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Benefits of Statins in Elderly Revisited: New Meta-Analysis

  • Authors: News Author: Sue Hughes; CME Author: Charles P. Vega, MD
  • CME / ABIM MOC / CE Released: 3/15/2019
  • Valid for credit through: 3/15/2020
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This article is intended for primary care physicians, cardiologists, endocrinologists, geriatricians, nurses, pharmacists, and other clinicians who care for older adults.

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Upon completion of this activity, participants will be able to:

  • Assess the risk for adverse events associated with statins among older adults
  • Analyze the efficacy of statins among older adults
  • Outline implications to the healthcare team


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News Author

  • Sue Hughes

    Freelance News Editor, Medscape LLC


    Disclosure: Sue Hughes has disclosed no relevant financial relationships.

CME Author

  • Charles P. Vega, MD, FAAFP

    Health Sciences Clinical Professor of Family Medicine
    University of California, Irvine School of Medicine
    Irvine, California


    Disclosure: Charles P. Vega, MD, has disclosed the following relevant financial relationships:
    Served as an advisor or consultant for: Johnson & Johnson Pharmaceutical Research & Development, L.L.C.; Sunovion Pharmaceuticals Inc.
    Served as a speaker or a member of a speakers bureau for: Shire

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  • Esther Nyarko, PharmD

    Associate CME Clinical Director, Medscape, LLC


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  • Amy Bernard, MS, BSN, RN-BC, CHCP

    Lead Nurse Planner, Medscape, LLC


    Disclosure: Amy Bernard, MS, BSN, RN-BC, CHCP, has disclosed no relevant financial relationships.

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Benefits of Statins in Elderly Revisited: New Meta-Analysis

Authors: News Author: Sue Hughes; CME Author: Charles P. Vega, MDFaculty and Disclosures

CME / ABIM MOC / CE Released: 3/15/2019

Valid for credit through: 3/15/2020


Clinical Context

Statins are well-known for their ability to reduce the risk for cardiovascular events, particularly as secondary prevention, but the enrollment of older adults in major trials of statins has been low, leading to questions about their efficacy in this important subgroup. Moreover, there is also concern regarding a higher risk for adverse events among older adults taking statins. This latter issue was addressed in a previous meta-analysis by Nanna and colleagues, which was published in the May 8, 2018 issue of the Journal of the American Heart Association.[1]

Researchers assessed a US database of 6717 adults using statins to answer their study question. The rate of statin use for primary prevention was similar among adults age 75 years and younger compared with adults over age 75 years, but the rate of statin use, particularly high-intensity statins, was lower for secondary prevention among persons older than 75 years old.

Adults older than age 75 years were less likely than younger adults to report symptoms related to statin use (41.3% vs 46.6%, respectively; P =.003). The rates of myalgia among older and younger adults were 27.3% and 33.3%, respectively (P <.001). Rates of statin discontinuation because of adverse effects was also similar regardless of age.

The current meta-analysis focused on the efficacy of statin therapy among adults older than age 75 years.

Study Synopsis and Perspective

Statins reduce vascular events in all age groups, including people older than 75 years, according to results of a new meta-analysis from the Cholesterol Treatment Trialists' Collaboration.

"There are robust data on the benefits of statins in preventing premature cardiovascular mortality and morbidity in people aged under 75, but the perception of benefit in the elderly has been unclear as individual trials have not included large numbers in this age group, and consequently, there is underuse of statins in the over 75s," coauthor of the new meta-analysis, Colin Baigent, FRCP, Clinical Trial Service Unit, Nuffield Department of Population Health, Oxford, United Kingdom, told Medscape Medical News.

"By combining data from all relevant trials, our data show a clear benefit in this older age group," Professor Baigent said. "There is a very slight diminution of the relative benefit of statins on vascular events in the elderly compared with younger age groups but the absolute benefits are often greater in the elderly as the risk of vascular death is greater in the older age group."

The meta-analysis, which summarizes evidence from 28 randomized controlled trials including 186,854 patients, 14,483 (8%) of whom were older than age 75 years, was published online February 2 in The Lancet.[2]

Professor Baigent believes that society is not focused enough on preventive medical care in the elderly. "We can be somewhat ageist in our approach," he said. "Our attitude seems to be that their time has been -- that it is not worth treating them with preventative medication. But every old person's greatest fear is having a stroke and being disabled and dependent. This is unhealthy aging. Statins can reduce that risk."

In addition to stroke, reducing the incidence of myocardial infarction will also reduce heart failure, further contributing to healthy aging, he said.

"These drugs are cheap and safe," he added, "and our data show they should be used much more widely in the elderly population."

He estimated that statins are currently being taken by about one-third of individuals older than age 75 in the United Kingdom.

"We could save several thousand premature deaths and vascular events in the UK alone by increasing the number of elderly on statins," he said.

For the meta-analysis, the researchers analyzed individual participant data from 22 trials and detailed summary data from one trial of statin therapy vs control, plus individual participant data from 5 trials of more intensive vs less intensive statin therapy, with a median follow-up in all trials of 4.9 years.

Participants were divided into 6 age groups (≤55 years, 56-60 years, 61-65 years, 66-70 years, 71-75 years, and >75 years). Effects of statins on major vascular events, cause-specific mortality, and cancer incidence were estimated and compared in the different age groups.

Results showed that, overall, statin therapy or a more intensive statin regimen produced a 21% proportional reduction in major vascular events per 1.0-mmol/L reduction in low-density lipoprotein cholesterol (LDL-C) (risk ratio [RR]=0.79).

Significant reductions in major vascular events were seen in all age groups, and although proportional reductions in major vascular events diminished slightly with age, this trend was not significant (P trend =.06).

Overall, statin or more intensive therapy yielded a 24% proportional reduction in major coronary events per 1.0-mmol/L reduction in LDL-C (RR-0.76), and there was a trend towards smaller proportional risk reductions with increasing age (P trend =.009).

Statin use or a more intensive statin regimen was also linked to a 25% proportional reduction in the risk for coronary revascularization procedures with statin therapy per 1.0-mmol/L lower LDL-C (RR=0.75), which did not differ significantly across age groups (P trend =.6).

Similarly, the proportional reductions in stroke of any type (RR=0.84) did not differ significantly across age groups (P trend =.7).

After exclusion of 4 trials that enrolled only patients with heart failure or undergoing renal dialysis (among whom statin therapy has not been shown to be effective), the trend to smaller proportional risk reductions with increasing age persisted for major coronary events (P trend =.01) and remained nonsignificant for major vascular events (P trend =.3).

The proportional reduction in major vascular events was similar, irrespective of age, among patients with preexisting vascular disease (P trend =.2) but appeared smaller among older than younger individuals not known to have vascular disease (P trend =.05).

There was a 12% proportional reduction in vascular mortality per 1.0 mmol/L reduction in LDL-C (RR=0.88), with a trend toward smaller proportional reductions with older age (P trend =.004), but this trend did not persist after exclusion of the heart failure or dialysis trials (P trend =.2).

Statin therapy had no effect at any age on nonvascular mortality, cancer death, or cancer incidence.

What About Primary Prevention?

In their discussion, the researchers noted that previous meta-analyses among older people have consistently reported evidence for beneficial effects in secondary prevention, but the evidence has been less clear for primary prevention. They said that the availability of individual participant data in this meta-analysis has permitted more detailed assessment of the effects of statin therapy at different ages.

They reported that their results show smaller proportional risk reductions in persons with no known vascular disease (the primary prevention population) compared with persons with established vascular disease (the secondary prevention population). No independently significant reductions were found in patients older than 70 years, but there were not enough events in the older age group of the primary prevention population for definitive answers, they noted. Further trials in this population are ongoing.

"In our study there was more limited evidence in the primary prevention context, but given the clear evidence overall that the relative benefits were similar irrespective of age and the consistency of the effects at all ages in primary prevention, it is reasonable to infer that statins are likely to be effective for primary prevention in those aged over 75," Professor Baigent told Medscape Medical News.

In The Lancet article, the authors emphasized that even if the proportional reductions in major vascular events brought about by statins diminishes slightly with increasing age, the untreated absolute risks increase exponentially with age, so the absolute benefits of a given reduction in LDL-C with statin therapy would be expected to be substantially greater among older individuals.

They gave an example in the primary prevention setting of 2 individuals aged 63 years and 78 years with otherwise identical risk factors who might have projected major vascular event rates of 2.5% vs 4.0% per year, respectively. Reducing those risks by a fifth by reducing LDL-C by 1.0 mmol/L would prevent a first major vascular event from occurring each year in 50 individuals age 63 years and 80 individuals age 78 years per 10,000 people treated, they reported.

"Obviously, there are some people for whom these drugs will be inappropriate -- those on other medications which cause interactions or if they have a very limited lifespan due to cancer or another terminal condition," Professor Baigent added. "We also know statins don't benefit patients with heart failure -- probably because these patients mainly die of pump failure or sudden arrhythmic death, which statins do not influence. But for many of the others in the older population, it appears they will benefit as much as -- if not more than -- younger patients."

'Misinformation' About Adverse Effects?

On the issue of the adverse effects of statins, Professor Baigent believed there has been a lot of misinformation.

"Much of this confusion arises from potentially biased observational studies, which are not able to provide reliable information," he said. "The perception that statins cause troublesome problems like muscle pain is just that -- a perception. Muscle pain is very common and the randomized trial evidence has demonstrated very clearly that the vast majority of muscle symptoms that occur in people taking a statin are not caused by the drug."

He added, "The randomized trial evidence, which is unbiased and should be the sole source of information that we trust to guide practice, indicates that statins do cause myopathy (rarely rhabdomyolysis), a slightly increased risk of diabetes, and hemorrhagic stroke. The excess risk of all known adverse effects is very small (for example, the incidence of myopathy is about 1 in 10,000 per year) and far exceeded by the benefits of statin therapy.

"Although the absolute risks of these adverse effects are higher in the elderly, so too are the absolute risks of vascular disease, so the overall balance of benefit and risk is still heavily weighted towards benefit in those aged over 75," Professor Baigent concluded.

In an accompanying editorial,[3] Bernard M.Y. Cheung, MB BChir, PhD, and Karen S.L. Lam, MD, Queen Mary Hospital, University of Hong Kong, pointed out some limitations of the new meta-analysis.

These include that the patients in trials are "highly selected, with fewer comorbidities, less drug intolerance, and better adherence than the general patient population," and "the included clinical trials concentrated on efficacy endpoints -- adverse events, especially if nonserious, were not as fully recorded and analyzed, which limited the ability of this meta-analysis to develop insights into the risks of side effects for older people with statins."

The editorialists said that more research in older people is needed to enrich the evidence on the risks and benefits of statins.

They said the benefits of statins in the prevention of major vascular events have been shown to be much greater than their risks, and the present meta-analysis, which includes people older than standard trial populations, echoed this conclusion, but they added that when statins are used in people with low cardiovascular risk, the risks and benefits need to be weighed against each other.

"The challenge for the healthcare profession and the media is to convey risks and benefits in ways that patients can understand, enabling them to make an informed choice," they noted.

The meta-analysis was supported by the Australian National Health and Medical Research Council, National Institute for Health Research Oxford Biomedical Research Centre, UK Medical Research Council, and British Heart Foundation. Disclosures for the authors are listed with the article.

Study Highlights

  • Researchers assessed randomized trials featuring statins that included ≥1000 participants and scheduled follow-up for ≥2 years. The focus of the current analysis included major coronary events, coronary revascularization, stroke, incident cancer, and mortality.
  • These outcomes were assessed according to the age of participants in the current analysis, with specific attention to adults >75 years old.
  • 28 trials featuring a total of 186,854 individuals were included in the current analysis. Most of the cohort was male.
  • A strong majority of trials compared statins with placebo, but 5 trials compared low-dose with intensive statin regimens.
  • Only 8% of participants in the research cohort were >75 years old. Older participants were more likely to be female and have heart failure and hypertension compared with younger adults.
  • Baseline levels of LDL-C were lower as the age of study participants increased, and statins were marginally less effective at lowering LDL-C among older adults.
  • Across the studies, each 1.0-mmol/L reduction in LDL-C related to statin use was associated with an RR of 0.79 (95% CI: 0.77, 0.81) for a first major vascular event.
  • There was a nonsignificant trend toward lower efficacy of statins in reducing the risk for a first major vascular event among adults >75 years old. This trend was less pronounced when trials that focused exclusively on heart failure and end-stage renal disease, which featured higher concentrations of older adults, were excluded from analysis. Previous research has found that statins are not effective in the prevention of vascular events among adults with heart failure and end-stage renal disease.
  • The RR for major coronary events associated with each 1.0-mmol/L reduction in LDL-C because of statin therapy was 0.76 (95% CI: 0.73, 0.79). There was a significant trend toward less efficacy of statins with increasing age in this outcome, but statins remained effective for adults >75 years old.
  • The RR for revascularization procedures associated with each 1.0-mmol/L reduction in LDL-C because of statin therapy was 0.75 (95% CI: 0.73, 0.78). Age did not appear to affect this outcome, although the number of procedures performed on adults >75 years was quite small.
  • The RR for vascular mortality associated with each 1.0-mmol/L reduction in LDL-C because of statin therapy was 0.88 (95% CI: 0.85, 0.91), with no effect of age on this outcome.
  • Statins did not significantly affect the risk for nonvascular mortality.
  • Statins were more effective at preventing vascular events among older adults with a history of previous vascular disease vs no such history, but the number of older adults receiving statins as primary prevention was relatively low.
  • Statins were not associated with a higher risk for cancer in any age group.

Clinical Implications

  • A previous study by Nanna and colleagues found that adults older than 75 years were less likely than younger adults to receive a high-dose statin, but older adults were less likely to report a symptom related to statin use and myalgias specifically. Rates of statin discontinuation because of adverse events was not affected by age.
  • The current meta-analysis by the Cholesterol Treatment Trialists’ Collaboration demonstrates that statins can improve rates of vascular events among adults older than age 75 years, with the greatest effect among older adults with a history of vascular disease. Age did not significantly affect an improved risk for death because of vascular causes associated with statins, and statins were not associated with a higher incidence of cancer.
  • Implications for the Healthcare Team: The healthcare team should weigh the risks and benefits of statin therapy for each patient. The current study suggests that statins should be recommended to adults older than age 75 years with known vascular disease.

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