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      Comparisons between ticagrelor and clopidogrel following percutaneous coronary intervention in patients with acute coronary syndrome: a comprehensive meta-analysis

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          Abstract

          Background

          The efficacy and safety of ticagrelor following percutaneous coronary intervention for patients with acute coronary syndrome remains unclear. This study sought to evaluate clinical outcomes of ticagrelor as part of dual-antiplatelet treatment for these patients.

          Methods

          PubMed, MEDLINE, Embase, and other Internet sources were searched for eligible citations. The primary end point was major adverse cardiovascular and cerebrovascular events, consisting of cardiovascular death, myocardial infarction, and stroke. The secondary end point was the occurrence of definite/probable stent thrombosis (ST). The risk of bleeding was chosen to be the safety end point.

          Results

          Eleven clinical trials – six randomized trials and five observational trials – were finally analyzed. A tendency toward reduction in the risk of major adverse cardiovascular and cerebrovascular events was observed only with respect to ticagrelor (OR 0.83, 95% CI 0.66–1.03; P=0.091), which might have resulted from the lower risk of cardiovascular death (OR 0.78, 95% CI 0.68–0.89; P<0.001). The overall incidence of ST differed significantly between the ticagrelor group and the clopidogrel group (OR 0.74, 95% CI 0.59–0.93; P=0.009), but the risk of bleeding, regardless of major or minor bleeding, increased significantly.

          Conclusion

          As part of dual-antiplatelet treatment following percutaneous coronary intervention, ticagrelor significantly reduced the risk of cardiovascular death and ST in acute coronary syndrome patients, but at the cost of bleeding. More powerful relevant randomized trials are still warranted to guide clinical decision-making.

          Most cited references21

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          2013 ACCF/AHA guideline for the management of ST-elevation myocardial infarction: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines.

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            Thirty-year trends (1975 to 2005) in the magnitude of, management of, and hospital death rates associated with cardiogenic shock in patients with acute myocardial infarction: a population-based perspective.

            Limited information is available about potentially changing and contemporary trends in the incidence and hospital death rates of cardiogenic shock complicating acute myocardial infarction. The objectives of our study were to examine 3-decade-long trends (1975 to 2005) in the incidence rates of cardiogenic shock complicating acute myocardial infarction, patient characteristics and treatment practices associated with this clinical complication, and hospital death rates in residents of a large central New England community hospitalized with acute myocardial infarction at all area medical centers. The study population consisted of 13 663 residents of the Worcester (Mass) metropolitan area hospitalized with acute myocardial infarction at all greater Worcester medical centers during 15 annual periods between 1975 and 2005. Overall, 6.6% of patients developed cardiogenic shock during their index hospitalization. The incidence rates of cardiogenic shock remained stable between 1975 and the late 1990s but declined in an inconsistent manner thereafter. Patients in whom cardiogenic shock developed had a significantly greater risk of dying during hospitalization (65.4%) than those who did not develop cardiogenic shock (10.6%) (P<0.001). Encouraging increases in hospital survival in patients with cardiogenic shock, however, were observed from the mid-1990s to our most recent study years. Several patient demographic and clinical characteristics were associated with an increased risk for developing cardiogenic shock. Our findings indicate improving trends in the hospital prognosis associated with cardiogenic shock. Given the high death rates associated with this clinical complication, monitoring future trends in the incidence and death rates and the factors associated with an increased risk for developing cardiogenic shock remains warranted.
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              Inhibition of platelet aggregation by AZD6140, a reversible oral P2Y12 receptor antagonist, compared with clopidogrel in patients with acute coronary syndromes.

              In a substudy of DISPERSE (Dose confIrmation Study assessing anti-Platelet Effects of AZD6140 vs. clopidogRel in non-ST-segment Elevation myocardial infarction)-2, we compared the antiplatelet effects of AZD6140 and clopidogrel and assessed the effects of AZD6140 in clopidogrel-pretreated patients. Clopidogrel, in combination with aspirin, reduces cardiovascular events in patients with acute coronary syndromes (ACS). However, patients with poor inhibition of platelet aggregation with clopidogrel may be less well protected. AZD6140 is a reversible oral P2Y(12) receptor antagonist that has been studied in ACS patients in comparison with clopidogrel (DISPERSE-2 study). Patients were randomized to receive either AZD6140 90 mg twice a day, AZD6140 180 mg twice a day, or clopidogrel 75 mg once a day for up to 12 weeks in a double-blind, double-dummy design. One-half the patients allocated AZD6140 received a 270-mg loading dose. Patients randomized to receive clopidogrel were given a 300-mg loading dose unless they had already been treated with clopidogrel. Adenosine diphosphate-induced platelet aggregation was assessed by optical aggregometry on day 1 and at 4-week intervals. AZD6140 inhibited platelet aggregation in a dose-dependent fashion and both doses achieved greater levels of inhibition than clopidogrel (e.g., 4 weeks, 4-h postdose [mean (+/-SD)]: clopidogrel 64% [+/-22%], AZD6140 90 mg 79% [+/-22%], AZD6140 180 mg 95% [+/-8%]. AZD6140 also produced further suppression of platelet aggregation in patients previously treated with clopidogrel. AZD6140 exhibited greater mean inhibition of platelet aggregation than a standard regimen of clopidogrel in ACS patients. In addition, AZD6140 further suppressed platelet aggregation in clopidogrel pretreated patients.
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                Author and article information

                Journal
                Drug Des Devel Ther
                Drug Des Devel Ther
                Drug Design, Development and Therapy
                Drug Design, Development and Therapy
                Dove Medical Press
                1177-8881
                2019
                20 February 2019
                : 13
                : 719-730
                Affiliations
                [1 ]Department of Cardiology, Subei People’s Hospital of Jiangsu Province, Yangzhou University, Yangzhou, Jiangsu, China, yzhshys@ 123456163.com
                [2 ]Department of Geriatric Gastroenterology, First Affiliated Hospital, Nanjing Medical University, Nanjing, Jiangsu, China
                [3 ]Department of Cardiology, Nanjing First Hospital, Nanjing Heart Center, Nanjing Medical University, Nanjing, Jiangsu, China, tiannailiang@ 123456163.com
                Author notes
                Correspondence: Nai-Liang Tian, Department of Cardiology, Nanjing First Hospital, Nanjing Medical University, 68 Changle Road, Nanjing, Jiangsu 210006, China, Tel +86 25 5220 8048, Email tiannailiang@ 123456163.com
                Sheng-Hu He, Department of Cardiology, Subei People’s Hospital of Jiangsu Province, Yangzhou University, 98 Nantong West Road, Yangzhou, Jiangsu 225002, China, Tel +86 514 8737 3260, Email yzhshys@ 123456163.com
                Article
                dddt-13-719
                10.2147/DDDT.S196535
                6388955
                2f28bcea-5eb2-4e56-9d6c-1e6d8214c017
                © 2019 Fan et al. This work is published and licensed by Dove Medical Press Limited

                The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution - Non Commercial (unported, v3.0) License ( http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed.

                History
                Categories
                Original Research

                Pharmacology & Pharmaceutical medicine
                ticagrelor,clopidogrel,dual antiplatelet treatment,percutaneous coronary intervention,acute coronary syndrome

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