Independent Living, Disability Free Survival, Elderly, Healthy
Conditions
Keywords
Survival, Functional Disability, Cardiovascular Disease, Diabetes, Dementia, Cancer
Brief summary
The STAREE study will examine whether treatment with statin (atorvastatin 40mg) compared with placebo will prolong disability free survival and reduce major cardiovascular events amongst healthy elderly people (≥70 years).
Detailed description
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 meta-analyses of existing trials suggests that the efficacy of statins may decline sharply amongst those over 70-75 years of age. Insufficient patients of this age group have been included in major trials to be certain of the benefit. Within this age group part of the benefit of statin therapy may be offset by adverse effects including myopathy, development of diabetes, cancer and cognitive impairment, all of which are more prevalent in the elderly in any event. The use of statins in the over 70 age group raises fundamental questions about the purpose of preventive drug therapy in this 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. STAREE will determine whether taking daily statin therapy (40 mg atorvastatin) will extend the length of a disability-free life, determined from survival outside permanent residential care, in healthy participants aged 70 years and above.
Interventions
DRUGAtorvastatin
Atorvastatin 20 mg tablet
Inactive pill manufactured to mimic Atorvastatin 20 mg tablet
Sponsors
National Health and Medical Research Council, Australia
National Heart Foundation, Australia
Monash University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
70 Years to No maximum
Healthy volunteers
Yes
Inclusion criteria
* Men and women aged ≥70 years living independently in the community * Willing and able to provide informed consent and accept the study requirements (Note: competent physical ability to participate in the trial is assessed using the KATZ ADL questionnaire)
Exclusion criteria
A history of cardiovascular disease (defined as myocardial infarction, stroke, peripheral vascular disease, angina, transient ischaemic attack, coronary artery angioplasty and/or stenting, coronary artery bypass grafting, carotid stenosis, abdominal aortic aneurysm or heart failure), * A history of dementia or a 3MS score \<78 on screening, * A history of diabetes, * Total cholesterol \>7.5 mmol/L, * Moderate or severe chronic kidney disease (persistent proteinuria (Urine albumin:creatinine ratio \>30mg/mmol or Urine protein:creatinine ratios \>45 mg/mmol)45 and/or eGFR \<45ml/min/1.73m2), * Moderate or severe liver disease (persistent elevations of transaminases of more than 3 times the upper limit of the normal laboratory reference range), * Serious inter-current illness likely to cause death within the next 5 years such as terminal cancer or obstructive airways disease, * Current participation in a clinical trial, * Absolute contraindication to statin therapy, * Current use of statin therapy or other lipid lowering therapy for primary prevention and unwilling to stop therapy, * Current long term or permanent use of the following cytochrome P450 (CYP) 3A4 inhibitors : Amiodarone, Boceprevir, Cimetidine, Cyclosporin, Danazol, Fosamprenavir, Indinavir, Lopinavir + Ritonavir, Erythromycin, Fluconazole, Itraconazole, Ketoconazole.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Major cardiovascular events | Time from randomisation to a primary endpoint or censoring at the end of study follow-up which is anticipated to be an average 6 years. | Defined as the first occurrence of a cardiovascular death or a non-fatal myocardial infarction or stroke or coronary revascularisation |
| Disability free survival - death or development of dementia or development of persistent physical disability | Time from randomisation to a primary endpoint or censoring at the end of study follow-up which is anticipated to be an average 6 years. | Defined as survival free of dementia or persistent physical disability (as derived from the endpoints of all-cause mortality, dementia and physical disability) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Cardiovascular death | Time from randomisation to a secondary endpoint or censoring at the end of study follow-up which is anticipated to be an average 6 years. | Fatal cardiovascular events |
| Fatal and Non-fatal Mycocardial infarction | Time from randomisation to a secondary endpoint or censoring at the end of study follow-up which is anticipated to be an average 6 years. | Fatal and non-fatal |
| Hospitalisations | Time from randomisation to a secondary endpoint or censoring at the end of study follow-up which is anticipated to be an average 6 years. | Hospitalisation reasons and length of stay |
| Fatal and Non-fatal Cancer | Time from randomisation to a secondary endpoint or censoring at the end of study follow-up which is anticipated to be an average 6 years. | Fatal and Non-fatal Cancer (excluding non-melanoma skin cancer) |
| Other cognitive impairment | Time from randomisation to a secondary endpoint or censoring at the end of study follow-up which is anticipated to be an average 6 years. | Cognitive decline as assessed using cognitive tests excluding depression |
| Quality of life measured by the Short Form Health Survey (SF-36) | Time from randomisation to a secondary endpoint or censoring at the end of study follow-up which is anticipated to be an average 6 years. | Quality of life (measured by the Short Form Health Survey (SF-36) administered at every second year of follow-up). |
| Cost-effectiveness of statin | Time from randomisation to a secondary endpoint or censoring at the end of study follow-up which is anticipated to be an average 6 years. | Cost-effectiveness of statin |
| Approved need for permanent residential care | Time from randomisation to a secondary endpoint or censoring at the end of study follow-up which is anticipated to be an average 6 years. | ACAS report |
| Dementia | Time from randomisation to a secondary endpoint or censoring at the end of study follow-up which is anticipated to be an average 6 years. | All-cause dementia (COWAT, Stroop test, Trail Making Test, HVLT-R, SDMT, ADAS-Cog, Lurian overlapping figures) or external diagnosis |
| Persistent physical disability | Time from randomisation to a secondary endpoint or censoring at the end of study follow-up which is anticipated to be an average 6 years. | KATZ-ADL administered every 6 months or external diagnosis |
| All cause death | Time from randomisation to a secondary endpoint or censoring at the end of study follow-up which is anticipated to be an average 6 years. | All cause death |
| Heart failure | Time from randomisation to a secondary endpoint or censoring at the end of study follow-up which is anticipated to be an average 6 years. | Heart failure |
| Atrial fibrillation | Time from randomisation to a secondary endpoint or censoring at the end of study follow-up which is anticipated to be an average 6 years. | Atrial fibrillation |
| Revascularisation procedure | Time from randomisation to a secondary endpoint or censoring at the end of study follow-up which is anticipated to be an average 6 years. | Revascularisation procedure including coronary revascularisation |
| Fatal and Non-fatal Stroke | Time from randomisation to a secondary endpoint or censoring at the end of study follow-up which is anticipated to be an average 6 years. | Fatal and Non-fatal Stroke can be a) haemorrhagic or b) thromboembolic |
| A composite of cardiovascular death, non-fatal myocardial infarction or non-fatal stroke | Time from randomisation to a secondary endpoint or censoring at the end of study follow-up which is anticipated to be an average 6 years. | A composite of cardiovascular death, non-fatal myocardial infarction or non-fatal stroke |
Other
| Measure | Time frame | Description |
|---|---|---|
| New onset diabetes | Time from randomisation to a secondary endpoint or censoring at the end of study follow-up which is anticipated to be an average 6 years. | New diagnosis of diabetes |
Countries
Australia
Outcome results
None listed