Trial reportArteriosclerosis, thrombosis, and vascular biology2015
Platelet P2Y12 Inhibitors Reduce Systemic Inflammation and Its Prothrombotic Effects in an Experimental Human Model.
Trial report in Arteriosclerosis, thrombosis, and vascular biology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 3 registered trials, which are not on this map. Cited by 66 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
The Impact of Aspirin Dose Modification on the Innate Immune Response - Will Lower Dose Aspirin Therapy Reduce the Response to Endotoxin
REACTIC-TAVI Trial: Platelet REACtivity According to TICagrelor Dose After Transcatheter AorticValve Implantation. A Pilot Study.
Characterisation of a Novel Regimen of Very Low-dose Aspirin Combined With Rivaroxaban in Patients With Chronic Coronary Syndromes: WILL lOWer Dose Aspirin be Better With Rivaroxaban in Patients With Chronic Coronary Syndromes?
Who cites it
66 citing papers in PubMed, 130 citations in OpenAlex.
- Pre-treatment lysis time of plasma-derived fibrin clots and bleeding in patients on oral anticoagulants for atrial fibrillation in the ARISTOTLE trial.European heart journal · 2026Trial
- Effect of P2Y12 Inhibitors on Organ Support-Free Survival in Critically Ill Patients Hospitalized for COVID-19: A Randomized Clinical Trial.JAMA network open · 2023Trial
- Effect of ticagrelor and prasugrel on remote myocardial inflammation in patients with acute myocardial infarction with ST-elevation: a CMR T1 and T2 mapping study.The international journal of cardiovascular imaging · 2023Trial
- Ticagrelor inhibits platelet aggregation and reduces inflammatory burden more than clopidogrel in patients with stages 4 or 5 chronic kidney disease.Vascular pharmacology · 2023Trial
- Ticagrelor attenuates the increase of extracellular vesicle concentrations in plasma after acute myocardial infarction compared to clopidogrel.Journal of thrombosis and haemostasis : JTH · 2020Trial
- 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.Cardiovascular diabetology · 2020Trial
- Fibrin clot properties independently predict adverse clinical outcome following acute coronary syndrome: a PLATO substudy.European heart journal · 2018Trial
- Ticagrelor mitigates ischaemia-reperfusion induced vascular endothelial dysfunction in healthy young males - a randomized, single-blinded study.British journal of clinical pharmacology · 2017Trial
- Platelet homeostasis and heterogeneity in inflammation and sepsis: mechanisms, biological effects, and clinical potential.Cell communication and signaling : CCS · 2026Review
- Comparing anti-platelet and anti-thrombin therapies in the ischaemia-reperfusion injured coronary microcirculation of healthy and diabetic mice.Basic research in cardiology · 2026Article
- A cecal slurry mouse model of polymicrobial abdominal sepsis to evaluate the effects of antiplatelet agents.Research and practice in thrombosis and haemostasis · 2026Article
- Sepsis-induced immunothrombosis: from cellular crosstalk to multiple organ dysfunction.Frontiers in immunology · 2026Review
- Association between clopidogrel use and improved survival in critically ill patients with acute kidney injury: insights from MIMIC-IV database.BMC nephrology · 2025Article
- P2YBiomedicines · 2025Article
- New-onset postoperative atrial fibrillation and burden imposed by CYP2C19 metabolizer phenotype on clopidogrel in off-pump coronary artery bypass: a retrospective cohort study.Perioperative medicine (London, England) · 2025Article
- Previous Antiplatelet Therapy on Ticagrelor-Aspirin and Clopidogrel-Aspirin Efficacy in Intracranial Artery Stenosis.Journal of stroke · 2025Article
- Tandem ssDNA in neutrophil extracellular traps binds thrombin and regulates immunothrombosis.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Immunothrombosis in Sepsis: Cellular Crosstalk, Molecular Triggers, and Therapeutic Opportunities-A Review.International journal of molecular sciences · 2025Review
- The Crucial Roles of Platelets as Immune Mediators in Sepsis.Journal of inflammation research · 2025Review
- Platelets in Kawasaki disease: mediators of vascular inflammation.Nature reviews. Rheumatology · 2024Review
6 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
13 authors at 1 institution in 1 country.
Funding
Abstract
objectiveClinical studies suggest that platelet P2Y12 inhibitors reduce mortality from sepsis, although the underlying mechanisms have not been clearly defined in vivo. We hypothesized that P2Y12 inhibitors may improve survival from sepsis by suppressing systemic inflammation and its prothrombotic effects. We therefore determined whether clopidogrel and the novel, more potent P2Y12 inhibitor, ticagrelor, modify these responses in an experimental human model. APPROACH AND
resultsWe randomized 30 healthy volunteers to ticagrelor (n=10), clopidogrel (n=10), or no antiplatelet medication (controls; n=10). We examined the effect of P2Y12 inhibition on systemic inflammation, which was induced by intravenous injection of Escherichia coli endotoxin. Both P2Y12 inhibitors significantly reduced platelet-monocyte aggregate formation and peak levels of major proinflammatory cytokines, including tumor necrosis factor α, interleukin-6, and chemokine (C-C motif) ligand 2. In contrast to clopidogrel, ticagrelor also significantly reduced peak levels of IL-8 and growth colony-stimulating factor and increased peak levels of the anti-inflammatory cytokine IL-10. In addition, ticagrelor altered leukocyte trafficking. Both P2Y12 inhibitors suppressed D-dimer generation and scanning electron microscopy revealed that ticagrelor also suppressed prothrombotic changes in fibrin clot ultrastructure.
conclusionsPotent inhibition of multiple inflammatory and prothrombotic mechanisms by P2Y12 inhibitors demonstrates critical importance of platelets as central orchestrators of systemic inflammation induced by bacterial endotoxin. This provides novel mechanistic insight into the lower mortality associated with P2Y12 inhibitors in patients with sepsis in clinical studies.
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What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.