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Evaluation of Time to Benefit of Statins for the Primary Prevention of Cardiovascular Events in Adults Aged 50 to 75 YearsA Meta-analysis

Educational Objective: To determine the time to benefit for prevention of a first major adverse cardiovascular event (MACE) in adults aged 50 to 75 years based on randomized clinical trials of statins.

1 Credit CME

JAMA Internal Medicine

Published Online: November 16, 2020

Original Investigation

Article Information and Disclosures

Lindsey C. Yourman, MD¹;

Irena S. Cenzer, MA²;

W. John Boscardin, PhD^2,3;

Brian T. Nguyen, BA^2,3,4;

Alexander K. Smith, MD, MPH^2,3;

Mara A. Schonberg, MD, MPH^5,6;

Nancy L. Schoenborn, MD, MHS⁷;

Eric W. Widera, MD^2,3;

Ariela Orkaby, MD, MPH^7,8,9;

Annette Rodriguez, MA^2,3,4;

Sei J. Lee, MD, MAS^2,3

Author Affiliations

¹Division of Geriatrics and Gerontology, School of Medicine, University of California, San Diego
²Geriatrics, Palliative and Extended Care Service Line, San Francisco VA (Veterans Affairs) Health Care System, San Francisco, California
³Division of Geriatrics, School of Medicine, University of California, San Francisco
⁴Northern California Institute for Research and Education, San Francisco
⁵Department of Medicine, Harvard Medical School, Cambridge, Massachusetts
⁶Department of General Medicine and Primary Care, Beth Israel Deaconess Medical Center, Boston, Massachusetts
⁷Division of Geriatric Medicine and Gerontology, School of Medicine, John Hopkins University, Baltimore, Maryland
⁸New England GRECC (Geriatrics Research, Education and Clinical Center), VA Boston Healthcare System, Boston, Massachusetts
⁹Division of Aging, Brigham & Women’s Hospital, Harvard Medical School, Boston, Massachusetts

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Key Points

Question What is the time to benefit of statin therapy for primary prevention of cardiovascular events in adults aged 50 to 75 years?

Findings In this survival meta-analysis of 8 trials randomizing 65 383 adults, 2.5 (95% CI, 1.7-3.4) years were needed to avoid 1 cardiovascular event for 100 patients treated with a statin.

Meaning These findings suggest that statin medications for the primary prevention of cardiovascular events may reduce cardiac events for some adults aged 50 to 75 years with a life expectancy of at least 2.5 years; no data suggest a mortality benefit.

Abstract

Importance Guidelines recommend targeting preventive interventions toward older adults whose life expectancy is greater than the intervention’s time to benefit (TTB). The TTB for statin therapy is unknown.

Objective To conduct a survival meta-analysis of randomized clinical trials of statins to determine the TTB for prevention of a first major adverse cardiovascular event (MACE) in adults aged 50 to 75 years.

Data Sources Studies were identified from previously published systematic reviews (Cochrane Database of Systematic Reviews and US Preventive Services Task Force) and a search of MEDLINE and Google Scholar for subsequently published studies until February 1, 2020.

Study Selection Randomized clinical trials of statins for primary prevention focusing on older adults (mean age >55 years).

Data Extraction and Synthesis Two authors independently abstracted survival data for the control and intervention groups. Weibull survival curves were fit, and a random-effects model was used to estimate pooled absolute risk reductions (ARRs) between control and intervention groups each year. Markov chain Monte Carlo methods were applied to determine time to ARR thresholds.

Main Outcomes and Measures The primary outcome was time to ARR thresholds (0.002, 0.005, and 0.010) for a first MACE, as defined by each trial. There were broad similarities in the definition of MACE across trials, with all trials including myocardial infarction and cardiovascular mortality.

Results Eight trials randomizing 65 383 adults (66.3% men) were identified. The mean age ranged from 55 to 69 years old and the mean length of follow-up ranged from 2 to 6 years. Only 1 of 8 studies showed that statins decreased all-cause mortality. The meta-analysis results suggested that 2.5 (95% CI, 1.7-3.4) years were needed to avoid 1 MACE for 100 patients treated with a statin. To prevent 1 MACE for 200 patients treated (ARR = 0.005), the TTB was 1.3 (95% CI, 1.0-1.7) years, whereas the TTB to avoid 1 MACE for 500 patients treated (ARR = 0.002) was 0.8 (95% CI, 0.5-1.0) years.

Conclusions and Relevance These findings suggest that treating 100 adults (aged 50-75 years) without known cardiovascular disease with a statin for 2.5 years prevented 1 MACE in 1 adult. Statins may help to prevent a first MACE in adults aged 50 to 75 years old if they have a life expectancy of at least 2.5 years. There is no evidence of a mortality benefit.

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Article Information

Accepted for Publication: September 6, 2020.

Published Online: November 16, 2020. doi:10.1001/jamainternmed.2020.6084

Corresponding Author: Lindsey C. Yourman, MD, Division of Geriatrics and Gerontology, School of Medicine, University of California, San Diego, 9500 Gilman Dr, MC 0665, Central Research Services Facility, Third Floor, Cubicle 331, La Jolla, CA 92107 (lyourman@health.ucsd.edu).

Author Contributions: Drs Yourman and Lee had full access to all the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis.

Concept and design: Yourman, Smith, Schonberg, Schoenborn, Widera, Rodriguez, Lee.

Acquisition, analysis, or interpretation of data: Yourman, Cenzer, Boscardin, Nguyen, Schoenborn, Orkaby, Rodriguez, Lee.

Drafting of the manuscript: Yourman, Schonberg, Rodriguez, Lee.

Critical revision of the manuscript for important intellectual content: Yourman, Cenzer, Boscardin, Nguyen, Smith, Schoenborn, Widera, Orkaby, Lee.

Statistical analysis: Cenzer, Boscardin, Rodriguez.

Obtained funding: Schonberg, Lee.

Administrative, technical, or material support: Yourman, Nguyen, Widera, Lee.

Supervision: Yourman, Smith, Lee.

Conflict of Interest Disclosures: Dr Yourman reported receiving grant 1TL1TR001443-01 from the National Institutes of Health (NIH) National Center for Advancing Translational Sciences during the conduct of the study. Dr Schonberg reported receiving grant R01CA181357 from the National Cancer Institute during the conduct of the study. Dr Schoenborn reported receiving grants from National Institute on Aging (NIA) outside the submitted work. Dr Orkaby reported receiving grants from the Department of Veterans Affairs (VA) and the NIA/NIH, during the conduct of the study. Dr Lee reported receiving grants from the NIH and VA Health Services Research and Development (HSR&D) during the conduct of the study. No other disclosures were reported.

Funding/Support: This project was supported by grants TL1TR001443, R01AG047897 and R01AG057751 from the NIH, grant IIR 15-434 from the VA HSR&D, and resources from the San Francisco VA Health Care System.

Role of the Funder/Sponsor: The funders had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.

AMA CME Accreditation Information

Credit Designation Statement: The American Medical Association designates this Journal-based CME activity activity for a maximum of 1.00  AMA PRA Category 1 Credit(s)™. Physicians should claim only the credit commensurate with the extent of their participation in the activity.

Successful completion of this CME activity, which includes participation in the evaluation component, enables the participant to earn up to:

1.00 Medical Knowledge MOC points in the American Board of Internal Medicine's (ABIM) Maintenance of Certification (MOC) program;;
1.00 Self-Assessment points in the American Board of Otolaryngology – Head and Neck Surgery’s (ABOHNS) Continuing Certification program;
1.00 MOC points in the American Board of Pediatrics’ (ABP) Maintenance of Certification (MOC) program;
1.00 Lifelong Learning points in the American Board of Pathology’s (ABPath) Continuing Certification program; and
1.00 credit toward the CME of the American Board of Surgery’s Continuous Certification program

It is the CME activity provider's responsibility to submit participant completion information to ACCME for the purpose of granting MOC credit.