculatory flow in patients with lower extremity arterial disease: the Hema-kinesis clinical trial Rosenson, Robert S. Chen, Qinzhong Najera, Sherwin D. Krishnan, Prakash Lee, Martin L. Cho, Daniel J. Cardiovasc Diabetol Original Investigation 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 ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12933-019-0882-5) contains supplementary material, which is available to authorized users. BioMed Central 2019-06-07 /pmc/articles/PMC6556022/ /pubmed/31174526 http://dx.doi.org/10.1186/s12933-019-0882-5 Text en © The Author(s) 2019 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Original Investigation
Rosenson, Robert S.
Chen, Qinzhong
Najera, Sherwin D.
Krishnan, Prakash
Lee, Martin L.
Cho, Daniel J.
Ticagrelor improves blood viscosity-dependent microcirculatory flow in patients with lower extremity arterial disease: the Hema-kinesis clinical trial
title Ticagrelor improves blood viscosity-dependent microcirculatory flow in patients with lower extremity arterial disease: the Hema-kinesis clinical trial
title_full Ticagrelor improves blood viscosity-dependent microcirculatory flow in patients with lower extremity arterial disease: the Hema-kinesis clinical trial
title_fullStr Ticagrelor improves blood viscosity-dependent microcirculatory flow in patients with lower extremity arterial disease: the Hema-kinesis clinical trial
title_full_unstemmed Ticagrelor improves blood viscosity-dependent microcirculatory flow in patients with lower extremity arterial disease: the Hema-kinesis clinical trial
title_short Ticagrelor improves blood viscosity-dependent microcirculatory flow in patients with lower extremity arterial disease: the Hema-kinesis clinical trial
title_sort ticagrelor improves blood viscosity-dependent microcirculatory flow in patients with lower extremity arterial disease: the hema-kinesis clinical trial
topic Original Investigation
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6556022/
https://www.ncbi.nlm.nih.gov/pubmed/31174526
http://dx.doi.org/10.1186/s12933-019-0882-5
work_keys_str_mv AT rosensonroberts ticagrelorimprovesbloodviscositydependentmicrocirculatoryflowinpatientswithlowerextremityarterialdiseasethehemakinesisclinicaltrial
AT chenqinzhong ticagrelorimprovesbloodviscositydependentmicrocirculatoryflowinpatientswithlowerextremityarterialdiseasethehemakinesisclinicaltrial
AT najerasherwind ticagrelorimprovesbloodviscositydependentmicrocirculatoryflowinpatientswithlowerextremityarterialdiseasethehemakinesisclinicaltrial
AT krishnanprakash ticagrelorimprovesbloodviscositydependentmicrocirculatoryflowinpatientswithlowerextremityarterialdiseasethehemakinesisclinicaltrial
AT leemartinl ticagrelorimprovesbloodviscositydependentmicrocirculatoryflowinpatientswithlowerextremityarterialdiseasethehemakinesisclinicaltrial
AT chodanielj ticagrelorimprovesbloodviscositydependentmicrocirculatoryflowinpatientswithlowerextremityarterialdiseasethehemakinesisclinicaltrial