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      Effect of ticagrelor on the serum level of hs-CRP, ESM-1 and short-term prognosis of patients with acute STEMI

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          Abstract

          The aim of the present study was to observe and investigate the changes in the serum level of high-sensitivity C-reactive protein (hs-CRP), the endothelial cell-specific molecule-1 (ESM-1) and short-term prognosis of patients with ST-segment elevation myocardial infarction (STEMI) treated by ticagrelor. We enrolled 107 patients with acute STEMI who were admitted in the Department of Cardiology for the first time with occurrence of symptoms, and we successfully performed emergency operation of percutaneous coronary intervention. The patients were divided into two groups, 54 patients in the ticagrelor group (treatment group) and 53 patients in the clopidogrel group (control group), according to the administration of ticagrelor or clopidogrel in dual anti-platelet therapy. Then, we observed the changes at the time of admission, at 24 h, and 4th and 7th day after administration and investigated the correlations between them and the effect of ticagrelor on the short-term prognosis of acute STEMI patients. Significant increases of the serum levels of hs-CRP and ESM-1 were seen in patients of the two groups 24 h after administration of drugs with statistically significant differences between the groups (P<0.05), and on the 4th and 7th day we found a downward trend with statistically significant differences (P<0.05). The level of ESM-1 enhanced the increase of hs-CRP, indicating there was a positive correlation between ESM-1 and hs-CRP (r=0.535, P<0.001). A comparison of the occurrence rates of ischemic outcome event, bleeding and overall adverse events between the two groups yielded no statistically significant difference (P>0.05). In conclusion, the present study demonstrates that ticagrelor can reduce the prevalence of inflammatory reactions rapidly and stabilize the functions of vascular endothelium to improve the stability of atherosclerosis plaque and decrease the occurrence rate of thrombosis as well as ischemic outcome event without any obvious increase in the risk of bleeding. Thus, ticagrelor should be recommended in clinical practices for the treatment of patients with STEMI.

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          Fibrinolysis or primary PCI in ST-segment elevation myocardial infarction.

          It is not known whether prehospital fibrinolysis, coupled with timely coronary angiography, provides a clinical outcome similar to that with primary percutaneous coronary intervention (PCI) early after acute ST-segment elevation myocardial infarction (STEMI). Among 1892 patients with STEMI who presented within 3 hours after symptom onset and who were unable to undergo primary PCI within 1 hour, patients were randomly assigned to undergo either primary PCI or fibrinolytic therapy with bolus tenecteplase (amended to half dose in patients ≥75 years of age), clopidogrel, and enoxaparin before transport to a PCI-capable hospital. Emergency coronary angiography was performed if fibrinolysis failed; otherwise, angiography was performed 6 to 24 hours after randomization. The primary end point was a composite of death, shock, congestive heart failure, or reinfarction up to 30 days. The primary end point occurred in 116 of 939 patients (12.4%) in the fibrinolysis group and in 135 of 943 patients (14.3%) in the primary PCI group (relative risk in the fibrinolysis group, 0.86; 95% confidence interval, 0.68 to 1.09; P=0.21). Emergency angiography was required in 36.3% of patients in the fibrinolysis group, whereas the remainder of patients underwent angiography at a median of 17 hours after randomization. More intracranial hemorrhages occurred in the fibrinolysis group than in the primary PCI group (1.0% vs. 0.2%, P=0.04; after protocol amendment, 0.5% vs. 0.3%, P=0.45). The rates of nonintracranial bleeding were similar in the two groups. Prehospital fibrinolysis with timely coronary angiography resulted in effective reperfusion in patients with early STEMI who could not undergo primary PCI within 1 hour after the first medical contact. However, fibrinolysis was associated with a slightly increased risk of intracranial bleeding. (Funded by Boehringer Ingelheim; ClinicalTrials.gov number, NCT00623623.).
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            ESM-1 is a novel human endothelial cell-specific molecule expressed in lung and regulated by cytokines.

            We here report the identification of a novel human endothelial cell-specific molecule (called ESM-1) cloned from a human umbilical vein endothelial cell (HUVEC) cDNA library. Constitutive ESM-1 gene expression (as demonstrated by Northern blot and reverse transcription-polymerase chain reaction analysis) was found in HUVECs but not in the other human cell lines tested. The cDNA sequence contains an open reading frame of 552 nucleotides and a 1398-nucleotide 3'-untranslated region including several domains involved in mRNA instability and five putative polyadenylation consensus sequences. The deduced 184-amino acid sequence defines a cysteine-rich protein with a functional NH2-terminal hydrophobic signal sequence. Searches in several data bases confirmed the unique identity of this sequence. A rabbit immune serum raised against the 14-kDa COOH-terminal peptide of ESM-1 immunoprecipitated a 20-kDa protein only in ESM-1-transfected COS cells. Immunoblotting and immunoprecipitation of HUVEC lysates revealed a specific 20-kDa band corresponding to ESM-1. In addition, constitutive ESM-1 gene expression was shown to be tissue-restricted to the human lung. Southern blot analysis suggests that a single gene encodes ESM-1. A time-dependent up-regulation of ESM-1 mRNA was seen after addition of tumor necrosis factor alpha (TNFalpha) or interleukin (IL)-1beta but not with IL-4 or interferon gamma (IFNgamma) alone. In addition, when IFNgamma was combined with TNFalpha, IFNgamma inhibited the TNFalpha-induced increase of ESM-1 mRNA level. These data suggest that ESM-1 may have potent implications in the areas of vascular cell biology and human lung physiology.
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              Ticagrelor versus clopidogrel in patients with acute coronary syndromes intended for non-invasive management: substudy from prospective randomised PLATelet inhibition and patient Outcomes (PLATO) trial

              Objective To evaluate efficacy and safety outcomes in patients in the PLATelet inhibition and patient Outcomes (PLATO) trial who at randomisation were planned for a non-invasive treatment strategy. Design Pre-specified analysis of pre-randomisation defined subgroup of prospective randomised clinical trial. Setting 862 centres in 43 countries. Participants 5216 (28%) of 18 624 patients admitted to hospital for acute coronary syndrome who were specified as planned for non-invasive management. Interventions Randomised treatment with ticagrelor (n=2601) versus clopidogrel (2615). Main outcome measurements Primary composite end point of cardiovascular death, myocardial infarction, and stroke; their individual components; and PLATO defined major bleeding during one year. Results 2183 (41.9%) patients had coronary angiography during their initial hospital admission, 1065 (20.4%) had percutaneous coronary intervention, and 208 (4.0%) had coronary artery bypass surgery. Cumulatively, 3143 (60.3%) patients had been managed non-invasively by the end of follow-up. The incidence of the primary end point was lower with ticagrelor than with clopidogrel (12.0% (n=295) v 14.3% (346); hazard ratio 0.85, 95% confidence interval 0.73 to 1.00; P=0.04). Overall mortality was also lower (6.1% (147) v 8.2% (195); 0.75, 0.61 to 0.93; P=0.01). The incidence of total major bleeding (11.9% (272) v 10.3% (238); 1.17, 0.98 to 1.39; P=0.08) and non-coronary artery bypass grafting related major bleeding (4.0% (90) v 3.1% (71); 1.30, 0.95 to 1.77; P=0.10) was numerically higher with ticagrelor than with clopidogrel. Conclusions In patients with acute coronary syndrome initially intended for non-invasive management, the benefits of ticagrelor over clopidogrel were consistent with those from the overall PLATO results, indicating the broad benefits of P2Y12 inhibition with ticagrelor regardless of intended management strategy. Trial registration Clinical trials NCT00391872.
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                Author and article information

                Journal
                Exp Ther Med
                Exp Ther Med
                ETM
                Experimental and Therapeutic Medicine
                D.A. Spandidos
                1792-0981
                1792-1015
                February 2017
                21 December 2016
                21 December 2016
                : 13
                : 2
                : 604-608
                Affiliations
                [1 ]Department of Cardiology, Xuzhou Central Hospital, The Affiliated Hospital of Southeast University, Xuzhou, Jiangsu 221009, P.R. China
                [2 ]Department of Cardiology, The First Affiliated Hospital, Soochow University, Suzhou, Jiangsu 215006, P.R. China
                [3 ]Department of Geriatrics, Changhai Hospital of The Second Military Medical University, Shanghai 200433, P.R. China
                [4 ]Department of Cardiology, People's Hospital of Ganzhou, Ganzhou, Jiangxi 341000, P.R. China
                Author notes
                Correspondence to: Dr Qiang Fu, Department of Cardiology, Xuzhou Central Hospital, The Affiliated Hospital of Southeast University, 199 Jiefang Road, Xuzhou, Jiangsu 221009, P.R. China, E-mail: pennsylwestern@ 123456163.com
                Dr Xiang-Jun Yang, Department of Cardiology, The First Affiliated Hospital, Soochow University, 188 Shizi Street, Suzhou, Jiangsu 215006, P.R. China, E-mail: yang_xiangjun@ 123456163.com
                Article
                ETM-0-0-3987
                10.3892/etm.2016.3987
                5348695
                28352337
                32bf2442-9306-4060-b56d-5b355b137545
                Copyright: © Wei et al.

                This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.

                History
                : 22 August 2016
                : 14 November 2016
                Categories
                Articles

                Medicine
                ticagrelor,acute st-segment elevation myocardial infarction,percutaneous coronary intervention,high-sensitivity c-reactive protein,endothelial cell-specific molecule-1

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