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EXPERT REACTION: Questions raised over benefits of statins for the elderly

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A European study has questioned the widespread use of statins in healthy older people to prevent heart disease and stroke. Statin prescriptions to elderly patients have increased in recent decades - mostly for people aged 75 years or older with existing heart disease. The researchers say their study shows there is no reason why those without heart disease should take statins, unless they also have type 2 diabetes and are aged between 75 and 84. An accompanying editorial says that since the study is observational, for now, "patient preference remains the guiding principle while we wait for better evidence”.

Journal/conference: The BMJ

Link to research (DOI): 10.1136/bmj.k3359

Organisation/s: University of Girona, Spain

Media Release

From: The BMJ

New study does not support widespread use of statins in healthy older people to prevent heart disease and stroke

Any protective effect was limited to those with type 2 diabetes aged between 75 and 84

Statins are not associated with a reduction in cardiovascular disease (conditions affecting the heart and blood vessels) or death in healthy people aged over 75, finds a study published by The BMJ today.

However, in those with type 2 diabetes, statins were related to a reduction in cardiovascular disease and death from any cause up to the age of 85 years.

The results of the study, led by the University Institute for Primary Care Research Jordi Gol (IDIAPJGol) and Girona Biomedical Research Institute (IDIBGI), do not support the widespread use of statins in old and very old people, but they do support treatment in selected people, such as those aged 75-84 years with type 2 diabetes, say the researchers.

Cardiovascular disease is the leading cause of death globally, especially for those aged 75 and over. Statin prescriptions to elderly patients have increased in recent decades, and trial evidence supports statin treatment for people aged 75 years or older with existing heart disease (known as secondary prevention).

But evidence on the effects of statins for older people without heart disease (known as primary prevention) is lacking, particularly in those aged 85 years or older and those with diabetes.

So researchers based in Spain set out to assess whether statin treatment is associated with a reduction in cardiovascular disease and death in old (75-84 years) and very old (85 years and over) adults with and without type 2 diabetes.

Using data from the Catalan primary care system database (SIDIAP), they identified 46,864 people aged 75 years or more with no history ofcardiovascular disease between 2006 and 2015.

Participants were grouped into those with and without type 2 diabetes and as statin non-users or new users (anyone starting statins for the first time during the study enrollment period).

Primary care and hospital records were then used to track cases of CVD (including coronary heart disease, angina, heart attack and stroke) and death from any cause (all cause mortality) over an average of 5.6 years.

In participants without diabetes, statin treatment was not associated with a reduction in CVD or all cause mortality in both old and very old age groups, even though the risk of CVD in both groups was higher than the risk thresholds proposed for statin use in guidelines.

In participants with diabetes, however, statins were associated with significantly reduced levels of CVD (24%) and all cause mortality (16%) in those aged 75-84 years. But this protective effect declined after age 85 and disappeared by age 90.

This was an observational study, so no firm conclusions can be drawn about cause and effect, and the authors cannot not rule out the possibility that some of their results may be due to unmeasured (confounding) factors.

But they point out that this was a high quality study with a large sample size, reflecting real life clinical conditions.

A such, they conclude that their results do not support the widespread use of statins in old and very old populations, but they do support treatment in those with type 2 diabetes younger than 85 years.

In a linked editorial, Aidan Ryan at University Hospital Southampton and colleagues, say the biggest challenge for clinicians is how to stratify risk among those aged more than 75 to inform shared decision making.

These observational findings should be tested further in randomised trials, they write. In the meantime, they say “patient preference remains the guiding principle while we wait for better evidence.”

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Expert Reaction

These comments have been collated by the Science Media Centre to provide a variety of expert perspectives on this issue. Feel free to use these quotes in your stories. Views expressed are the personal opinions of the experts named. They do not represent the views of the SMC or any other organisation unless specifically stated.

Professor John McNeil AM is is Head of the School of Public Health and Preventive Medicine at Monash University

Recent clinical guidelines in both the US and UK have increased the number of individuals for whom statins are recommended. However these guidelines make no recommendations about the potential value of these agents for people free of heart disease or stroke who are over 75.

Although this data is  observational, and not as reliable as a clinical trial, it casts some doubt about the value of this medication in non-diabetic adults beyond 75 who do not have a specific reason to be taking them.

However it is by no means the last word on the subject and emphasises the importance of large-scale studies such as the Australian STAREE trial to resolve this question more definitively.

Last updated: 04 Sep 2018 8:38pm
Declared conflicts of interest:
None declared.

A/Prof Mark Jones is a biostatistician from Bond University with experience at conducting an observational study of statins in elderly Australian women

From a statistical point-of-view, the Ramos, et al. observational study appears to have been well conducted and reported. However, it is an observational study which is more prone to bias than randomised controlled trials.

Given this limitation, the authors have quite appropriately stated 'These results, based on observational data, may not provide enough grounds for direct clinical recommendations, but they do show the need for randomised clinical trials to further elucidate this problem.'

This study adds to a very limited number of studies on statin use in elderly patients which have consistently shown limited benefits for those without established cardiovascular disease.

A novel aspect of the Ramos, et al. study is the stratification by diabetes status leading to the finding that statins appear to have a beneficial effect in patients with type 2 diabetes aged 75 to 84, although the absolute effect sizes are modest e.g. 306 patients would need to be treated with statins to prevent one additional death from any cause.

Last updated: 04 Sep 2018 8:37pm
Declared conflicts of interest:
None declared.

Professor Garry Jennings AO is Executive Director, Sydney Health Partners

As a retrospective cohort study, definitive conclusions regarding the effectiveness of statin treatment cannot be drawn.

There is no valid control group in the study.  People aged over 75 whose doctors felt they needed statins had the same risk as people whose doctors did not, unless they had diabetes, in which case they did better.  Perhaps the doctors got it right!

There may well be other subsets within the aged community who, like those with diabetes are at high risk. 

Presently used methods of assessing the level of risk are so dominated by the effect of age itself that it is not possible to identify grades of risk within the population of older people.  This is a major priority if we are to better target prevention therapies to those who will benefit the most. 

Although the results were adjusted for known confounders, this cannot rule out the impact of unknown confounders. The results are also limited by the potential for a ‘survival effect’, meaning that older patients (> 75 years) included in the study were less likely to develop cardiovascular disease.

Further research is required (and underway) regarding the use of statins for primary prevention in patients aged 85 years or older, given the limited sample size in this study, and the fact that there is generally uncertainty about the balance of risk and benefits of statin therapy in healthy older people.

Statins are indicated for primary prevention for selected patients to reduce cardiovascular risk although clear evidence in people aged >75 years old is lacking.  This does not change in the light of this study. 

I think the Journal and press release overreached but the authors got it right in their discussion:

'These results, based on observational data, may not provide enough grounds for direct clinical recommendations, but they do show the need for randomised clinical trials to further elucidate this problem. Statins for Reducing Events in the Elderly (STAREE study) is a promising ongoing trial on CVD primary prevention that compares atorvastatin (40 mg) with placebo in healthy people older than 70 years,54 but until publication of the STAREE results, expected in 2022, our findings may help to make decisions in clinical practice.'

STAREE is of course run from Australia by the Monash Department of Epidemiology and Preventive Medicine.

Last updated: 04 Sep 2018 8:39pm
Declared conflicts of interest:
None declared.
Dr David Colquhoun is a Clinical Cardiologist practising at the Wesley & Greenslopes Private Hospital and Associate Professor of Medicine at the University of Queensland.

This study that interrogated a Spanish information system that correlated at least two invoices for statins from July 2006 to December 2007 with records from general practitioners in Catlin, Spain, has not provided any useful information regarding the benefits of lipid lowering in the elderly.  By the nature of this computer-based auditing, one has no idea whether or not the patients took their drugs, and more importantly whether there was a change in lipid levels. 

It is the weakest form of research, linking prescriptions to databases, and is not designed to accurately assess cardiovascular outcomes.  The message written under ‘What this study adds’ is unsupported.  It is likely to lead to a negative statin story which has been well documented to have consequences.  After the incorrect Catalyst story in Australia it was documented that about 1.5 million people watched the programme and between 1,500 and 3,000 patients had a heart attack or stroke who otherwise would not have had such events. 

It is difficult to understand how a respected medical journal such as The BMJ could publish poor research and allow unsubstantiated statements to be made which have important consequences regarding cardiovascular health.

To assess efficacy of lipid-lowering therapy, one needs to do a properly designed clinical trial.  This has been done in over 300,000 individuals in more than 30 trials.  It is clear that it is unimportant what type of therapy one has to lower LDL, be it partial ilial bypass surgery, Ezetimibe, bile sequestrants, statins, or the new PCSK-9  monoclonal antibody inhibitors.  Irrespective of therapy for every 1 mmol reduction of LDL there is approximately 25 per cent less heart attacks, 20 per cent less strokes, and 10 per cent decreased total mortality. In the randomised trials, reviews of patients across all age brackets, including the elderly, have the same relative risk reduction. What is clear, in the very elderly, lipid lowering therapy and more specifically lowering of LDL-cholesterol, decreases heart attacks, but if there is a high competing cause of mortality then there is no decrease in total deaths. 

What this study tells us is there is no substitute for good science and good clinical trials, and retrospective analysis of invoices of prescriptions linked to databases of unknown accuracy is not useful to assess the efficacy of lipid-lowering drug therapy.  There is no substitute for good science.

The statement in the paper by the authors is wrong. This ‘study’ does not add anything at all to the literature regarding efficacy of lipid lowering therapy. Absolutely this study should not be used to support the ‘arguments’. This is not a research study it is ‘data dredging’ from computer records.

Last updated: 05 Sep 2018 3:37pm
Declared conflicts of interest:
Commercial (in past 2 years): Boehringer-Ingelheim, AmGen, Vifor, Novartis, Sanofi, Eli Lilly, Pfizer, BMS, Astra Zeneca, MSD, Abbott, Sanitorium, Swisse Vitamins. Professional (in past 2 years) National Board Member - National Heart Foundation of Australia (NHFA); Scientific Committees - National Institute of Complementary Medicine and Gallipoli Medical Research Foundation; Co-President - Clinical and Preventative Cardiology Council of the Cardiac Society of Australia and New Zealand (CSANZ)

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