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      Personalising the decision for prolonged dual antiplatelet therapy: development, validation and potential impact of prognostic models for cardiovascular events and bleeding in myocardial infarction survivors

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          Abstract

          Aims

          The aim of this study is to develop models to aid the decision to prolong dual antiplatelet therapy (DAPT) that requires balancing an individual patient’s potential benefits and harms.

          Methods and results

          Using population-based electronic health records (EHRs) (CALIBER, England, 2000–10), of patients evaluated 1 year after acute myocardial infarction (MI), we developed ( n = 12 694 patients) and validated ( n = 5613) prognostic models for cardiovascular (cardiovascular death, MI or stroke) events and three different bleeding endpoints. We applied trial effect estimates to determine potential benefits and harms of DAPT and the net clinical benefit of individuals. Prognostic models for cardiovascular events (c-index: 0.75 (95% CI: 0.74, 0.77)) and bleeding (c index 0.72 (95% CI: 0.67, 0.77)) were well calibrated: 3-year risk of cardiovascular events was 16.5% overall (5.2% in the lowest- and 46.7% in the highest-risk individuals), while for major bleeding, it was 1.7% (0.3% in the lowest- and 5.4% in the highest-risk patients). For every 10 000 patients treated per year, we estimated 249 (95% CI: 228, 269) cardiovascular events prevented and 134 (95% CI: 87, 181) major bleeding events caused in the highest-risk patients, and 28 (95% CI: 19, 37) cardiovascular events prevented and 9 (95% CI: 0, 20) major bleeding events caused in the lowest-risk patients. There was a net clinical benefit of prolonged DAPT in 63–99% patients depending on how benefits and harms were weighted.

          Conclusion

          Prognostic models for cardiovascular events and bleeding using population-based EHRs may help to personalise decisions for prolonged DAPT 1-year following acute MI.

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          Most cited references53

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          mice: Multivariate Imputation by Chained Equations inR

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            Refining clinical risk stratification for predicting stroke and thromboembolism in atrial fibrillation using a novel risk factor-based approach: the euro heart survey on atrial fibrillation.

            Contemporary clinical risk stratification schemata for predicting stroke and thromboembolism (TE) in patients with atrial fibrillation (AF) are largely derived from risk factors identified from trial cohorts. Thus, many potential risk factors have not been included. We refined the 2006 Birmingham/National Institute for Health and Clinical Excellence (NICE) stroke risk stratification schema into a risk factor-based approach by reclassifying and/or incorporating additional new risk factors where relevant. This schema was then compared with existing stroke risk stratification schema in a real-world cohort of patients with AF (n = 1,084) from the Euro Heart Survey for AF. Risk categorization differed widely between the different schemes compared. Patients classified as high risk ranged from 10.2% with the Framingham schema to 75.7% with the Birmingham 2009 schema. The classic CHADS(2) (Congestive heart failure, Hypertension, Age > 75, Diabetes, prior Stroke/transient ischemic attack) schema categorized the largest proportion (61.9%) into the intermediate-risk strata, whereas the Birmingham 2009 schema classified 15.1% into this category. The Birmingham 2009 schema classified only 9.2% as low risk, whereas the Framingham scheme categorized 48.3% as low risk. Calculated C-statistics suggested modest predictive value of all schema for TE. The Birmingham 2009 schema fared marginally better (C-statistic, 0.606) than CHADS(2). However, those classified as low risk by the Birmingham 2009 and NICE schema were truly low risk with no TE events recorded, whereas TE events occurred in 1.4% of low-risk CHADS(2) subjects. When expressed as a scoring system, the Birmingham 2009 schema (CHA(2)DS(2)-VASc acronym) showed an increase in TE rate with increasing scores (P value for trend = .003). Our novel, simple stroke risk stratification schema, based on a risk factor approach, provides some improvement in predictive value for TE over the CHADS(2) schema, with low event rates in low-risk subjects and the classification of only a small proportion of subjects into the intermediate-risk category. This schema could improve our approach to stroke risk stratification in patients with AF.
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              2015 ESC Guidelines for the management of acute coronary syndromes in patients presenting without persistent ST-segment elevation: Task Force for the Management of Acute Coronary Syndromes in Patients Presenting without Persistent ST-Segment Elevation of the European Society of Cardiology (ESC).

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                Author and article information

                Journal
                Eur Heart J
                Eur. Heart J
                eurheartj
                European Heart Journal
                Oxford University Press
                0195-668X
                1522-9645
                07 April 2017
                27 February 2017
                27 February 2017
                : 38
                : 14 , Focus Issue on Acute Coronary Syndrome
                : 1048-1055
                Affiliations
                [1 ]The Farr Institute of Health Informatics Research, University College London, London, UK
                [2 ]MRC Medical Bioinformatics Centre, Leeds Institute of Biomedical and Clinical Sciences, University of Leeds, UK
                [3 ]Centre for Cardiovascular Science, University of Edinburgh and Royal Infirmary of Edinburgh, Edinburgh, UK
                [4 ]Department of Medical Sciences Cardiology, Uppsala Clinical Research Centre, Uppsala University, Uppsala, Sweden
                [5 ]Department of Medical Statistics, London School of Hygiene and Tropical Medicine, London, UK
                [6 ]Bart’s Heart Centre, Barts and the London National Institute for Health Research Cardiovascular Biomedical Research Unit, London, UK
                Author notes
                [* ] Corresponding author. Tel: +44 20 3549 5329, Fax: +44 20 7813 0242, E-mail: h.hemingway@ 123456ucl.ac.uk

                See page 1056 for the editorial comment on this article (doi: [Related article:]10.1093/eurheartj/ehx127)

                Article
                ehw683
                10.1093/eurheartj/ehw683
                5400049
                28329300
                9dccd3de-d262-4525-a595-81ea67d46473
                © The Author 2017. Published on behalf of the European Society of Cardiology

                This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 02 June 2016
                : 23 September 2016
                : 30 December 2016
                Page count
                Pages: 9
                Funding
                Funded by: Medical Research Council Prognosis Research Strategy (PROGRESS) Partnership
                Award ID: G0902393/99558
                Funded by: Medical Research Council Population Health Scientist
                Award ID: MR/M015084/1
                Funded by: Farr Institute of Health Informatics Research, London, from the Medical Research Council, Arthritis Research UK, British Heart Foundation, Cancer Research UK, Chief Scientist Office, Economic and Social Research Council, Engineering and Physical Sciences Research Council, NIHR, National Institute for Social Care and Health Research, and Wellcome Trust (LP, S-CC, MP)
                Categories
                Clinical Research
                Thrombosis and Antithrombotic Therapy

                Cardiovascular Medicine
                prognosis,myocardial infarction,bleeding
                Cardiovascular Medicine
                prognosis, myocardial infarction, bleeding

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