Antiplatelet effect of aspirin during 24 h in patients with type 2 diabetes without cardiovascular disease

Vernstrøm, Liv; Funck, Kristian Løkke; Grove, Erik Lerkevang; Laugesen, Esben; Baier, Jonathan Mathias; Hvas, Anne‐Mette; Poulsen, Per Løgstrup

doi:10.1016/j.thromres.2017.11.013

Cited by 12 publications

(14 citation statements)

References 39 publications

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“…For example, whilst some evidence suggests that aspirin therapy targeted by assessment of cardiovascular and bleeding risk may be of benefit [40], guidelines remain conflicted on the extent to which, if at all, aspirin therapy should be recommended in this situation [41,42]. P2Y 12 inhibitors are alternative antiplatelet agents to aspirin with the potential benefits of prolonged presence in the plasma that might overcome reduced aspirin effect due to high platelet turnover and avoiding gastric erosion [43]. Three orally-active drugs, clopidogrel, prasugrel and ticagrelor are commonly-available [6].…”

Section: Discussionmentioning

confidence: 99%

Aspirin, clopidogrel and prasugrel monotherapy in patients with type 2 diabetes mellitus: a double-blind randomised controlled trial of the effects on thrombotic markers and microRNA levels

Parker

Schulte

Barwari

et al. 2020

Cardiovasc Diabetol

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Background: Despite increased atherothrombotic risk in type 2 diabetes mellitus, (T2DM) the best preventative antithrombotic strategy remains undetermined. We defined the effects of three antiplatelet agents on functional readout and biomarker kinetics in platelet activation and coagulation in patients with T2DM. Materials and methods: 56 patients with T2DM were randomised to antiplatelet monotherapy with aspirin 75 mg once daily (OD), clopidogrel 75 mg OD or prasugrel 10 mg OD during three periods of a crossover study. Platelet aggregation (PA) was determined by light-transmittance aggregometry and P-selectin expression by flow cytometry. Markers of fibrin clot dynamics, inflammation and coagulation were measured. Plasma levels of 14 miRNA were assessed by quantitative polymerase chain reactions. Results: Of the 56 patients, 24 (43%) were receiving aspirin for primary prevention of ischaemic events and 32 (57%) for secondary prevention. Prasugrel was the strongest inhibitor of ADP-induced PA (mean ± SD maximum response to 20μmol/L ADP 77.6 ± 8.4% [aspirin] vs. 57.7 ± 17.6% [clopidogrel] vs. 34.1 ± 14.1% [prasugrel], p < 0.001), P-selectin expression (30 μmol/L ADP; 45.1 ± 21.4% vs. 27.1 ± 19.0% vs. 14.1 ± 14.9%, p < 0.001) and collagen-induced PA (2 μg/ mL; 62.1 ± 19.4% vs. 72.3 ± 18.2% vs. 60.2 ± 18.5%, p < 0.001). Fibrin clot dynamics and levels of coagulation and inflammatory proteins were similar. Lower levels of miR-24 (p = 0.004), miR-191 (p = 0.019), miR-197 (p = 0.009) and miR-223 (p = 0.014) were demonstrated during prasugrel-therapy vs. aspirin. Circulating miR-197 was lower in those cardiovascular disease during therapy with aspirin (p = 0.039) or prasugrel (p = 0.0083). Conclusions: Prasugrel monotherapy in T2DM provided potent platelet inhibition and reduced levels of a number of platelet-associated miRNAs. miR-197 is a potential marker of cardiovascular disease in this population. Clinical outcome studies investigating prasugrel monotherapy are warranted in individuals with T2DM.

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Section: Discussionmentioning

confidence: 99%

Aspirin, clopidogrel and prasugrel monotherapy in patients with type 2 diabetes mellitus: a double-blind randomised controlled trial of the effects on thrombotic markers and microRNA levels

Parker

Schulte

Barwari

et al. 2020

Cardiovasc Diabetol

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“…The incidence of diabetes mellitus (DM), a common chronic disease in clinical practice that affected over 100 million people in China, is increasing each year (1). It has been reported that DM is a persistent metabolic disorder, which can be induced by hypoglycemia and impaired glucose tolerance due to insulin deficiency and resistance (2,3). Type 1 DM is caused by the reduction of insulin due to the destruction of islet cells and accounts for a minority of patients with DM (4,5).…”

Section: Introductionmentioning

confidence: 99%

Reduced expression of microRNA‑199a‑3p is associated with vascular endothelial cell injury induced by type 2 diabetes mellitus

Wang

Tang

2018

Exp Ther Med

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The aim of the present study was to investigate the function and mechanism of action of microRNA (miRNA or miR)-199a-3p in vascular endothelial cell injury induced by type 2 diabetes mellitus (T2DM). A total of 36 patients with T2DM (26 males and 10 females; mean age, 52.5±7.0 years) and 20 healthy subjects (10 males and 10 females; mean age, 55.6±4.5 years) were included in the present study. Peripheral blood samples were obtained from all participants and total RNA was extracted Reverse transcription-quantitative polymerase chain reaction was performed to determine the expression of miR-199a-3p. Following the transfection of human umbilical vein endothelial cells (HUVECs) with a negative control (NC) miRNA or miR-199a-3p mimics, cell proliferation was assessed using a Cell Counting kit-8 assay. Cell migration was investigated using Transwell assays and flow cytometry was performed to detect the apoptosis of HUVECs. HUVECs were infected with Ad-GFP-LC3B and laser-scanning confocal microscopy was performed to observe autophagosomes in HUVECs. Western blotting was used to measure the expression of proteins associated with autophagy and the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT)/nuclear factor (NF)-κB signaling pathway. MiR-199a-3p was downregulated in peripheral blood from patients with T2DM compared with healthy subjects. Transfection with miR-199a-3p mimics promoted the proliferation and migration of HUVECs. However, miR-199a-3p overexpression inhibited the apoptosis of HUVECs. MiR-199a-3p facilitated HUVEC autophagy by affecting autophagy-associated signaling pathways. Furthermore, miR-199a-3p regulated the biological functions of HUVECs via the PI3K/AKT/NF-κB signaling pathway. The results of the present study suggest that miR-199a-3p expression was reduced in patients with T2DM compared with healthy subjects and may be associated with vascular endothelial cell injury. In addition, miR-199a-3p promoted the proliferation, migration and autophagy of HUVECs, potentially by regulating the PI3K/AKT/NF-κB signaling pathway. Therefore, miR-199a-3p may function as protector of vascular endothelia.

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“…Our results might also indicate that people with diabetes may benefit from an alternate dosing regimen, perhaps twice‐daily dosing, which has been suggested previously . Our previous results on platelet function also support this hypothesis . Future studies should confirm the effectiveness and safety of this strategy.…”

Section: Discussionmentioning

confidence: 99%

“…In accordance with our matched design, paired t-test and the McNemar tests were used to test for differences in baseline characteristics. The sample size calculation was based on change in platelet aggregation and has been presented previously [12]. lnRHI and PWV were evaluated using a mixed model analysis.…”

Section: Discussionmentioning

confidence: 99%

Differential vascular effects of aspirin in people with Type 2 diabetes without cardiovascular disease and matched controls without diabetes

Vernstrøm¹,

Laugesen²,

Grove

et al. 2019

Diabet. Med.

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Aim We investigated whether the effect of low‐dose aspirin on endothelium‐dependent vasodilation and arterial stiffness in people with Type 2 diabetes is different from a matched control group. We examined acute and chronic effects, and effects over the 24h dosing interval. Methods In an open‐label parallel group intervention study, we included 21 participants with Type 2 diabetes and 21 age‐ and sex‐matched controls. Endothelium‐dependent vasodilation was assessed as the reactive hyperaemia index (lnRHI) measured by peripheral arterial tonometry (EndoPAT®). Arterial stiffness was assessed as pulse wave velocity (PWV) measured by applanation tonometry (SphygmoCor®). Measurements were performed prior to aspirin intake and 1h after aspirin administration (75 mg). Participants were then treated for 6 days, and measurements were repeated at 24 h and 1 h after aspirin intake. Results Baseline lnRHI did not differ between groups. The controls had an immediate increase in lnRHI after the first aspirin tablet. This was not observed in participants with diabetes (difference between groups; P < 0.05). After 1 week, both groups demonstrated increased lnRHI compared with baseline (P < 0.01). In participants with diabetes, lnRHI was significantly lower 24 h after aspirin administration compared with 1 h after administration (P < 0.05). This difference was not observed in controls (P = 0.84, difference between groups; P = 0.12). The effect on PWV did not differ between groups. Conclusion Aspirin had a reduced immediate effect on endothelium‐dependent vasodilation in participants with diabetes. Both groups had improved endothelial function after 1 week of treatment. Further, the effect of aspirin on endothelial function may be declining during a 24 h dosing interval in people with Type 2 diabetes. (Clinical Trial Registry No: 2016‐000515‐32)

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Antiplatelet effect of aspirin during 24 h in patients with type 2 diabetes without cardiovascular disease

Cited by 12 publications

References 39 publications

Aspirin, clopidogrel and prasugrel monotherapy in patients with type 2 diabetes mellitus: a double-blind randomised controlled trial of the effects on thrombotic markers and microRNA levels

Aspirin, clopidogrel and prasugrel monotherapy in patients with type 2 diabetes mellitus: a double-blind randomised controlled trial of the effects on thrombotic markers and microRNA levels

Reduced expression of microRNA‑199a‑3p is associated with vascular endothelial cell injury induced by type 2 diabetes mellitus

Differential vascular effects of aspirin in people with Type 2 diabetes without cardiovascular disease and matched controls without diabetes

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