Joseph C. Engeda, Stefan K. Lhachimi, Wayne D. Rosamond, Jennifer L. Lund, Thomas C. Keyserling, Monika M. Safford, Lisandro D. Colantonio, Paul Muntner, Christy L. Avery
Abstract
Background
Experimental and observational research has suggested the potential for increased type 2 diabetes (T2D) risk among populations taking statins for the primary prevention of atherosclerotic cardiovascular disease (ASCVD). However, few studies have directly compared statin-associated benefits and harms or examined heterogeneity by population subgroups or assumed treatment effect. Thus, we compared ASCVD risk reduction and T2D incidence increases across 3 statin treatment guidelines or recommendations among adults without a history of ASCVD or T2D who were eligible for statin treatment initiation.
Introduction
Statins are a widely prescribed class of lipid-lowering medication used to prevent atherosclerotic cardiovascular disease (ASCVD) [1, 2]. In 2013, the American College of Cardiology (ACC)/American Heart Association (AHA) updated previous cholesterol treatment guidelines, particularly with respect to ASCVD primary prevention [3]; these guidelines were further revised in 2018 [4]. Previous guidelines emphasized low-density lipoprotein cholesterol (LDL-C) levels for guiding statin treatment [5], while the 2013 ACC/AHA guidelines based statin treatment recommendations on predicted 10-year ASCVD risk. As a result, an estimated 10.4 million U.S. adults were newly eligible for statin treatment for the primary prevention of ASCVD, with adults 60–75 years of age versus other age groups being more likely to be newly eligible [6]. While not formal guidelines, other recommendations have the potential to further expand the population eligible for statin treatment for primary prevention of ASCVD, e.g., expanding guidelines to include populations with predicted 10-year risks of ASCVD of 5% or greater [7, 8].
Methods
Motivation for simulation model
This study has been performed according to the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) checklist and employed a simulation model to examine intended and unintended consequences of statin treatment guidelines or recommendations through synthesis of high-quality observational and experimental data [20]. A simulation model was conceptualized and then developed in September 2018 to evaluate statin guidelines and recommendations because few available studies (1) were contemporary, (2) spanned ages specified by current guidelines or recommendations, and (3) precisely and validly measured ASCVD and T2D incidence within generalizable male and female multi-ethnic populations with long-term follow-up [21]. This study did not consider costs associated with statins, T2D, or ASCVD.
Discussion
In this study, we examined the net effects of statins across 3 treatment guidelines or recommendations in a contemporary, biracial adult primary prevention population. We projected that 13 to 28 million non-Hispanic African American and white adults would be newly eligible for statin treatment, among whom one ASCVD event would be prevented for every 155–197 adults treated. Benefits of statin treatment were even more pronounced in males and older populations compared to females and younger populations. Quantifying harms associated with statin treatment was more complex, as changes in statin-associated T2D risk produced large differences in projected harms. Overall, these results suggest that further efforts are needed to better quantify statin-associated T2D risk across a range of populations, particularly female and younger adult populations for whom statin treatment may introduce a large relative burden of adverse events.
Acknowledgments
The authors thank the other investigators, the staff, and the participants of the REGARDS Study for the valuable contributions. A complete list of participating REGARDS investigators and institutions can be found at https://www.uab.edu/soph/regardsstudy/.
Citation: Engeda JC, Lhachimi SK, Rosamond WD, Lund JL, Keyserling TC, Safford MM, et al. (2020) Projections of incident atherosclerotic cardiovascular disease and incident type 2 diabetes across evolving statin treatment guidelines and recommendations: A modelling study. PLoS Med 17(8): e1003280. https://doi.org/10.1371/journal.pmed.1003280
Academic Editor: Leopold Aminde, Griffith University School of Medicine, AUSTRALIA
Received: November 11, 2019; Accepted: July 22, 2020; Published: August 26, 2020
This is an open access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.
Data Availability: NHANES data are available from https://www.cdc.gov/nchs/nhanes/index.htm. Data from REGARDS may only be accessible after submitting a proposal to the REGARDS study.
Funding: JCE T32HL007055 National Heart, Lung, and Blood Institute; T32AG049663 National Institute on Aging. The sponsor did not play any role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Competing interests: The authors have declared that no competing interests exist.
Abbreviations: ACC, American College of Cardiology; AHA, American Heart Association; ASCOT-LLA, Anglo-Scandinavian Cardiac Outcomes Trial-Lipid Lowering Arm; ASCVD, atherosclerotic cardiovascular disease; CCS, Canadian Cardiovascular Society; CHD, coronary heart disease; EAS, European Atherosclerosis Society; ESC, European Society of Cardiology; HR, hazard ratio; ICD-10, International Statistical Classification of Disease 10th edition; JUPITER, Justification for the Use of statins in Prevention: an Intervention Trial Evaluating Rosuvastatin; LDL-C, low-density lipoprotein cholesterol; LHH, likelihood to be helped or harmed; Lp(a), lipoprotein(a); NHANES, National Health and Nutrition Examination Survey; NICE, National Institute for Health and Care Excellence; NNH, number needed to harm; NNT, number needed to treat; PSA, probabilistic sensitivity analysis; RCT, randomized controlled trial; REGARDS, Reasons for Geographic and Racial Differences in Stroke; RR, relative risk; STROBE, Strengthening the Reporting of Observational Studies in Epidemiology; T2D, type 2 diabetes; USPSTF, U.S. Preventive Services Task Force.
