Statin use in the Elderly
Statin therapy has been shown to reduce the risk of vascular events in younger individuals with manifest atherosclerotic disease or at high risk of vascular events. However, data derived from individual participant meta-analyses of existing trials suggest that the efficacy of statins may decline substantially amongst those over 70 years of age. There have been insufficient participants of this age group included in major trials to be certain of the benefit. Given the potential for widespread use of statins amongst this age group, the data emphasises the need for more certainty about the scale of any likely benefit of this class of drugs.
An Ageing Population
The rationale for undertaking a trial of statins in the elderly is not only based on the high proportion of elderly people affected by new guidelines introduced in the US and UK (which state that anyone with an increased risk of cardiovascular disease should be on a statin for primary prevention), but also by the predicted increase in the ageing population. Resolving the question about a therapy with such potential for near universal use is therefore of increasing importance for future generations.
Statins (HMG-CoA reductase inhibitors) are a class of drugs with a potential to delay the onset of several causes of incapacity in the elderly especially vascular disease. Their best-recognised action is to reduce circulating blood lipid levels1. However, there is no clear effect of statins on the risk of death, dementia or disability.
Adverse effects: Adverse effects of statins include myopathy, development of diabetes, cancer and cognitive impairment, all of which have particular relevance to drug use in the elderly. This burden of adverse effects of drug therapy is greater in older people, and is compounded by poly-pharmacy, drug interactions and the costs of treatment3.
Fundamental question of risk versus benefit: The use of statins in the over 70 age group raises fundamental questions about the purpose of preventive drug therapy in this older age group. When a preventive agent is used in the context of competing mortality, polypharmacy and a higher incidence of adverse effects its use should be justified by an improvement in quality of life or some other composite measure that demonstrates that the benefit outweighs other factors. Prevention of a single component of a complex mix of positive and negative effects of a drug will increasingly be seen to provide inadequate justification for widespread use, especially in older people. Without an appropriately designed clinical trial it is not possible to know the balance of risks and benefits associated with the use of these agents in this age-group.
STAREE will utilise the resources and expertise in community-based research established in the Australian National Blood Pressure Study (ANBP2) trial and subsequently adapted for the randomised controlled trial of Aspirin in Reducing Events in the Elderly (ASPREE). Funded by the Australian National Health and Medical Research Council (NHMRC) and the US National Institute of Health (NIH) ASPREE has recruited over 18,000 patients and published major findings in September 2018.
Hypotheses and aims
Hypotheses: Treatment with statin (atorvastatin 40mg) compared with placebo will not prolong overall disability free survival amongst a healthy elderly population (≥70 years).
Treatment with statin (atorvastatin 40mg) compared with placebo will not reduce the incidence of major adverse cardiovascular events amongst a healthy elderly population (≥70 years).
Aims: To determine in people aged ≥70 years the effect of statin therapy (40 mg atorvastatin) versus placebo, over an average 5-year treatment period, for the prevention of two co-primary clinical endpoints; (i) a composite of all-cause mortality or dementia or development of disability and; (ii) major adverse cardiovascular events (myocardial infarction, stroke and cardiovascular death).
The study will be a double-blind, randomised, placebo-controlled trial involving men and women over 70 years of age. It will utilise the infrastructure established for the ASPREE trial and follow similar recruitment and follow-up procedures.
Outcomes and Significance
This study will be the first randomised controlled trial (RCT) of statin therapy in an apparently healthy elderly cohort (aged 70 years and over) living independently in the community. Although previous trials have reported benefits of statin therapy on cardiovascular outcomes in younger people with established cardiovascular disease or at high risk of cardiovascular disease, none have focused on the balance of benefits and risks in older people. Given the demographic transition to an ageing population and the increasing health care costs incurred by governments and individuals, this study has the potential to influence health expenditure in Australia and to change the way that preventive drugs are evaluated in this age group.
The present study is important because there is often only a limited time window to study the efficacy and safety of new clinical trends before they become almost irreversibly entrenched into clinical practice.
1. Stancu C, Sima A. Journal of Cell and Mol Med. 2001;5(4):378-87.
4. Mihaylova B, et al. Lancet. 2012;380(9841):581-90.
3. Routledge PA, O’Mahony MS, Woodhouse KW. Br J Clin Pharmacol. 2004;57(2):121-6.