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

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Abstract

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.

Summary

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.

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Funding

This study was funded by Astra Zeneca (grant number ISSBRIL0174).

Author information

Authors and Affiliations

  1. Cardiometabolics Unit, Zena and Michael A. Wiener Cardiovascular Institute, Marie-Josee and Henry R. Kravis Center for Cardiovascular Health, One Gustav L. Levy Place, Hospital Box 1030, New York, NY, 10029, USA

    Robert S. Rosenson, Qinzhong Chen & Sherwin D. Najera

  2. Mount Sinai Hospital, Icahn School of Medicine at Mount Sinai, New York, NY, USA

    Robert S. Rosenson, Qinzhong Chen & Sherwin D. Najera

  3. UCLA Fielding School of Public Health, Los Angeles, CA, USA

    Martin L. Lee

  4. Rheovector LLC, King of Prussia, PA, USA

    Daniel J. Cho

Authors
  1. Robert S. Rosenson
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  2. Qinzhong Chen
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  3. Sherwin D. Najera
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  4. Martin L. Lee
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  5. Daniel J. Cho
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Corresponding author

Correspondence to Robert S. Rosenson.

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Conflict of Interest

Dr. Rosenson reports having received research support from Akcea, Amgen, Medicines Company, and Regeneron. He has participated in Advisory Boards for Akcea, CVS Caremark, Regeneron, and received honoraria from Akcea, Amgen, Kowa, Pfizer, and Sanofi. In 2014, he attended an Advisory Board meeting for Astra Zeneca. Dr. Chen has no conflict of interest. Mr. Najera has no conflict of interest. Dr. Lee reports consulting fees from Rheovector, and Mr. Cho reports consulting fees from Rheovector.

Ethical Approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. This trial was approved by the Institutional Review Board at the Icahn School of Medicine at Mount Sinai, New York, NY. Informed consent was obtained from all individual participants included in the study.

Disclosures

Hema-kinesis is an investigator-initiated trial that was initiated and designed by investigators at the Cardiometabolics Unit at the Icahn School of Medicine. This trial was funded by an unrestricted grant from Astra Zeneca. The sponsor had no involvement in the study design, conduct, interpretation of results, or preparation of this manuscript. Dr. Rosenson has received research funding from Astra Zeneca and participated in an advisory board sponsored by Astra Zeneca in 2014. Dr. Chen and Mr. Najera have no disclosures. Dr. Lee has received consulting fees from Rheovector. Mr. Cho has received consulting fees from Rheovector.

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Rosenson, R.S., Chen, Q., Najera, S.D. et al. Ticagrelor and the Prevention of Microvascular Complications in Diabetes Patients with Lower Extremity Arterial Disease; Rationale and Design of the Hema-Kinesis Trial. Cardiovasc Drugs Ther 32, 443–451 (2018). https://doi.org/10.1007/s10557-018-6815-9

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  • DOI: https://doi.org/10.1007/s10557-018-6815-9

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