| 21. |
- Nelson, Thomas A, et al.
(författare)
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Differential effect of clopidogrel and ticagrelor on leukocyte count in relation to patient characteristics, biomarkers and genotype : a PLATO substudy.
- 2022
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Ingår i: Platelets. - : Taylor & Francis. - 0953-7104 .- 1369-1635. ; 33:3, s. 425-431
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Tidskriftsartikel (refereegranskat)abstract
- Inflammation plays a key role in cardiovascular disease by contributing to atherothrombosis. The PLATelet inhibition and patient Outcomes (PLATO) study (NCT00391872) compared ticagrelor to clopidogrel in patients with acute coronary syndromes and demonstrated fewer cardiovascular events with ticagrelor but lower white blood cell counts (WBC) with clopidogrel. In this further analysis of the PLATO biomarker substudy, we assessed associations between WBC and clinical characteristics, biomarker levels, and CYP2C19 polymorphisms.On-treatment mean (SD) WBC in the clopidogrel group was mildly reduced at each stage of follow-up compared with either the ticagrelor group (1 month: 7.27 (2.1) and 7.67 (2.23) x109/L for clopidogrel and ticagrelor, respectively; p < .001) or following cessation of clopidogrel (7.23 (1.97) x109/L, at 6 months vs 7.56 (2.28) x109/L after treatment cessation; P < .001). This occurred independently of baseline biomarkers and CYP2C19 genotype (where known). Adjusting for clinical characteristics and other biomarkers, no significant interaction was detected between clinical risk factors and the observed effect of clopidogrel on WBC.Clopidogrel weakly suppresses WBC, independent of clinical characteristics, baseline inflammatory biomarker levels, and CYP2C19 genotype. Further work is required to determine the mechanism for this effect and whether it contributes to clopidogrel's efficacy as well as therapeutic interaction with anti-inflammatory drugs.
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| 22. |
- Storey, Robert F., et al.
(författare)
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Pharmacodynamics, pharmacokinetics, and safety of single-dose subcutaneous administration of selatogrel, a novel P2Y12 receptor antagonist, in patients with chronic coronary syndromes
- 2020
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Ingår i: European Heart Journal. - : Oxford University Press (OUP). - 0195-668X .- 1522-9645. ; 41:33, s. 3132-3140
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Tidskriftsartikel (refereegranskat)abstract
- Aims To study the pharmacodynamics and pharmacokinetics of selatogrel, a novel P2Y(12) receptor antagonist for subcutaneous administration, in patients with chronic coronary syndromes (CCS). Methods and results In this double-blind, randomized study of 345 patients with CCS on background oral antiplatelet therapy, subcutaneous selatogrel (8 mg, n = 114; or 16 mg, n = 115) was compared with placebo (n = 116) (ClinicalTrials.gov: NCT03384966). Platelet aggregation was assessed over 24 h (VerifyNow assay) and 8 h (light transmittance aggregometry; LTA). Pharmacodynamic responders were defined as patients having P2Y(12) reaction units (PRU) <100 at 30 min post-dose and lasting >= 3 h. At 30 min post-dose, 89% of patients were responders to selatogrel 8 mg, 90% to selatogrel 16 mg, and 16% to placebo (P < 0.0001). PRU values (mean standard deviation) were 10 +/- 25 (8 mg), 4 +/- 10 (16 mg), and 163 +/- 73 (placebo) at 15 min and remained <100 up to 8 h for both doses, returning to pre-dose or near pre-dose levels by 24 h post-dose. LTA data showed similarly rapid and potent inhibition of platelet aggregation. Selatogrel plasma concentrations peaked similar to 30 min post-dose. Selatogrel was safe and well-tolerated with transient dyspnoea occurring overall in 7% (16/229) of patients (95% confidence interval: 4-11%). Conclusions Selatogrel was rapidly absorbed following subcutaneous administration in CCS patients, providing prompt, potent, and consistent platelet P2Y(12) inhibition sustained for >= 8 h and reversible within 24 h. Further studies of subcutaneous selatogrel are warranted in clinical scenarios where rapid platelet inhibition is desirable.
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| 23. |
- Sumaya, Wael, et al.
(författare)
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Impaired Fibrinolysis Predicts Adverse Outcome in Acute Coronary Syndrome Patients with Diabetes : A PLATO Sub-Study
- 2020
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Ingår i: Thrombosis and Haemostasis. - : GEORG THIEME VERLAG KG. - 0340-6245 .- 2567-689X. ; 120:3, s. 412-422
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Tidskriftsartikel (refereegranskat)abstract
- Hypofibrinolysis is a key abnormality in diabetes but the role of impaired clot lysis in predicting vascular events and mortality in this population is yet to be determined. We aimed to investigate the relationship between fibrin clot properties and clinical outcomes in patients with diabetes and recent acute coronary syndrome (ACS). Plasma samples were collected at hospital discharge from 974 ACS patients with diabetes randomised to clopidogrel or ticagrelor in the PLATO trial. A validated turbidimetric assay was employed to study fibrin clot lysis and maximum turbidity. One-year rates of cardiovascular (CV) death, spontaneous myocardial infarction (MI) and PLATO-defined major bleeding events were assessed after sample collection. Hazard ratios (HRs) were determined using Cox proportional analysis. After adjusting for CV risk factors, each 50% increase in lysis time was associated with increased risk of CV death/MI (HR 1.21; 95% confidence interval [CI] 1.02-1.44; p = 0.026) and CV death alone (HR 1.38; 1.08-1.76; p = 0.01). Similarly, each 50% increase in maximum turbidity was associated with increased risk of CV death/MI (HR 1.25; 1.02-1.53; p = 0.031) and CV death alone (HR 1.49; 1.08-2.04; p = 0.014). The relationship between lysis time and the combined outcome of CV death and MI remained significant after adjusting for multiple prognostic vascular biomarkers ( p = 0.034). Neither lysis time nor maximum turbidity was associated with major bleeding events. Impaired fibrin clot lysis predicts 1-year CV death and MI in diabetes patients following ACS.
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| 24. |
- Ueland, Thor, et al.
(författare)
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ALCAM predicts future cardiovascular death in acute coronary syndromes : Insights from the PLATO trial
- 2020
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Ingår i: Atherosclerosis. - : Elsevier. - 0021-9150 .- 1879-1484. ; 293, s. 35-41
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND AND AIMS: Activated leukocyte cell adhesion molecule (ALCAM) is upregulated during inflammation and involved in transmigration of leukocytes and T-cell activation. We hypothesized that ALCAM might be associated with recurrent events in patients with acute coronary syndromes (ACS).METHODS: ALCAM was measured in serum obtained on admission, at discharge, 1 month and 6 months in a subgroup of 5165 patients admitted with ACS and included in the PLATelet inhibition and patient Outcomes (PLATO) trial (NCT00391872). The association between ALCAM and the composite endpoint and its components, including cardiovascular (CV) death, non-procedural spontaneous myocardial infarction (MI) or stroke during 1-year follow-up, was assessed by Cox proportional hazards models with incremental addition of clinical risk factors and biomarkers (including high-sensitivity troponin T, N-terminal pro-B-type natriuretic peptide and growth differentiation factor-15).RESULTS: The median (Q1-Q3) concentration of ALCAM at admission was 97 (80-116) ng/mL. A 50% higher level of ALCAM on admission was associated with a hazard ratio (HR) of 1.16 (95% confidence interval [1.00-1.34] p = 0.043) for the composite endpoint in fully adjusted analysis, mainly driven by the association with CV death (HR 1.45 [1.16-1.82] p = 0.0012).CONCLUSIONS: In patients with ACS, admission level of ALCAM was independently associated with adverse outcome including CV death even after adjustment for established inflammatory and cardiac biomarkers.
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| 25. |
- Valgimigli, Marco, et al.
(författare)
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Antithrombotic treatment strategies in patients with established coronary atherosclerotic disease
- 2023
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Ingår i: European Heart Journal - Cardiovascular Pharmacotherapy. - : Oxford University Press. - 2055-6837 .- 2055-6845. ; 9:5, s. 462-496
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Tidskriftsartikel (refereegranskat)abstract
- Multiple guidelines and consensus papers have addressed the role of antithrombotic strategies in patients with established coronary artery disease (CAD). Since evidence and terminology continue to evolve, the authors undertook a consensus initiative to guide clinicians to select the optimal antithrombotic regimen for each patient. The aim of this document is to provide an update for clinicians on best antithrombotic strategies in patients with established CAD, classifying each treatment option in relation to the number of antithrombotic drugs irrespective of whether the traditional mechanism of action is expected to mainly inhibit platelets or coagulation cascade. With the aim to reach comprehensiveness of available evidence, we systematically reviewed and performed meta-analyses by means of both direct and indirect comparisons to inform the present consensus document.
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