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Statin Use for the Primary Prevention of Cardiovascular Disease in AdultsUpdated Evidence Report and Systematic Review for the US Preventive Services Task Force

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1 Credit CME

Importance  A 2016 review for the US Preventive Services Task Force (USPSTF) found use of statins for primary prevention of cardiovascular disease (CVD) was associated with reduced mortality and cardiovascular outcomes.

Objective  To update the 2016 review on statins for primary prevention of CVD to inform the USPSTF

Data Sources  Ovid MEDLINE, Cochrane Central Register of Controlled Trials, and Cochrane Database of Systematic Reviews (to November 2021); surveillance through May 20, 2022.

Study Selection  Randomized clinical trials on statins vs placebo or no statin and statin intensity in adults without prior cardiovascular events; large cohort studies on harms.

Data Extraction and Synthesis  One investigator abstracted data; a second checked accuracy. Two investigators independently rated study quality.

Main Outcomes and Measures  All-cause and cardiovascular mortality, myocardial infarction, stroke, composite cardiovascular outcomes, and adverse events.

Results  Twenty-six studies were included: 22 trials (N = 90 624) with 6 months to 6 years of follow-up compared statins vs placebo or no statin, 1 trial (n = 5144) compared statin intensities, and 3 observational studies (n = 417 523) reported harms. Statins were significantly associated with decreased risk of all-cause mortality (risk ratio [RR], 0.92 [95% CI, 0.87 to 0.98]; absolute risk difference [ARD], −0.35% [95% CI, −0.57% to −0.14%]), stroke (RR, 0.78 [95% CI, 0.68 to 0.90]; ARD, −0.39% [95% CI, −0.54% to −0.25%]), myocardial infarction (RR, 0.67 [95% CI, 0.60 to 0.75]; ARD, −0.85% [95% CI, −1.22% to −0.47%]), and composite cardiovascular outcomes (RR, 0.72 [95% CI, 0.64 to 0.81]; ARD, −1.28% [95% CI, −1.61% to −0.95%]); the association with cardiovascular mortality was not statistically significant (RR, 0.91 [95% CI, 0.81 to 1.02]; ARD, −0.13%). Relative benefits were consistent in groups defined by demographic and clinical characteristics, although data for persons older than 75 years were sparse. Statin therapy was not significantly associated with increased risk of serious adverse events (RR, 0.97 [95% CI, 0.93 to 1.01]), myalgias (RR, 0.98 [95% CI, 0.86 to 1.11]), or elevated alanine aminotransferase level (RR, 0.94 [95% CI, 0.78 to 1.13]). Statin therapy was not significantly associated with increased diabetes risk overall (RR, 1.04 [95% CI, 0.92 to 1.19]), although 1 trial found high-intensity statin therapy was significantly associated with increased risk (RR, 1.25 [95% CI, 1.05 to 1.49]). Otherwise, there were no clear differences in outcomes based on statin intensity.

Conclusions and Relevance  In adults at increased CVD risk but without prior CVD events, statin therapy for primary prevention of CVD was associated with reduced risk of all-cause mortality and CVD events. Benefits of statin therapy appear to be present across diverse demographic and clinical populations, with consistent relative benefits in groups defined by demographic and clinical characteristics.

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Article Information

Corresponding Author: Roger Chou, MD, Pacific Northwest Evidence-based Practice Center, Oregon Health & Science University, 3181 SW Sam Jackson Park Rd, Mail Code BICC, Portland, OR 97239 (chour@ohsu.edu).

Accepted for Publication: June 29, 2022.

Author Contributions: Dr. Chou had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.

Concept and design: Chou, Dana, Ferencik.

Acquisition, analysis, or interpretation of data: Chou, Cantor, Dana, Wagner, Ahmed, Fu, Ferencik.

Drafting of the manuscript: Chou, Dana, Wagner, Ahmed, Fu, Ferencik.

Critical revision of the manuscript for important intellectual content: Chou, Cantor, Wagner, Ferencik.

Statistical analysis: Chou, Dana, Wagner, Fu.

Obtained funding: Chou, Cantor.

Administrative, technical, or material support: Cantor, Dana, Wagner.

Supervision: Chou.

Conflict of Interest Disclosures: Dr Ferencik reported receiving grants from the American Heart Association and serving as a consultant for Biograph Inc. No other disclosures were reported.

Funding/Support: This research was funded under contract HHSA290201500007i; Group A, Task Order 75Q80119F32009, from the Agency for Healthcare Research and Quality (AHRQ), US Department of Health and Human Services, under a contract to support the US Preventive Services Task Force (USPSTF).

Role of the Funder/Sponsor: Investigators worked with USPSTF members and AHRQ staff to develop the scope, analytic framework, and key questions for this review. AHRQ had no role in study selection, quality assessment, or synthesis. AHRQ staff provided project oversight, reviewed the report to ensure that the analysis met methodological standards, and distributed the draft for peer review. Otherwise, AHRQ had no role in the conduct of the study; collection, management, analysis, and interpretation of the data; and preparation, review, or approval of the manuscript findings. The opinions expressed in this document are those of the authors and do not reflect the official position of AHRQ or the US Department of Health and Human Services.

Additional Contributions: We thank the following individuals for their contributions to this project: Jennifer Lin, MD, MCR, Kaiser Permanente Evidence-based Practice Center, Portland, Oregon; Christina Bougatsos, MPH, Oregon Health & Science University, Portland; Yun Yu, MS, Oregon Health & Science University, Portland; Howard Tracer, MD, Agency for Healthcare Research and Quality; as well as the USPSTF. We also acknowledge past and current USPSTF members who contributed to topic deliberations. The USPSTF members, external reviewers, and federal partner reviewers did not receive financial compensation for their contributions.

Additional Information: A draft version of this evidence report underwent external peer review from 3 content experts (Jacquelyn Kulinski, MD, Medical College of Wisconsin, Milwaukee; Bruce Warden, PharmD, Oregon Health & Science University, Portland; Eugene Yang, MD, MS, University of Washington School of Medicine, Seattle); and 1 federal partner from the Centers for Disease Control and Prevention (CDC). Comments were presented to the USPSTF during its deliberation of the evidence and were considered in preparing the final evidence review.

Editorial Disclaimer: This evidence report is presented as a document in support of the accompanying USPSTF recommendation statement. It did not undergo additional peer review after submission to JAMA.

US Preventive Services Task Force. Final recommendation statement: statin use for the primary prevention of cardiovascular disease in adults: preventive medication. Updated November 13, 2022. Accessed June 25, 2022. https://www.uspreventiveservicestaskforce.org/uspstf/recommendation/statin-use-in-adults-preventive-medication
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Dormuth  CR , Filion  KB , Paterson  JM ,  et al; Canadian Network for Observational Drug Effect Studies Investigators.  Higher potency statins and the risk of new diabetes: multicentre, observational study of administrative databases.   BMJ. 2014;348:g3244. doi:10.1136/bmj.g3244PubMedGoogle ScholarCrossref
Mihaylova  B , Emberson  J , Blackwell  L ,  et al; Cholesterol Treatment Trialists’ (CTT) Collaborators.  The effects of lowering LDL cholesterol with statin therapy in people at low risk of vascular disease: meta-analysis of individual data from 27 randomised trials.   Lancet. 2012;380(9841):581-590. doi:10.1016/S0140-6736(12)60367-5PubMedGoogle ScholarCrossref
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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 CME points in the American Board of Surgery’s (ABS) Continuing Certification program

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

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