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

Rosenson, Robert S.; Chen, Qinzhong; Najera, Sherwin D.; Lee, Martin L.; Cho, Daniel J.

doi:10.1007/s10557-018-6815-9

Cited by 13 publications

(24 citation statements)

References 32 publications

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“…Details of the trial design have been reported previously. Hema-kinesis is a 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 ) blood viscosity ( NCT02325466 ) [22]. The inclusion and exclusion criteria are provided in Table 1.…”

Section: Methodsmentioning

confidence: 99%

“…Ticagrelor and matching placebo, as well as aspirin and matching placebo, were compounded then over-encapsulated to maintain double-blind conditions. Stability and antimicrobial quality assurance tests were performed prior to and post over-encapsulation [22]. The Clinical Materials Services Unit of the University of Rochester Medical Center (Rochester, NY) prepared study medication kits.…”

Section: Methodsmentioning

confidence: 99%

“…Laser Doppler flowmetry, TBI and ABI are measured using the PeriFlux 5000 (Stockholm, Sweden) as previously described [22, 25]. Both feet were examined except in the setting of unilateral amputation.…”

Section: Methodsmentioning

confidence: 99%

“…Study participants had measurements of the complete blood count, electrolytes and liver function tests. At the time of each study encounter, potential adverse events of special interest, including bleeding complications, were reviewed [22].…”

Section: Methodsmentioning

confidence: 99%

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

Rosenson

Chen

Najera

et al. 2019

Cardiovasc Diabetol

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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.

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

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

Rosenson

Chen

Najera

et al. 2019

Cardiovasc Diabetol

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“…Our previous study revealed that in patients with acute ischemic stroke treated with clopidogrel, a good CYP2C19 genotype for clopidogrel metabolism was associated with a 31% decrease in the relative risk of recurrent stroke [10]. Informative studies on pharmacological therapies for reducing BV are limited [11,12]. One study showed that in patients with subclinical carotid or femoral atherosclerosis, clopidogrel reduces the mean low-shear BV by 18% after 3 weeks of treatment [12].…”

Section: Introductionmentioning

confidence: 99%

The good genotype for clopidogrel metabolism is associated with decreased blood viscosity in clopidogrel-treated ischemic stroke patients

Hyun

Won

2020

J Neurocrit Care

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Background: Blood viscosity (BV) is a measurement of the intrinsic resistance of blood to flow, and high BV increases thromboembolic risk. Although laboratory documentation of clopidogrel resistance has been shown to predict an increased risk of cardiovascular events in patients with ischemic stroke, there is no evidence that cytochrome P450 2C19 (CYP2C19) polymorphisms in clopidogrel-treated patients influence BV after ischemic stroke. Methods: Patients with ischemic stroke or transient ischemic attack within 7 days of symptom onset from April 2018 to October 2019 were included. Patients were classified into the good genotype group for clopidogrel metabolism (ultrarapid or extensive metabolizer) and poor genotype group (intermediate/unknown or poor metabolizer) based on their CYP2C19 genotype status. A scanning capillary-tube viscometer was used to assess whole BV, and patients were divided into decreased BV and increased BV groups. Results: The final analyses included 174 patients (109 men and 65 women) with a mean age of 66.4±11.2 years. The good genotype was found in 44% of patients with decreased systolic BV (SBV) and 27% of those with increased SBV (P=0.029), suggesting that BV changes were related to the CYP2C19 genotype for clopidogrel metabolism. Binary logistic regression analysis showed that CYP2C19 genotype status (P=0.024) and baseline SBV (P<0.001) were significantly associated with decreased BV. The good genotype for clopidogrel metabolism was associated with decreased BV in patients with ischemic stroke treated with clopidogrel. Conclusion:The present results indicate that the effect of clopidogrel treatment on ischemic stroke prevention could be modulated not only by inhibition of platelet function but also by changes in the hemorheological profile.

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Diabetes mellitus and muscle infarction

Subauste

2020

Diabetes Mellitus

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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

Cited by 13 publications

References 32 publications

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

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

The good genotype for clopidogrel metabolism is associated with decreased blood viscosity in clopidogrel-treated ischemic stroke patients

Diabetes mellitus and muscle infarction

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