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      Optimal strategy of switching from clopidogrel to ticagrelor in Chinese acute coronary syndrome patients with complicated coronary artery disease: the switching from clopidogrel to ticagrelor (SHIFT-CACS) study

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          Abstract

          Supplemental Digital Content is available in the text

          Abstract

          Background:

          The dose and time point for switching from clopidogrel to ticagrelor remain controversial, especially for Chinese acute coronary syndrome (ACS) patients with complicated coronary artery disease (CAD). Hence, the purpose of this study was to further explore the optimal dose and time point for the switching strategy to balance the increase in platelet inhibition and the decrease in adverse events in Chinese ACS patients with complicated CAD managed by percutaneous coronary intervention (PCI).

          Methods:

          From July 2017 to December 2017, the prospective, randomized, open-label study (the SwitcHIng from clopidogrel to ticagrelor study) assigned the eligible Chinese ACS patients with complicated CAD managed by PCI ( n = 102) for 90 mg of ticagrelor at 12 h (T-90 mg-12 h), 90 mg of ticagrelor at 24 h (T-90 mg-24h) or 180 mg ticagrelor at 24 h (T-180 mg-24 h) after the last dose of clopidogrel. The primary endpoint was the comparison of maximal platelet aggregation (MPA) values at 2 h after switching strategies among the three groups. In addition, the MPA values at baseline, 8 h and before discharge and the rates of high on-treatment platelet reactivity were evaluated, the incidences of bleeding episodes and dyspnea during hospitalization and at 30-day follow-up in our study were also recorded. The MPA was measured by light transmittance aggregometry in our study. A repeated-measures analysis of variance (ANOVA) model and one-way ANOVA were used to compare data for the primary endpoint.

          Results:

          The MPA values were significantly decreased in the T-180 mg-24 h group compared with the T-90 mg-12 h group ( P = 0.017) and decreased numerically compared with the T-90 mg-24 h group ( P = 0.072) at 2 h. In particular, the MPA values were markedly reduced in the T-90 mg-24 h group compared with the T-90 mg-12 h group at 8 h after switching treatment ( P = 0.002). There was no significant difference among the three groups in all bleedings and dyspnea events.

          Conclusions:

          The optimal treatment strategy recommended in this study for Chinese ACS patients with complicated CAD managed by PCI is 180 or 90 mg of ticagrelor at 24 h after the last dose of clopidogrel. In addition, a negative interaction was detected in this study between the overlap for clopidogrel and ticagrelor at 12 h after the last dose of clopidogrel.

          Trial Registration:

          ClinicalTrials.gov, NCT03577652; http://clinicaltrials.gov/ct2/show/NCT03577652.

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          Most cited references38

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          The SYNTAX Score: an angiographic tool grading the complexity of coronary artery disease.

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            2018 ESC/EACTS Guidelines on myocardial revascularization

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              Thrombolysis in Myocardial Infarction (TIMI) Trial, Phase I: A comparison between intravenous tissue plasminogen activator and intravenous streptokinase. Clinical findings through hospital discharge.

              Intravenous administration of 80 mg of recombinant tissue plasminogen activator (rt-PA, 40, 20, and 20 mg in successive hours) and streptokinase (SK, 1.5 million units over 1 hr) was compared in a double-blind, randomized trial in 290 patients with evolving acute myocardial infarction. These patients entered the trial within 7 hr of the onset of symptoms and underwent baseline coronary arteriography before thrombolytic therapy was instituted. Ninety minutes after the start of thrombolytic therapy, occluded infarct-related arteries had opened in 62% of 113 patients in the rt-PA and 31% of 119 patients in the SK group (p less than .001). Twice as many occluded infarct-related arteries opened after rt-PA compared with SK at the time of each of seven angiograms obtained during the first 90 min after commencing thrombolytic therapy. Regardless of the time from onset of symptoms to treatment, more arteries were opened after rt-PA than SK. The reduction in circulating fibrinogen and plasminogen and the increase in circulating fibrin split products at 3 and 24 hr were significantly less in patients treated with rt-PA than in those treated with SK (p less than .001). The occurrence of bleeding events, administration of blood transfusions, and reocclusion of the infarct-related artery was comparable in the two groups. Thus, in patients with acute myocardial infarction, rt-PA elicited reperfusion in twice as many occluded infarct-related arteries as compared with SK at each of seven serial observations during the first 90 min after onset of treatment.
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                Author and article information

                Journal
                Chin Med J (Engl)
                Chin. Med. J
                CM9
                Chinese Medical Journal
                Wolters Kluwer Health
                0366-6999
                2542-5641
                5 October 2019
                23 September 2019
                : 132
                : 19
                : 2292-2299
                Affiliations
                [1 ]Department of Cardiology, Institute of Cardiovascular Research, General Hospital of Northern Theater Command, Shenyang, Liaoning 110840, China
                [2 ]Department of Clinical Pharmacy, Shenyang Pharmaceutical University, Shenyang, Liaoning 110016, China.
                Author notes
                Correspondence to: Dr. Xiao-Zeng Wang, Department of Cardiology, Institute of Cardiovascular Research, General Hospital of Northern Theater Command, No. 83 Wenhua Road, Shenyang, Liaoning 110840, China E-Mail: wxiaozeng@ 123456163.com
                Article
                CMJ-2019-745
                10.1097/CM9.0000000000000444
                6819042
                31567375
                f8b22f4e-5ef5-428e-b6b4-aae9abb5d9b4
                Copyright © 2019 The Chinese Medical Association, produced by Wolters Kluwer, Inc. under the CC-BY-NC-ND license.

                This is an open access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal. http://creativecommons.org/licenses/by-nc-nd/4.0

                History
                : 27 May 2019
                Categories
                Original Articles
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                clopidogrel,drug substitution,pharmacology,ticagrelor
                clopidogrel, drug substitution, pharmacology, ticagrelor

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