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      Statins and new-onset atrial fibrillation in a cohort of patients with hypertension. Analysis of electronic health records, 2006–2015

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          Abstract

          Hypertension is the most prevalent risk factor for new-onset atrial fibrillation (AF). But few studies have addressed the effect of statins on the incidence of this arrhythmia in patients with hypertension. This study aimed to evaluate the effect of statins on new-onset of this arrhythmia in a hypertensive population, accounting for AF risk. Data from the Information System for the Development of Research in Primary Care was used to recruit a retrospective cohort of ≥55-year-old hypertensive individuals with no ischemic vascular disease, in 2006–2007, followed up through 2015. The effect of initiating statin treatment on new-onset atrial fibrillation was assessed with Cox proportional hazards models adjusted by the propensity score of receiving statin treatment, in the overall study population and stratified by AF risk. Of 100 276 included participants, 9814 initiated statin treatment. The AF incidence per 1000 person-years (95% confidence interval) was 12.5 (12.3–12.8). Statin use associated with a significant (9%) reduction in AF incidence. Differences in absolute AF incidence were higher in the highest AF risk subgroup, and the estimated number needed to treat to avoid one case was 720. The relative effect was poor, similar across groups, and non-significant, as was the association of statins with adverse effects. We found a limited protective effect of statins over new-onset AF in this hypertensive population with no ischemic vascular disease. If there is no further indication, hypertensive patients would not benefit from statin use solely for AF primary prevention.

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          Prevalence of diagnosed atrial fibrillation in adults: national implications for rhythm management and stroke prevention: the AnTicoagulation and Risk Factors in Atrial Fibrillation (ATRIA) Study.

          Atrial fibrillation is the most common arrhythmia in elderly persons and a potent risk factor for stroke. However, recent prevalence and projected future numbers of persons with atrial fibrillation are not well described. To estimate prevalence of atrial fibrillation and US national projections of the numbers of persons with atrial fibrillation through the year 2050. Cross-sectional study of adults aged 20 years or older who were enrolled in a large health maintenance organization in California and who had atrial fibrillation diagnosed between July 1, 1996, and December 31, 1997. Prevalence of atrial fibrillation in the study population of 1.89 million; projected number of persons in the United States with atrial fibrillation between 1995-2050. A total of 17 974 adults with diagnosed atrial fibrillation were identified during the study period; 45% were aged 75 years or older. The prevalence of atrial fibrillation was 0.95% (95% confidence interval, 0.94%-0.96%). Atrial fibrillation was more common in men than in women (1.1% vs 0.8%; P<.001). Prevalence increased from 0.1% among adults younger than 55 years to 9.0% in persons aged 80 years or older. Among persons aged 50 years or older, prevalence of atrial fibrillation was higher in whites than in blacks (2.2% vs 1.5%; P<.001). We estimate approximately 2.3 million US adults currently have atrial fibrillation. We project that this will increase to more than 5.6 million (lower bound, 5.0; upper bound, 6.3) by the year 2050, with more than 50% of affected individuals aged 80 years or older. Our study confirms that atrial fibrillation is common among older adults and provides a contemporary basis for estimates of prevalence in the United States. The number of patients with atrial fibrillation is likely to increase 2.5-fold during the next 50 years, reflecting the growing proportion of elderly individuals. Coordinated efforts are needed to face the increasing challenge of optimal stroke prevention and rhythm management in patients with atrial fibrillation.
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            Survival bias associated with time-to-treatment initiation in drug effectiveness evaluation: a comparison of methods.

            The authors compared five methods of studying survival bias associated with time-to-treatment initiation in a drug effectiveness study using medical administrative databases (1996-2002) from Quebec, Canada. The first two methods illustrated how survival bias could be introduced. Three additional methods were considered to control for this bias. Methods were compared in the context of evaluating statins for secondary prevention in elderly patients post-acute myocardial infarction who initiated statins within 90 days after discharge and those who did not. Method 1 that classified patients into users and nonusers at discharge resulted in an overestimation of the benefit (38% relative risk reduction at 1 year). In method 2, following users from the time of the first prescription and nonusers from a randomly selected time between 0 and 90 days attenuated the effect toward the null (10% relative risk reduction). Method 3 controlled for survival bias by following patients from the end of the 90-day time window; however, it suffered a major loss of statistical efficiency and precision. Method 4 matched prescription time distribution between users and nonusers at cohort entry. Method 5 used a time-dependent variable for treatment initiation. Methods 4 and 5 better controlled for survival bias and yielded similar results, suggesting a 20% risk reduction of recurrent myocardial infarction or death events.
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              Impact of atrial fibrillation on mortality, stroke, and medical costs.

              The impact of atrial fibrillation (AF) on mortality, stroke, and medical costs is unknown. We conducted a prospective cohort study of hospitalized Medicare patients with AF and 1 other cardiovascular diagnosis (CVD) compared with a matched group without AF (n = 26,753), randomly selected in 6 age-sex strata from 1989 MedPAR files of more than 1 million patients diagnosed as having AF. Stroke rates were also determined in another cohort free of CVD (n = 14,267). Total medical costs after hospitalization were available from a 1991 cohort. Cumulative mortality, stroke rates, and costs following index admission were adjusted by multivariate and proportional hazard regression analyses. Mortality rates were high in individuals with CVD, ranging from 19.0% to 52.1% in 1 year. Adjusted relative mortality risk was approximately 20% higher in patients with AF in all age-sex strata during each of the 3 years studied (P < .05). Incidence of stroke was high in individuals with CVD, 6.2% to 15.4% in 1 year, with and without AF, and was at least 5-fold higher than in individuals without CVD. In those with CVD, stroke rates were approximately 25% higher in women with AF (P < .05) but only 10% higher in men. Adjusted total Medicare spending in 1 year was 8.6- to 22.6-fold greater in men, and 9.8- to 11.2-fold greater in women with AF (P < .05). Second- and third-year costs were increased as well. Prevention of AF and treatment of patients with AF and associated CVD may yield benefits in reduced mortality and stroke as well as reducing health care costs.
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                Author and article information

                Contributors
                Role: ConceptualizationRole: InvestigationRole: MethodologyRole: Project administrationRole: ValidationRole: Writing – original draft
                Role: ConceptualizationRole: InvestigationRole: MethodologyRole: SupervisionRole: ValidationRole: Writing – review & editing
                Role: Data curationRole: Formal analysisRole: InvestigationRole: MethodologyRole: SoftwareRole: Visualization
                Role: InvestigationRole: MethodologyRole: VisualizationRole: Writing – review & editing
                Role: Funding acquisitionRole: InvestigationRole: ResourcesRole: ValidationRole: Writing – review & editing
                Role: ConceptualizationRole: InvestigationRole: ValidationRole: Writing – review & editing
                Role: Data curationRole: MethodologyRole: SoftwareRole: Validation
                Role: InvestigationRole: MethodologyRole: VisualizationRole: Writing – review & editing
                Role: ConceptualizationRole: Funding acquisitionRole: InvestigationRole: Project administrationRole: ResourcesRole: Supervision
                Role: Editor
                Journal
                PLoS One
                PLoS ONE
                plos
                plosone
                PLoS ONE
                Public Library of Science (San Francisco, CA USA )
                1932-6203
                26 October 2017
                2017
                : 12
                : 10
                : e0186972
                Affiliations
                [1 ] Vascular Health Research Group of Girona (ISV-Girona). Institut Universitari d’Investigació en Atenció Primària Jordi Gol (IDIAP Jordi Gol), Girona, Catalonia, Spain
                [2 ] Institut d’Investigació Biomèdica de Girona (IDIBGI), Dr. Josep Trueta University Hospital, Girona, Catalonia, Spain
                [3 ] Translab Research Group. Department of Medical Sciences, School of Medicine, University of Girona, Girona, Catalonia, Spain
                [4 ] Primary Care Services, Girona. Catalan Institute of Health (ICS), Girona, Catalonia, Spain
                University of British Columbia, CANADA
                Author notes

                Competing Interests: M.G.G. and R.R. collaborated (without receiving any personal fee) in 2 projects of primary care for the institute IDIAP Jordi Gol funded by AstraZeneca and AMGEN that are unrelated to the present work. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

                Author information
                http://orcid.org/0000-0001-7970-5537
                Article
                PONE-D-17-22148
                10.1371/journal.pone.0186972
                5658105
                29073212
                61d1a0cc-1ee3-4d74-a598-df6e0d00fe97
                © 2017 Alves-Cabratosa et al

                This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                : 20 June 2017
                : 11 October 2017
                Page count
                Figures: 1, Tables: 2, Pages: 13
                Funding
                Funded by: IDIAP Jordi Gol and Primary Care Services
                Award ID: 4R14/026
                Funded by: funder-id http://dx.doi.org/10.13039/501100004587, Instituto de Salud Carlos III;
                Award ID: RedIAPP RD16/0007/0004
                Lia Alves-Cabratosa was supported by a Ph.D. grant from Institut d’Investigació en Atenció Primària Jordi Gol (IDIAP Jordi Gol) and Primary Care Services (4R14/026). This project was also supported by clinical research grants from Carlos III Health Institute, within the Net for Research in Preventive Activities and Health Enhancement (RedIAPP RD16/0007/0004) framework; the Spanish Ministry of Health(EC10-84); and the Agency for Management of University and Research Grants (2014 SGR 902).
                Categories
                Research Article
                Medicine and Health Sciences
                Pharmacology
                Drugs
                Statins
                Medicine and Health Sciences
                Cardiology
                Arrhythmia
                Atrial Fibrillation
                Medicine and Health Sciences
                Cardiology
                Arrhythmia
                Medicine and Health Sciences
                Vascular Medicine
                Blood Pressure
                Hypertension
                Medicine and Health Sciences
                Endocrinology
                Endocrine Disorders
                Diabetes Mellitus
                Medicine and Health Sciences
                Metabolic Disorders
                Diabetes Mellitus
                Medicine and Health Sciences
                Vascular Medicine
                Coronary Heart Disease
                Medicine and Health Sciences
                Cardiology
                Coronary Heart Disease
                Research and Analysis Methods
                Research Design
                Clinical Research Design
                Adverse Events
                Medicine and Health Sciences
                Pharmaceutics
                Drug Therapy
                Custom metadata
                All relevant data are within the paper. Personal health data underlying the findings of our study are not publicly available due to legal reasons related to data privacy protection; the data contains identifying human information and are unsuitable for public deposition. Information on how to submit an application for gaining access to SIDIAP data is available at http://www.sidiap.org/index.php?lang=en. To request access to the analyses scripts, please contact the corresponding author, Dr. Rafel Ramos at rramos.girona.ics@ 123456gencat.cat .

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