Evaluation of Time to Benefit of Statins for the Primary Prevention of Cardiovascular Events in Adults Aged 50 to 75 Years: A Meta-analysis
Open accessAbstract
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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A meta-analysis of statin trials showed that the time to benefit is 2.5 years.
“For statins, a meta-analysis of the previously mentioned trials showed that the time to benefit is 2.5 years (75).”
From 13. Older Adults: Standards of Care in Diabetes—2025 (2025) · cites this paper as [75]
The Key Points and Discussion report a 2.5-year time to benefit, but specifically for preventing one major adverse cardiovascular event per 100 adults aged 50–75 treated with statins for primary prevention. The citing sentence presents 2.5 years as a general time to benefit for statins without that outcome, treatment threshold, or population. (LLM, conf=0.84)
Experimental — accuracy not yet measuredThe time to benefit for statins is 2.5 years.
“a more specific concept is the time to benefit for a therapy, which, for statins, is 2.5 years”
From 13. Older Adults: Standards of Care in Diabetes—2026 (2026) · cites this paper as [83]
The Results report a 2.5-year time to benefit, but specifically for preventing one major adverse cardiovascular event per 100 adults aged 50–75 treated with a statin. The paper studies primary prevention; the citing sentence presents 2.5 years as the time to benefit for statins generally, without the population or benefit threshold that determines the estimate. (LLM, conf=0.88)
Experimental — accuracy not yet measuredFor statins, a meta-analysis of clinical trials showed that the time to benefit is 2.5 years.
“For statins, a meta-analysis of the previously mentioned trials showed that the time to benefit is 2.5 years (73).”
From 13. Older Adults: <i>Standards of Care in Diabetes—2024</i> (2024) · cites this paper as [73]
People with an eGFR below 45 mL/min/1.73 m2 who are not dialysis-dependent are at very high to extremely high risk for ASCVD events.
“Persons with eGFR <45 mL/min/1.73 m2 who are not dialysis-dependent are at very high to extremely high risk for ASCVD events and should be treated to achieve LDL-C, non-HDL-C, and apo B goals with a statin and ezetimibe,357 because higher doses of statins alone have not been proven to be safe in the setting of CKD.”
From American Association of Clinical Endocrinology Clinical Practice Guideline: Developing a Diabetes Mellitus Comprehensive Care Plan-2022 Update. (2022) · cites this paper as [357]
The Results and Conclusions discuss statins for primary prevention in adults aged 50–75, but do not classify ASCVD risk by kidney function. Searches for eGFR below 45, dialysis dependence, and chronic kidney disease found no passage addressing the claimed risk category. (LLM, conf=0.77)
Experimental — accuracy not yet measuredStatin benefit for CVD is not evident in dialysis-dependent persons.
“However, the beneficial effect of statins is not apparent in persons who require dialysis.333,357,411–413”
From American Association of Clinical Endocrinology Clinical Practice Guideline: Developing a Diabetes Mellitus Comprehensive Care Plan-2022 Update. (2022) · cites this paper as [357]
The Results and Conclusions report statin benefits for primary prevention in adults aged 50–75, but neither addresses people requiring dialysis. Searches for dialysis, hemodialysis, and end-stage renal disease found no passage in our copy assessing statin benefit in that population. (LLM, conf=0.76)
Experimental — accuracy not yet measured
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Self-citation
- Authors
- Yourman, L. C., Cenzer, I. S., Boscardin, W. J., Nguyen, B. T., Smith, A. K., Schonberg, M. A., Schoenborn, N. L., Widera, E. W., Orkaby, A., Rodriguez, A., & Lee, S. J.
- Affiliations
- University of California San Diego (US)
- San Francisco VA Medical Center (US)
- Beth Israel Deaconess Medical Center (US)
- Johns Hopkins University (US)
- Brigham and Women's Hospital (US)
- Corresponding author
- Yourman, Lindsey C.
- ORCID
- Venue
- JAMA Internal Medicine
- Publisher
- American Medical Association (AMA)
- Published
- 2021-02-01
- Volume
- 181
- Issue
- 2
- Pages
- 179
- ISSN
- 2168-6106 (ISSN-L)
- PMC
- PMC7670393
- OpenAlex
- W3099949747
- Cited by
- 133
- References
- 57
- Citations by year
- 2026: 25 · 2025: 38 · 2024: 31 · 2023: 16 · 2022: 13 · 2021: 10
- FWCI
- 2.21
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- JAMA Internal Medicine (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- U.S. Department of Veterans Affairs (IK2‐CX001800)
- National Institutes of Health
- National Institute on Aging (R03AG060169, P30AG044281)
- Topics
- Health Sciences › Medicine › Surgery › Lipoproteins and Cardiovascular Health
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Health Promotion and Cardiovascular Prevention
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Antiplatelet Therapy and Cardiovascular Diseases
- Keywords
- statins, primary prevention, major adverse cardiovascular events, older adults, absolute risk reduction, cardiovascular mortality, myocardial infarction, life expectancy, statin therapy
- MeSH terms
- Systematic Reviews as Topic, Cardiovascular Diseases, Humans, Life Expectancy, Primary Prevention, Randomized Controlled Trials as Topic, Hydroxymethylglutaryl-CoA Reductase Inhibitors
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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