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Multi-Omics Signatures Link to Ticagrelor Effects on Vascular Function in Patients With Acute Coronary Syndrome
Chor-Cheung Frankie Tam1, Yap-Hang Chan1, Yuen-Kwun Wong1
1Division of Cardiology, Queen Mary Hospital, The University of Hong Kong, China (C.-C.F.T., Y.-H.C., Y.-K.W., H.-F.T.).
Insights
Ticagrelor monotherapy significantly improved vascular endothelial function in patients with prior acute coronary syndrome compared to aspirin. This study highlights ticagrelor
Area of Science:
- Cardiovascular Medicine
- Pharmacology
- Vascular Biology
Background:
- Long-term antiplatelet therapy is crucial for patients with a history of acute coronary syndrome (ACS).
- Ticagrelor, a potent P2Y12 antagonist, is a key therapeutic option in this patient population.
- The comparative effects of ticagrelor and aspirin monotherapy on endothelial function remain an area of investigation.
Purpose of the Study:
- To compare the efficacy of ticagrelor versus aspirin monotherapy in improving vascular endothelial function.
- To assess the impact of ticagrelor on endothelial function markers in patients with prior ACS.
- To explore multi-omics changes associated with ticagrelor treatment.
Main Methods:
- A prospective, single-center, randomized controlled trial involving 200 patients with prior ACS.
- Patients were randomized to receive ticagrelor 60 mg twice daily or aspirin 100 mg once daily for 12 weeks.
- Primary endpoint: change in brachial artery flow-mediated dilation; Secondary endpoints: platelet activation, endothelial progenitor cells, plasma biomarkers, and multi-omics profiling.
Main Results:
- Ticagrelor significantly increased brachial artery flow-mediated dilation compared to aspirin (4.73% difference, P<0.001).
- No significant differences were observed in platelet activation markers, endothelial progenitor cell counts, or plasma levels of adenosine, IL-6, and EGF.
- Multi-omics analysis revealed associations between improved flow-mediated dilation and altered metabolism of amino acids and phospholipids with ticagrelor.
Conclusions:
- Ticagrelor 60 mg monotherapy significantly enhances brachial artery flow-mediated dilation in patients with prior ACS compared to aspirin.
- The vascular benefits of ticagrelor are linked to significant changes in metabolomic and lipidomic profiles.
- Further research may elucidate the precise mechanisms underlying ticagrelor's endothelial benefits.
Background:
Long-term antiplatelet agents including the potent P2Y12 antagonist ticagrelor are indicated in patients with a previous history of acute coronary syndrome. We sought to compare the effect of ticagrelor with that of aspirin monotherapy on vascular endothelial function in patients with prior acute coronary syndrome.
Methods:
This was a prospective, single center, parallel group, investigator-blinded randomized controlled trial. We randomized 200 patients on long-term aspirin monotherapy with prior acute coronary syndrome in a 1:1 fashion to receive ticagrelor 60 mg BD (n=100) or aspirin 100 mg OD (n=100). The primary end point was change from baseline in brachial artery flow-mediated dilation at 12 weeks. Secondary end points were changes to platelet activation marker (CD41_62p) and endothelial progenitor cell (CD34/133) count measured by flow cytometry, plasma level of adenosine, IL-6 (interleukin-6) and EGF (epidermal growth factor), and multi-omics profiling at 12 weeks.
Results:
After 12 weeks, brachial flow-mediated dilation was significantly increased in the ticagrelor group compared with the aspirin group (ticagrelor: 3.48±3.48% versus aspirin: -1.26±2.85%, treatment effect 4.73 [95% CI, 3.85-5.62], P<0.001). Nevertheless ticagrelor treatment for 12 weeks had no significant effect on platelet activation markers, circulating endothelial progenitor cell count or plasma level of adenosine, IL-6, and EGF (all P>0.05). Multi-omics pathway assessment revealed that changes in the metabolism and biosynthesis of amino acids (cysteine and methionine metabolism; phenylalanine, tyrosine, and tryptophan biosynthesis) and phospholipids (glycerophosphoethanolamines and glycerophosphoserines) were associated with improved brachial artery flow-mediated dilation in the ticagrelor group.
Conclusions:
In patients with prior acute coronary syndrome, ticagrelor 60 mg BD monotherapy significantly improved brachial flow-mediated dilation compared with aspirin monotherapy and was associated with significant changes in metabolomic and lipidomic signatures.
Registration:
URL: https://www.
Clinicaltrials:
gov; Unique identifier: NCT03881943.
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