Stronger inhibitory effects of ticagrelor plus aspirin compared with clopidogrel plus aspirin on arachidonic acid induced platelet aggregation in patients with acute coronary syndrome with PCI

2020 ◽  
pp. 1-7
Author(s):  
Zhichao Dong ◽  
Hengbo Zhai ◽  
Lifei Pan ◽  
Bo Zhang
Keyword(s):  
Acute Coronary Syndrome ◽  
Arachidonic Acid ◽  
Platelet Aggregation ◽  
Adenosine Diphosphate ◽  
Platelet Inhibition ◽  
Inhibit Platelet Aggregation ◽  
Inhibitory Effects ◽  
Coronary Syndrome ◽  
Adp Receptor

Abstract Antagonists of the adenosine diphosphate (ADP) receptor, P2Y12 may inhibit platelet aggregation resulting from stimulation with arachidonic acid (AA). The potent P2Y12 blocker, ticagrelor has greater anti-platelet effects than clopidogrel. We explored the effects of ticagrelor versus clopidogrel on mean maximum aggregation ratios (MAR%) in response to AA stimulation in patients receiving conventional aspirin dosages. A total of 613 acute coronary syndrome (ACS) patients were followed from October 2017 to October 2018. At the 1- and 6-month follow-up visit, mean AA-MAR% was lower in the ticagrelor group when compared with the clopidogrel group (28.9% vs. 31.7%, 28.4% vs. 31.0%, P<0.001 and P=0.001, respectively). BARC1-2 bleeding occurred with greater frequency with ticagrelor rather than clopidogrel treated patients (29.3% vs. 9.5%, P<0.001; 23.5% vs. 9.3%, P<0.001). Excessive platelet inhibition and decreased AA-MAR% were considered the main reasons for the severe subcutaneous/dermal bleeding in ticagrelor treated patients. Continuous...

Diurnal Variability of On-Treatment Platelet Reactivity in Clopidogrel versus Prasugrel Treated Acute Coronary Syndrome Patients: A Pre-Specified TROPICAL-ACS Sub-Study

2019 ◽  
Vol 119 (04) ◽  
pp. 660-667 ◽  
Author(s):  
Matthias Freynhofer ◽  
Ralph Hein-Rothweiler ◽  
Paul Haller ◽  
Daniel Aradi ◽  
Döme Dézsi ◽  
...  
Keyword(s):  
Acute Coronary Syndrome ◽  
Platelet Reactivity ◽  
Adenosine Diphosphate ◽  
Coronary Intervention ◽  
Early Morning ◽  
Platelet Inhibition ◽  
Control Group ◽  
Diurnal Variability ◽  
Coronary Syndrome ◽  
Adp Receptor

AbstractLong-term evidence supports a clustering of cardiovascular events in the early morning and smaller mechanistic studies in aspirin-treated patients have shown increased platelet reactivity at the end of the dosing interval. Comparative pharmacodynamic analyses for different adenosine diphosphate (ADP) receptor inhibitors in percutaneous coronary intervention-treated acute coronary syndrome (ACS) patients are lacking and this pre-specified analysis from the randomized Testing Responsiveness To Platelet Inhibition On Chronic Antiplatelet Treatment For Acute Coronary Syndromes (TROPICAL-ACS) trial aimed for the first time at investigating diurnal variability of on-treatment platelet reactivity in clopidogrel versus prasugrel treated patients. TROPICAL-ACS randomized 2,610 ACS patients to either treatment with prasugrel (control group) or to a platelet function testing-guided de-escalation of anti-platelet treatment with a switch to clopidogrel (guided de-escalation group). This study design enabled a diurnal comparison of on-prasugrel versus on-clopidogrel treatment platelet reactivity under steady-state conditions. For 2,526 patients (97%), both the exact time of blood sampling and the ADP-induced platelet aggregation value (in units, Multiplate analyser) were available. Platelet reactivity in patients on clopidogrel (n = 1,265) was higher and subject to significant diurnal variability (p = 0.019) with a peaking of platelet reactivity in the early morning (5–10 a.m.). In prasugrel-treated patients (n = 1,261), there was no sign for diurnal variability (p = 0.174) or a peaking of platelet reactivity in the morning. The potent ADP receptor inhibitor prasugrel is not subject to diurnal variability while we observed a significant diurnal variability of on-clopidogrel platelet reactivity. The clinical impact of this observation may differ for patients with and without an adequate response to clopidogrel treatment and the issue of diurnal variability of platelet reactivity in ACS patients warrants further investigation.

Effects of clopidogrel vs. prasugrel vs. ticagrelor on endothelial function, inflammatory parameters, and platelet function in patients with acute coronary syndrome undergoing coronary artery stenting: a randomized, blinded, parallel study

2020 ◽  
Vol 41 (33) ◽  
pp. 3144-3152 ◽  
Author(s):  
Boris Schnorbus ◽  
Andreas Daiber ◽  
Kerstin Jurk ◽  
Silke Warnke ◽  
Jochem Koenig ◽  
...  
Keyword(s):  
Acute Coronary Syndrome ◽  
Endothelial Function ◽  
Adenosine Diphosphate ◽  
Platelet Inhibition ◽  
Clinical Parameter ◽  
Mean Difference ◽  
Low Flow ◽  
Flow Mediated Dilation ◽  
Coronary Syndrome ◽  
The Impact

Abstract Aims In a randomized, parallel, blinded study, we investigate the impact of clopidogrel, prasugrel, or ticagrelor on peripheral endothelial function in patients undergoing stenting for an acute coronary syndrome. Methods and results The primary endpoint of the study was the change in endothelium-dependent flow-mediated dilation (FMD) following stenting. A total of 90 patients (age 62 ± 9 years, 81 males, 22 diabetics, 49 non-ST elevation myocardial infarctions) were enrolled. There were no significant differences among groups in any clinical parameter. Acutely before stenting, all three drugs improved FMD without differences between groups (P = 0.73). Stenting blunted FMD in the clopidogrel and ticagrelor group (both P &lt; 0.01), but not in the prasugrel group. During follow-up, prasugrel was superior to clopidogrel [mean difference 2.13, 95% confidence interval (CI) 0.68–3.58; P = 0.0047] and ticagrelor (mean difference 1.57, 95% CI 0.31–2.83; P = 0.0155), but this difference was limited to patients who received the study therapy 2 h before stenting. Ticagrelor was not significantly superior to clopidogrel (mean difference 0.55, 95% CI −0.73 to 1.82; P = 0.39). No significant differences were seen among groups for low-flow-mediated dilation. Plasma interleukin (IL)-6 (P = 0.02 and P = 0.01, respectively) and platelet aggregation reactivity in response to adenosine diphosphate (P = 0.002 and P = 0.035) were lower in the prasugrel compared to clopidogrel and ticagrelor group. Conclusion As compared to ticagrelor and clopidogrel, therapy with prasugrel in patients undergoing stenting for an acute coronary syndrome is associated with improved endothelial function, stronger platelet inhibition, and reduced IL-6 levels, all of which may have prognostic implications. This effect was lost in patients who received the study medication immediately after stenting. EUDRACT-No 2011-005305-73

Prasugrel compared with high-dose clopidogrel in acute coronary syndrome

2010 ◽  
Vol 103 (01) ◽  
pp. 213-223 ◽  
Author(s):  
Georgios Sideris ◽  
Remy Cohen ◽  
Catherine Meuleman ◽  
Claire Bal dit Sollier ◽  
Olivier Barthélémy ◽  
...  
Keyword(s):  
Acute Coronary Syndrome ◽  
Poor Response ◽  
Adenosine Diphosphate ◽  
Coronary Intervention ◽  
Platelet Inhibition ◽  
High Dose ◽  
Coronary Syndrome ◽  
Percutaneous Coronary ◽  
St Elevation ◽  
To Receive

SummaryCompared with the approved dose regimen of clopidogrel (300-mg loading dose [LD], 75-mg maintenance dose [MD]), prasugrel has been demonstrated to reduce ischaemic events in patients with acute coronary syndrome (ACS) undergoing percutaneous coronary intervention (PCI). In ACS, antiplatelet effects of a prasugrel MD regimen have not been previously compared with either a higher clopidogrel MD or after switching from a higher clopidogrel LD. The objective of this study was to evaluate the antiplatelet effect of a prasugrel 10-mg MD versus a clopidogrel 150-mg MD in patients with ACS who had received a clopidogrel 900-mg LD. Patients with non-ST elevation ACS, treated with aspirin and a clopidogrel 900-mg LD, were randomised within 24 hours post-LD to receive a prasugrel 10-mg or clopidogrel 150-mg MD. After 14 days of the initial MD, subjects switched to the alternative treatment for 14 days. The primary endpoint compared maximum platelet aggregation (MPA, 20 μM adenosine diphosphate [ADP]) between prasugrel and clopidogrel MDs for both periods. Responder analyses between treatments were performed using several platelet-function methods. Of 56 randomised subjects, 37 underwent PCI. MPA was 26.2% for prasugrel 10 mg and 39.1% for clopidogrel 150 mg (p<0.001). The prasugrel MD regimen reduced MPA from the post-900-mg LD level (41.2% to 29.1%, p=0.003). Poor response ranged from 0% to 6% for prasugrel 10 mg and 4% to 34% for clopidogrel 150 mg. Thus, in ACS patients a prasugrel 10-mg MD regimen resulted in significantly greater platelet inhibition than clopidogrel at twice its approved MD or a 900-mg LD.

Smoking and outcomes following guided de-escalation of antiplatelet treatment in acute coronary syndrome patients: a substudy from the randomized TROPICAL-ACS trial

2019 ◽  
Vol 6 (6) ◽  
pp. 372-381 ◽  
Author(s):  
Martin Orban ◽  
Dietmar Trenk ◽  
Tobias Geisler ◽  
Johannes Rieber ◽  
Martin Hadamitzky ◽  
...  
Keyword(s):  
Acute Coronary Syndrome ◽  
Platelet Aggregation ◽  
Clinical Outcomes ◽  
Smoking Status ◽  
Adenosine Diphosphate ◽  
Antiplatelet Drug ◽  
Control Group ◽  
Antiplatelet Treatment ◽  
Coronary Syndrome ◽  
The Impact

Abstract Aims Prior analyses disclosed variations in antiplatelet drug response and clinical outcomes between smokers and non-smokers, thus the safety and efficacy of any dual antiplatelet therapy (DAPT) de-escalation strategy may differ in relation to smoking status. Hence, we assessed the impact of smoking on clinical outcomes and adenosine diphosphate-induced platelet aggregation following guided de-escalation of DAPT in invasively managed acute coronary syndrome (ACS) patients. Methods and results The multicentre TROPICAL-ACS trial randomized 2610 biomarker-positive ACS patients 1:1 to standard treatment with prasugrel for 12 months (control group) or a platelet function testing guided de-escalation of DAPT. Current smokers (n = 1182) showed comparable event rates between study groups [6.6% vs. 6.6%; hazard ratio (HR) 1.0, 95% confidence interval (CI) 0.64–1.56, P &gt; 0.99]. In non-smokers (n = 1428), a guided DAPT de-escalation was associated with a lower 1-year incidence of the primary endpoint [cardiovascular death, myocardial infarction, stroke, or bleeding ≥ Grade 2 according to Bleeding Academic Research Consortium (BARC) criteria] compared with control group patients (7.9% vs. 11.0%; HR 0.71, 95% CI 0.50–0.99, P = 0.048). This reduction was mainly driven by a lower rate of BARC ≥ Grade 2 bleedings (5.2% vs. 7.7%; HR 0.68, 95% CI 0.45–1.03, P = 0.066). There was no significant interaction of smoking status with treatment effects of guided DAPT de-escalation (Pint = 0.23). Adenosine diphosphate-induced platelet aggregation values were higher in current smokers [median 28 U, interquartile range (IQR: 20–40)] vs. non-smoker [median 24 U (16–25), P &lt; 0.0001] in the control group and in current smokers [median 42 U, IQR (27–68)] vs. non-smoker [median 37 U, IQR (25–55), P &lt; 0.001] in the monitoring group. Conclusion Guided DAPT de-escalation appears to be equally safe and effective in smokers and non-smokers. Regardless of smoking status and especially for those patients deemed unsuitable for 1 year of potent platelet inhibition this DAPT strategy might be used as an alternative antiplatelet treatment regimen.

scholarly journals Validation of a New ELISA-Based Vasodilator-Associated Stimulated Phosphoprotein Phosphorylation Assay to Assess Platelet Reactivity Index in a Chinese Population

2017 ◽  
Vol 24 (3) ◽  
pp. 452-461 ◽  
Author(s):  
Peng Ding ◽  
Yujie Wei ◽  
Nana Chen ◽  
Huiliang Liu
Keyword(s):  
Acute Coronary Syndrome ◽  
Healthy Volunteers ◽  
Chinese Population ◽  
Platelet Reactivity ◽  
Adenosine Diphosphate ◽  
Coronary Intervention ◽  
Platelet Inhibition ◽  
Reactivity Index ◽  
Enzyme Linked Immunosorbent Assay ◽  
Coronary Syndrome

The level of platelet reactivity during P2Y12-adenosine diphosphate receptor antagonist is associated with ischemic and bleeding risks following percutaneous coronary intervention in acute coronary syndrome. Determining platelet reactivity inhibition may be valuable for confirming effective platelet inhibition for individual patients and identifying patients at risk of bleeding. The enzyme-linked immunosorbent assay (ELISA)-based vasodilator-stimulated phosphoprotein (VASP) assay offers unique advantages over other methods and has not been used in the Chinese population. We enrolled 10 healthy volunteers and 54 patients with acute coronary syndrome. The volunteers received no treatment, and patients were administered a loading dose of clopidogrel or ticagrelor. The platelet reactivity index (PRI) was measured using flow cytometry (FC)-VASP and ELISA-VASP at baseline and 8-hour postloading dose. Blood samples of healthy volunteers and clopidogrel- or ticagrelor-treated patients were frozen and stored for 1, 2, and 4 weeks after initial activation. All frozen samples were tested using ELISA-VASP. The PRI assessed by FC-VASP and ELISA-VASP correlated well showing a high degree of consistency in identifying high or low on-treatment platelet reactivity. No significant time-dependent changes in PRI results were observed in frozen samples stored up to 4 weeks compared to nonfrozen samples. The PRI of ticagrelor-treated patients was lower than that of clopidogrel-treated patients. The ELISA-VASP effectively assesses the PRI, and results obtained from frozen specimens are unaffected by storage and shipment prior to assay. Ticagrelor was superior to clopidogrel in decreasing the PRI.

Platelet Inhibition by Abciximab Bolus-Only Administration and Oral ADP Receptor Antagonist Loading in Acute Coronary Syndrome Patients: The Blocking and Bridging Strategy

2013 ◽  
Vol 132 (1) ◽  
pp. e36-e41 ◽  
Author(s):  
Günter Christ ◽  
Thomas Hafner ◽  
Jolanta M. Siller-Matula ◽  
Marcel Francesconi ◽  
Katharina Grohs ◽  
...  
Keyword(s):  
Acute Coronary Syndrome ◽  
Receptor Antagonist ◽  
Platelet Inhibition ◽  
Coronary Syndrome ◽  
Adp Receptor ◽  
Bridging Strategy

P824The clinical impact of polyunsaturated fatty acid on clinical outcomes in acute coronary syndrome with dyslipidemia: HIJ-PROPER sub-analysis

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
M Nakawaza ◽  
H Arashi ◽  
H Nomura ◽  
E Kawada-Watanabe ◽  
M Ogiso ◽  
...  
Keyword(s):  
Acute Coronary Syndrome ◽  
Arachidonic Acid ◽  
Eicosapentaenoic Acid ◽  
Clinical Outcomes ◽  
Primary Endpoint ◽  
Lipid Lowering ◽  
Lipid Lowering Therapy ◽  
Coronary Syndrome ◽  
Lowering Therapy

Abstract Background Polyunsaturated fatty acids, especially omega-3 and -6 series, are key essential nutrients that play an important role in humans to maintain cell membranes and function. A recent randomized trial reported that adding eicosapentaenoic acid (EPA) to statins was beneficial to cardiovascular disease patients who had a residual risk factor. Further, several studies have reported that the low baseline value for EPA to arachidonic acid (AA) ratio is related to worse clinical outcome and plaque vulnerability in coronary artery disease patients. However, effects of baseline EPA/AA ratio on clinical outcomes in ACS patients have not been thoroughly evaluated. Objectives This study aimed to examine the impact of baseline eicosapentaenoic acid to arachidonic acid (EPA/AA) ratio on clinical outcomes of acute coronary syndrome (ACS) patients and how lipid-lowering therapy affects serum EPA/AA levels in these patients. Methods This is a sub-analysis of HIJ-PROPER assessing the effect of aggressive low-density lipoprotein cholesterol (LDL-C)-lowering treatment with pitavastatin+ezetimibe in 1,734 ACS patients with dyslipidemia. Patients were divided into two groups based on EPA/AA level on admission (cut-off: 0.34 μg/mL; median of baseline EPA/AA level) and clinical outcomes were examined. Results Percent reduction of LDL-C from baseline to follow-up and mean LDL-C level during follow-up were similar regardless of baseline EPA/AA ratio. In the low EPA/AA group, the Kaplan–Meier estimate for the primary endpoint at 3 years was 27.2% in the pitavastatin+ezetimibe group, compared with 36.6% in the pitavastatin-monotherapy group [hazard ratio (HR), 0.69; 95% confidence interval (CI), 0.52–0.93; P=0.015). However, in the high EPA/AA group, there was no significant reduction in the primary endpoint by pitavastatin+ezetimibe therapy (HR, 0.92; 95% CI, 0.70–1.20; P=0.52). Conclusions Aggressive lipid-lowering therapy with ezetimibe had a positive effect on clinical outcomes in the low EPA/AA group of ACS patients with dyslipidemia, but not in the high EPA/AA group. This effect was independent of LDL-C reduction and suggests that EPA/AA measurement on admission in ACS patients contributes to a “personalized” lipid-lowering approach.

Platelet Aggregation Induced by a Synthetase-Like Substance and Phospholipase-A.

1975 ◽  
Author(s):  
S. G. Iatridis ◽  
P. G. Iatridis ◽  
S. G. Markidou ◽  
B. H. Ragatz
Keyword(s):  
Arachidonic Acid ◽  
Platelet Aggregation ◽  
Adenosine Diphosphate ◽  
Phospholipase A ◽  
Second Phase ◽  
Inhibit Platelet Aggregation ◽  
Phase Type ◽  
Irreversible Aggregation ◽  
Cyclic Endoperoxide ◽  
Aggregation Of Platelets

Platelets contain arachidonic acid-bearing phospholipids and phospholipase-A (Phl-A); it has been suggested that exposure of these substances to each other by stimuli, such as thrombin or adenosine diphosphate (ADP), would result in liberation of arachidonic acid (AA), which is the precursor of cyclic endoperoxide; a factor causing irreversible aggregation of platelets.By using a saline eluate of a polyurethane (SPU, -polyester elastomer of the thermoplastic type-, secured by exposing saline for two minutes to the inner surface of a polyurethane bag) we observed that platelet (human PRP) aggregation (second phase type, irreversible) could be induced by Phl-A plus SPU or AA plus SPU. These mixtures failed to aggregate aspirinized platelets. Aspirin, however, incubated for 10 minutes with SPU, Phl-A or AA did not inhibit platelet aggregation induced by the addition of the missing factor. In control experiments no aggregation was produced by SPU-saline, saline-Phl-A or saline-AA. SPU plus suboptimal concentrations of ADP or epinephrine induced an immediate in onset aggregation. Phl-A added in reversibly, by ADP, aggregated platelets produced a second phase of aggregation.The results show that AA which is the precursor of cyclic endoperoxide could be liberated by Phl-A. The results also provide evidence that at least two enzymes (synthetase-α and synthetase-β; α is inactive whereas β is active and can be blocked by apsirin) are involved in the process of AA activation and biosynthesis of cyclic endoperoxide.Supported by a grant from the U.S. Public Servie HL-15425.

scholarly journals Inhibitory Mechanisms of Lusianthridin on Human Platelet Aggregation

2021 ◽  
Vol 22 (13) ◽  
pp. 6846
Author(s):  
Hla Nu Swe ◽  
Boonchoo Sritularak ◽  
Ponlapat Rojnuckarin ◽  
Rataya Luechapudiporn
Keyword(s):  
Arachidonic Acid ◽  
Platelet Aggregation ◽  
Adenosine Diphosphate ◽  
Docking Studies ◽  
Secondary Wave ◽  
Inhibitory Effects ◽  
Antiplatelet Aggregation ◽  
Cyclooxygenase 1 ◽  
Cox 2 ◽  
Cox 1

Lusianthridin is a phenanthrene derivative isolated from Dendrobium venustum. Some phenanthrene compounds have antiplatelet aggregation activities via undefined pathways. This study aims to determine the inhibitory effects and potential mechanisms of lusianthridin on platelet aggregation. The results indicated that lusianthridin inhibited arachidonic acid, collagen, and adenosine diphosphate (ADP)-stimulated platelet aggregation (IC50 of 0.02 ± 0.001 mM, 0.14 ± 0.018 mM, and 0.22 ± 0.046 mM, respectively). Lusianthridin also increased the delaying time of arachidonic acid-stimulated and the lag time of collagen-stimulated and showed a more selective effect on the secondary wave of ADP-stimulated aggregations. Molecular docking studies revealed that lusianthridin bound to the entrance site of the cyclooxygenase-1 (COX-1) enzyme and probably the active region of the cyclooxygenase-2 (COX-2) enzyme. In addition, lusianthridin showed inhibitory effects on both COX-1 and COX-2 enzymatic activities (IC50 value of 10.81 ± 1.12 µM and 0.17 ± 1.62 µM, respectively). Furthermore, lusianthridin significantly inhibited ADP-induced suppression of cAMP formation in platelets at 0.4 mM concentration (p < 0.05). These findings suggested that possible mechanisms of lusianthridin on the antiplatelet effects might act via arachidonic acid-thromboxane and adenylate cyclase pathways.

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