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      β blockers and mortality after myocardial infarction in patients without heart failure: multicentre prospective cohort study

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          Abstract

          Objective To assess the association between early and prolonged β blocker treatment and mortality after acute myocardial infarction.

          Design Multicentre prospective cohort study.

          Setting Nationwide French registry of Acute ST- and non-ST-elevation Myocardial Infarction (FAST-MI) (at 223 centres) at the end of 2005.

          Participants 2679 consecutive patients with acute myocardial infarction and without heart failure or left ventricular dysfunction.

          Main outcome measures Mortality was assessed at 30 days in relation to early use of β blockers (≤48 hours of admission), at one year in relation to discharge prescription, and at five years in relation to one year use.

          Results β blockers were used early in 77% (2050/2679) of patients, were prescribed at discharge in 80% (1783/2217), and were still being used in 89% (1230/1383) of those alive at one year. Thirty day mortality was lower in patients taking early β blockers (adjusted hazard ratio 0.46, 95% confidence interval 0.26 to 0.82), whereas the hazard ratio for one year mortality associated with β blockers at discharge was 0.77 (0.46 to 1.30). Persistence of β blockers at one year was not associated with lower five year mortality (hazard ratio 1.19, 0.65 to 2.18). In contrast, five year mortality was lower in patients continuing statins at one year (hazard ratio 0.42, 0.25 to 0.72) compared with those discontinuing statins. Propensity score and sensitivity analyses showed consistent results.

          Conclusions Early β blocker use was associated with reduced 30 day mortality in patients with acute myocardial infarction, and discontinuation of β blockers at one year was not associated with higher five year mortality. These findings question the utility of prolonged β blocker treatment after acute myocardial infarction in patients without heart failure or left ventricular dysfunction.

          Trial registration Clinical trials NCT00673036.

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          Most cited references18

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          2013 ACCF/AHA guideline for the management of ST-elevation myocardial infarction: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines.

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            Relationship between adherence to evidence-based pharmacotherapy and long-term mortality after acute myocardial infarction.

            The extent to which drug adherence may affect survival remains unclear, in part because mortality differences may be attributable to "healthy adherer" behavioral attributes more so than to pharmacological benefits. To explore the relationship between drug adherence and mortality in survivors of acute myocardial infarction (AMI). Population-based, observational, longitudinal study of 31 455 elderly AMI survivors between 1999 and 2003 in Ontario. All patients filled a prescription for statins, beta-blockers, or calcium channel blockers, with the latter drug considered a control given the absence of clinical trial-proven survival benefits. Patient adherence was subdivided a priori into 3 categories--high (proportion of days covered, > or =80%), intermediate (proportion of days covered, 40%-79%), and low (proportion of days covered, <40%)--and compared with long-term mortality (median of 2.4 years of follow-up) using multivariable survival models (and propensity analyses) adjusted for sociodemographic factors, illness severity, comorbidities, and concomitant use of evidence-based therapies. Among statin users, compared with their high-adherence counterparts, the risk of mortality was greatest for low adherers (deaths in 261/1071 (24%) vs 2310/14,345 (16%); adjusted hazard ratio, 1.25; 95% confidence interval, 1.09-1.42; P = .001) and was intermediary for intermediate adherers (deaths in 472/2407 (20%); adjusted hazard ratio, 1.12; 95% confidence interval, 1.01-1.25; P = .03). A similar but less pronounced dose-response-type adherence-mortality association was observed for beta-blockers. Mortality was not associated with adherence to calcium channel blockers. Moreover, sensitivity analyses demonstrated no relationships between drug adherence and cancer-related admissions, outcomes for which biological plausibility do not exist. The long-term survival advantages associated with improved drug adherence after AMI appear to be class-specific, suggesting that adherence outcome benefits are mediated by drug effects and do not merely reflect an epiphenomenon of "healthy adherer" behavioral attributes.
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              CIRCULATION

              SS Chugh (1964)
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                Author and article information

                Contributors
                Role: associate professor of cardiology
                Role: clinical cardiologist
                Role: associate professor of cardiology
                Role: associate professor of allergology
                Role: associate professor of cardiology
                Role: professor of cardiology
                Role: professor of cardiology
                Role: clinical cardiologist
                Role: professor of cardiology
                Role: clinical cardiologist
                Role: clinical cardiologist
                Role: professor of cardiology
                Role: professor of cardiology
                Role: professor of cardiology
                Role: professor of cardiology
                Role: professor of pharmacology
                Role: professor of cardiology
                Journal
                BMJ
                BMJ
                bmj
                The BMJ
                BMJ Publishing Group Ltd.
                0959-8138
                1756-1833
                2016
                20 September 2016
                : 354
                : i4801
                Affiliations
                [1 ]Department of Cardiology, Hôpital Européen Georges Pompidou, 75015 Paris, France
                [2 ]Assistance Publique-Hôpitaux de Paris, Paris, France
                [3 ]Université Paris-Descartes, Paris, France
                [4 ]Department of Critical Care, Hôpital Européen Georges Pompidou, Paris, France
                [5 ]Department of Dermatology and Allergology, Tenon Hospital, Paris, France
                [6 ]Sorbonne University, Université Pierre et Marie Curie (UPMC-Paris 06), Paris, France
                [7 ]INSERM U1135-CIMI, Paris, France
                [8 ]Hôpital Bichat, Paris, France
                [9 ]Université Paris Diderot, Paris, France
                [10 ]INSERM U 698, Paris, France
                [11 ]Hôpital cardiologique du Haut Levêque, Pessac, France
                [12 ]Université Bordeaux Segalen, Bordeaux, France
                [13 ]Hôpital du Bocage, Dijon, France
                [14 ]Université de Bourgogne, Dijon, France
                [15 ]Hôpital St Joseph et St Luc, Lyon, France
                [16 ]Hôpital cardiologique Louis Pradel, Lyon, France
                [17 ]Université Lyon 1, Lyon, France
                [18 ]Clinique St Gatien, Tours, France
                [19 ]Groupe Hospitalier Intercommunal Le Raincy-Montfermeil, Montfermeil, France
                [20 ]Hôpital Jean Minjoz, Besançon, France
                [21 ]Université de Franche Comté, Besançon, France
                [22 ]Department of Cardiology B and Epidemiology, Toulouse University Hospital, Toulouse, France
                [23 ]UMR INSERM 1027, Toulouse, France
                [24 ]Institut Lorrain du Cœur et des Vaisseaux
                [25 ]Université de Lorraine, Nancy, France
                [26 ]Hôpital Saint Antoine, Department of Clinical Pharmacology and Unité de Recherche Clinique (URCEST), Paris, France
                [27 ]Université Pierre et Marie Curie (UPMC-Paris 06), Paris, France
                [28 ]INSERM U-698, Paris, France
                [29]Contributors: ND and TS planned and designed the study; they contributed equally to the work. EP, ND, and TS were responsible for data management and analysis. EP, ER, ND, and TS drafted the manuscript. All authors revised the paper critically for important intellectual content and approved the final version of the manuscript. ND supervised the study and is the guarantor.
                Author notes
                Correspondence to: E Puymirat etienne.puymirat@ 123456egp.aphp.fr
                Article
                puye033671
                10.1136/bmj.i4801
                5029148
                27650822
                95800a6b-7337-4dbe-84f1-24891b87b4c6
                Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions

                This is an Open Access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 3.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/3.0/.

                History
                : 02 September 2016
                Categories
                Research

                Medicine
                Medicine

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