There is an urgent need for evidence to guide clinical care of older adults due to demographic shifts, including longer life expectancy and a recent doubling of the older adult population. Statins reduce recurrent CVD events and prevent initial events in patients younger than 75 years. However, clinical research has often excluded persons older than 75 years due to a higher prevalence of comorbidity and frailty so little to no evidence is available to guide care in this population. For older adults living longer, the promise of preventing cognitive impairment is as compelling as preventing a CVD event, but some evidence suggests statins may contribute to memory difficulty or muscle symptoms. There is equipoise regarding the usefulness of statins for primary CVD, dementia, and disability prevention in adults older than 75 years, especially in the setting of multiple chronic conditions, advanced age, or frailty. Evidence to improve cognitive and functional outcomes in older populations with diverse race/ethnicity and health status will require new clinical trial approaches with sustainable methodology and infrastructure. We propose PREVENTABLE (PRagmatic EValuation of evENTs And Benefits of Lipid-lowering in oldEr adults), the first statin trial with a non-CVD primary outcome?survival free of dementia or persisting disability. Using a placebo-controlled pragmatic clinical trial (PCT) design across PCORnet and VA network, the trial will be under the leadership of Dr. Karen Alexander at DCRI, Dr. Jeff Williamson at WFSM, Dr. Adrian Hernandez at DCRI, and Dr. Walter Ambrosius at WFSM. This team has established experience and track-record of accomplishment in the design and conduct of PCTs, trial expertise in ascertaining cognitive and disability outcomes in older adults, and is supported by a robust administrative infrastructure for coordinating these shared responsibilities for success. The overarching goal of PREVENTABLE is to generate knowledge about the role of statins in older adults, a population in which risk/benefit for primary prevention has been under studied. The hypothesis is that a large trial conducted in an older adult population will demonstrate the benefit of statins for reducing dementia, disability, and CV events. We further hypothesize that extensive genomic, biochemical and imaging ancillary studies will offer unique insights into these key outcomes. PREVENTABLE has the following specific aims:
AIM 1 : Determine the role of a moderate-intensity statin in preventing dementia and prolonging disability-free survival in patients 75 years and older without clinically evident coronary heart disease, including those with frailty, impaired physical function, mild cognitive impairment, polypharmacy, and multi-morbidity.
AIM 2 : Determine the role of moderate- intensity statin in preventing hospitalization for myocardial infarction/acute coronary syndrome, stroke, heart failure, revascularization or cardiovascular-related death, and preventing either mild cognitive impairment or dementia.
AIM 3 : Test the safety and tolerability of statins in older adults and collect 17,000 bio-specimens to advance precision health.
PREVENTABLE will evaluate the benefit and risks of moderate-intensity statin for preventing dementia and prolonging disability-free survival in a diverse population of patients 75 years and older without heart disease. We will also evaluate the benefit and risks of moderate-intensity statin use in reducing a cardiovascular outcome (myocardial infarction/acute coronary syndrome hospitalizations, stroke, heart failure, or cardiovascular-related death) or mild cognitive impairment or dementia, and collect lab specimens on 17,000 participants to advance precision health.