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      Safety and Efficacy of Ticagrelor versus Clopidogrel in East Asian Patients with Acute Coronary Syndrome Undergoing Percutaneous Coronary Intervention Treated with Dual Antiplatelet Therapy: A Meta-Analysis of Randomized Controlled Trials

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          Abstract

          Introduction

          The treatment strategy for dual antiplatelet therapy (DAPT) with ticagrelor has been controversial in East Asian patients with acute coronary syndrome (ACS) undergoing percutaneous coronary intervention (PCI). Our meta-analysis aimed to demonstrate whether intensified antithrombotic regimens with ticagrelor plus aspirin have more beneficial effects and fewer adverse events compared to those of clopidogrel plus aspirin in East Asian patients with ACS undergoing PCI.

          Methods

          We searched PubMed, Embase, Web of Science, ScienceDirect, Clinical Trials, Cochrane Library, and Chinese Clinical Trial Registry for randomized controlled trials (RCTs) comparing the efficacy of DAPT with ticagrelor or clopidogrel plus aspirin for secondary prevention of ACS in East Asian patients undergoing PCI. Risk ratios (RRs) and 95% confidence intervals (CIs) were used as the metrics of choice for assessing treatment effects. The primary endpoint was bleeding events, and the secondary endpoints were major adverse cardiovascular and cerebrovascular events (MACCEs, including cardiovascular death, nonfatal myocardial infarction [MI], and stroke), all-cause death, and definite/probable/possible stent thrombosis. The I 2 index was used to assess heterogeneity.

          Results

          Six RCTs involving a total of 2,725 patients met the inclusion criteria. The incidence of all bleeding events with ticagrelor was higher than that with clopidogrel (RR, 1.65; 95% CI, 1.31–2.07), but the incidence of MACCE was not significantly different between the two groups (RR, 1.08; 95% CI, 0.54–2.16). All-cause death (RR, 1.10; 95% CI, 0.67–1.79), cardiovascular death (RR, 1.42; 95% CI, 0.68–2.98), nonfatal MI (RR, 0.92; 95% CI, 0.48–1.78), stroke (RR, 1.00; 95% CI, 0.40–2.50), and stent thrombosis (RR, 0.76; 95% CI, 0.19–2.98) were not statistically different between the two groups.

          Conclusion

          Ticagrelor increased the risk of bleeding and did not increase treatment efficacy compared to that of clopidogrel in the East Asian population who have ACS treated with PCI.

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          Most cited references38

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          Ticagrelor versus clopidogrel in patients with acute coronary syndromes.

          Ticagrelor is an oral, reversible, direct-acting inhibitor of the adenosine diphosphate receptor P2Y12 that has a more rapid onset and more pronounced platelet inhibition than clopidogrel. In this multicenter, double-blind, randomized trial, we compared ticagrelor (180-mg loading dose, 90 mg twice daily thereafter) and clopidogrel (300-to-600-mg loading dose, 75 mg daily thereafter) for the prevention of cardiovascular events in 18,624 patients admitted to the hospital with an acute coronary syndrome, with or without ST-segment elevation. At 12 months, the primary end point--a composite of death from vascular causes, myocardial infarction, or stroke--had occurred in 9.8% of patients receiving ticagrelor as compared with 11.7% of those receiving clopidogrel (hazard ratio, 0.84; 95% confidence interval [CI], 0.77 to 0.92; P<0.001). Predefined hierarchical testing of secondary end points showed significant differences in the rates of other composite end points, as well as myocardial infarction alone (5.8% in the ticagrelor group vs. 6.9% in the clopidogrel group, P=0.005) and death from vascular causes (4.0% vs. 5.1%, P=0.001) but not stroke alone (1.5% vs. 1.3%, P=0.22). The rate of death from any cause was also reduced with ticagrelor (4.5%, vs. 5.9% with clopidogrel; P<0.001). No significant difference in the rates of major bleeding was found between the ticagrelor and clopidogrel groups (11.6% and 11.2%, respectively; P=0.43), but ticagrelor was associated with a higher rate of major bleeding not related to coronary-artery bypass grafting (4.5% vs. 3.8%, P=0.03), including more instances of fatal intracranial bleeding and fewer of fatal bleeding of other types. In patients who have an acute coronary syndrome with or without ST-segment elevation, treatment with ticagrelor as compared with clopidogrel significantly reduced the rate of death from vascular causes, myocardial infarction, or stroke without an increase in the rate of overall major bleeding but with an increase in the rate of non-procedure-related bleeding. (ClinicalTrials.gov number, NCT00391872.) 2009 Massachusetts Medical Society
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            Ticagrelor plus aspirin for 1 month, followed by ticagrelor monotherapy for 23 months vs aspirin plus clopidogrel or ticagrelor for 12 months, followed by aspirin monotherapy for 12 months after implantation of a drug-eluting stent: a multicentre, open-label, randomised superiority trial

            We hypothesised that ticagrelor, in combination with aspirin for 1 month, followed by ticagrelor alone, improves outcomes after percutaneous coronary intervention compared with standard antiplatelet regimens.
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              Effect of P2Y12 Inhibitor Monotherapy vs Dual Antiplatelet Therapy on Cardiovascular Events in Patients Undergoing Percutaneous Coronary Intervention

              Data on P2Y12 inhibitor monotherapy after short-duration dual antiplatelet therapy (DAPT) in patients undergoing percutaneous coronary intervention are limited.
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                Author and article information

                Journal
                Cardiology
                Cardiology
                CRD
                CRD
                Cardiology
                S. Karger AG (Basel, Switzerland )
                0008-6312
                1421-9751
                24 April 2023
                August 2023
                : 148
                : 4
                : 363-373
                Affiliations
                [a ]College of Life Science and Biopharmaceutical, Shenyang Pharmaceutical University, Shenyang, China
                [b ]Department of Cardiology, General Hospital of Northern Theater Command, Shenyang, China
                Author notes
                Correspondence to: Xiaozeng Wang, wxiaozeng@ 123456163.com
                Article
                530602
                10.1159/000530602
                10614237
                37094558
                0ba14259-38f2-4be4-99f0-1e0c06496ce9
                © 2023 The Author(s). Published by S. Karger AG, Basel

                This article is licensed under the Creative Commons Attribution 4.0 International License (CC BY) ( http://www.karger.com/Services/OpenAccessLicense). Usage, derivative works and distribution are permitted provided that proper credit is given to the author and the original publisher.

                History
                : 6 January 2023
                : 3 April 2023
                : 2023
                Page count
                Figures: 3, Tables: 3, References: 38, Pages: 11
                Funding
                This research was funded by the China National Key R&D Project (No. SQ2022YFC2500062), project title: coronary heart disease (CHD) individualized precision diagnosis system building and optimization strategy research for coronary heart disease.
                Categories
                Thrombocardiology: Systematic Review

                acute coronary syndrome,ticagrelor,clopidogrel,dual antiplatelet therapy,percutaneous coronary intervention

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