Clinician Article

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

  • Yourman LC
  • Cenzer IS
  • Boscardin WJ
  • Nguyen BT
  • Smith AK
  • Schonberg MA, et al.
JAMA Intern Med. 2020 Nov 16. pii: 2773065. doi: 10.1001/jamainternmed.2020.6084. (Review)
PMID: 33196766
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  • Geriatrics
    Relevance - 6/7
    Newsworthiness - 6/7
  • Internal Medicine
    Relevance - 6/7
    Newsworthiness - 6/7
  • Public Health
    Relevance - 6/7
    Newsworthiness - 6/7
  • Family Medicine (FM)/General Practice (GP)
    Relevance - 5/7
    Newsworthiness - 6/7
  • General Internal Medicine-Primary Care(US)
    Relevance - 5/7
    Newsworthiness - 6/7
  • Cardiology
    Relevance - 5/7
    Newsworthiness - 5/7


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.

Clinical Comments


Clinicians are often challenged to determine which medications are likely to benefit older patients with limited life expectancy. This article suggests that older patients are unlikely to benefit from statins for primary prevention of heart disease unless they have at least 2.5 years of life expectancy. This is clinically useful information that can help practitioners make evidence-based and cost-effective prescribing decisions.

Internal Medicine

This paper raises a very relevant clinical question: What is the time to benefit for cardiovascular prevention with statin treatment. It followed a very rigorous approach to answer the question. The authors provide a very interesting discussion about individualizing treatment decisions.

Public Health

The benefit of this article to me as a hospitalist is that it provides evidence when I am asked to give an opinion or advice to my colleagues.

Public Health

It's important to highlight that statins are beneficial for most patients to reduce CV outcomes and we should not necessarily aim for a mortality benefit. The benefits outweigh harms in primary prevention, also in populations >55 years.

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