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      Cangrelor: Clinical Data, Contemporary Use, and Future Perspectives

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          Abstract

          Cangrelor is the only currently available intravenous platelet P2Y 12 receptor inhibitor. It is characterized by potent, predictable, and rapidly reversible antiplatelet effects. Cangrelor has been tested in the large CHAMPION (Cangrelor Versus Standard Therapy to Achieve Optimal Management of Platelet Inhibition) program, where it was compared with different clopidogrel regimens, and it is currently indicated for use in patients with coronary artery disease undergoing percutaneous coronary intervention. However, the uptake of cangrelor use varies across the globe and may also include patients with profiles different from those enrolled in the registration trials. These observations underscore the need to fully examine the safety and efficacy of cangrelor in postregistration studies. There are several ongoing and planned studies evaluating the use of cangrelor in real‐world practice which will provide important insights to this extent. The current article provides a review on the pharmacology, clinical studies, contemporary use of cangrelor in real‐world practice, a description of ongoing studies, and futuristic insights on potential strategies on how to improve outcomes of patients undergoing percutaneous coronary intervention.

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            Standardized bleeding definitions for cardiovascular clinical trials: a consensus report from the Bleeding Academic Research Consortium.

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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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                Author and article information

                Contributors
                leo.deluca@libero.it , ldeluca@scamilloforlanini.rm.it
                Journal
                J Am Heart Assoc
                J Am Heart Assoc
                10.1002/(ISSN)2047-9980
                JAH3
                ahaoa
                Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease
                John Wiley and Sons Inc. (Hoboken )
                2047-9980
                02 July 2021
                06 July 2021
                : 10
                : 13 ( doiID: 10.1002/jah3.v10.13 )
                : e022125
                Affiliations
                [ 1 ] Division of Cardiology Department of Cardiosciences Azienda Ospedaliera San Camillo‐Forlanini Roma Italy
                [ 2 ] FACT (French Alliance for Cardiovascular Trials) and INSERM U‐1148 AP‐HP Hôpital Bichat Université de Paris France
                [ 3 ] NHLI (National Heart and Lung Institute) Imperial College ICMS Royal Brompton Hospital London United Kingdom
                [ 4 ] Brigham and Women's Hospital Heart and Vascular Center Harvard Medical School Boston MA
                [ 5 ] Division of Cardiology A.O.U. Policlinico "G. Rodolico‐San Marco" University of Catania Catania Italy
                [ 6 ] Division of Cardiology University of Florida College of Medicine Jacksonville FL
                Author notes
                [*] [* ] Correspondence to: Leonardo De Luca, MD, PhD, Division of Cardiology, Department of Cardiosciences, Azienda Ospedaliera San Camillo‐Forlanini, Circonvallazione Gianicolense, 87, 00152 Roma, Italy. E‐mail: leo.deluca@ 123456libero.it ; ldeluca@ 123456scamilloforlanini.rm.it

                Author information
                https://orcid.org/0000-0002-8552-1272
                https://orcid.org/0000-0001-6896-2941
                https://orcid.org/0000-0002-1278-6245
                https://orcid.org/0000-0002-5156-7723
                https://orcid.org/0000-0001-8451-2131
                Article
                JAH36447
                10.1161/JAHA.121.022125
                8403274
                34212768
                f6e9ec92-2630-46cb-a71e-a855f25f6bb2
                © 2021 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.

                This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc-nd/4.0/ 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
                : 19 April 2021
                : 19 May 2021
                Page count
                Figures: 5, Tables: 1, Pages: 13, Words: 22077
                Categories
                Contemporary Review
                Contemporary Review
                Custom metadata
                2.0
                July 6, 2021
                Converter:WILEY_ML3GV2_TO_JATSPMC version:6.0.5 mode:remove_FC converted:16.08.2021

                Cardiovascular Medicine
                acute coronary syndromes,cangrelor,percutaneous coronary intervention,pharmacology,treatment

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