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      Differential Effects of Ticagrelor With or Without Aspirin on Platelet Reactivity and Coagulation Activation: A Randomized Trial in Healthy Volunteers

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          Abstract

          Dual antiplatelet therapy (DAPT) is standard in acute coronary heart disease but confers a bleeding risk. To compare the effects of ticagrelor‐monotherapy with ticagrelor‐based DAPT on hemostatic system activation, we conducted a randomized controlled trial in 44 volunteers using a loading‐dose regimen and measured platelet‐aggregometry triggered by adenosine diphosphate (multiple electrode aggregometry (MEA)‐ADP) and arachidonic acid (MEA‐AA), the vasodilator‐stimulated phosphoprotein (VASP), prothrombin fragment 1.2 (f1.2), and d‐Dimer. Ticagrelor‐based DAPT and ticagrelor‐monotherapy significantly decreased MEA‐ADP (Δmean: −51.4 (−56.9; −45.8) and −46.2 (−51.7; −40.7)) and VASP (Δmean: −70.3 (−76.2; −64.4) and −69.6 (−75.5; −63.7)) at 2 hours and over 24 hours. MEA‐AA was reduced significantly by both treatments (Δmean: −72.9 (−80.6; −65.3) and −25.7 (−33.3; −18.0)) at 2 hours, and stronger by ticagrelor‐based DAPT over 24 hours. Both treatments decreased f1.2 (geometric mean ratio (GMR): 0.92 (0.84; 1.01) and 0.88 (0.80; 0.96)) and d‐Dimer (GMR: 0.89 (0.86; 0.92) and 0.91 (0.88; 0.94)) at 2 hours and d‐Dimer over 24 hours. Ticagrelor‐monotherapy and ticagrelor‐based DAPT comparably affect hemostatic system activation.

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          Most cited references29

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          Cardiovascular disease in Europe 2014: epidemiological update.

          This paper provides an update for 2014 on the burden of cardiovascular disease (CVD), and in particular coronary heart disease (CHD) and stroke, across the countries of Europe. Cardiovascular disease causes more deaths among Europeans than any other condition, and in many countries still causes more than twice as many deaths as cancer. There is clear evidence in most countries with available data that mortality and case-fatality rates from CHD and stroke have decreased substantially over the last 5-10 years but at differing rates. The differing recent trends have therefore led to increasing inequalities in the burden of CVD between countries. For some Eastern European countries, including Russia and Ukraine, the mortality rate for CHD for 55-60 year olds is greater than the equivalent rate in France for people 20 years older.
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            2018 ESC/EACTS Guidelines on myocardial revascularization

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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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                Author and article information

                Contributors
                paul.kyrle@meduniwien.ac.at
                Journal
                Clin Pharmacol Ther
                Clin. Pharmacol. Ther
                10.1002/(ISSN)1532-6535
                CPT
                Clinical Pharmacology and Therapeutics
                John Wiley and Sons Inc. (Hoboken )
                0009-9236
                1532-6535
                28 September 2019
                February 2020
                28 September 2019
                : 107
                : 2 ( doiID: 10.1002/cpt.v107.2 )
                : 415-422
                Affiliations
                [ 1 ] Department of Medicine I Medical University of Vienna Vienna Austria
                [ 2 ] Center for Medical Statistics, Informatics and Intelligent Systems Medical University of Vienna Vienna Austria
                [ 3 ] Department of Medicine II Medical University of Vienna Vienna Austria
                [ 4 ] Landesapotheke Salzburg Salzburg Austria
                [ 5 ] Department of Clinical Pharmacology Medical University of Vienna Vienna Austria
                Author notes
                [*] [* ]Correspondence: Paul A. Kyrle ( paul.kyrle@ 123456meduniwien.ac.at )
                Author information
                https://orcid.org/0000-0003-2861-5771
                Article
                CPT1616
                10.1002/cpt.1616
                7006887
                31442298
                e108bc88-f0aa-4fe5-82fc-b658c5b0c331
                © 2019 The Authors. Clinical Pharmacology & Therapeutics published by Wiley Periodicals, Inc. on behalf of American Society for Clinical Pharmacology and Therapeutics.

                This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.

                History
                : 12 June 2019
                : 29 July 2019
                Page count
                Figures: 3, Tables: 2, Pages: 8, Words: 5829
                Funding
                Funded by: Medizinisch‐Wissenschaftlicher Fonds des Bürgermeisters der Bundeshauptstadt Wien
                Award ID: 12059
                Categories
                Article
                Research
                Articles
                Custom metadata
                2.0
                February 2020
                Converter:WILEY_ML3GV2_TO_JATSPMC version:5.7.5 mode:remove_FC converted:06.02.2020

                Pharmacology & Pharmaceutical medicine
                Pharmacology & Pharmaceutical medicine

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