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PREVENTABLE: Pragmatic Evaluation of Events and Benefits of Lipid-lowering in Older Adults

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, but these exclusions are based on faulty assumptions and have resulted in little to no evidence 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. However, evidence to improve disability-free survival in older populations will require new clinical trial approaches with sustainable methodology and infrastructure to ascertain cognitive and functional outcomes in a large population of older adults of diverse race/ethnicity and health status. There is evidence that treating hyperlipidemia may protect against vascular cognitive impairment and risk for Alzheimer's disease and related dementias (ADRD), but reports also suggest statins can contribute to cognitive impairment. There is a strong relationship between CVD and physical function decline, but prior statin trials excluded older adults so the ability to preserve physical function with effective vascular prevention is unknown. Given the heterogeneity in health status among older persons, some subgroups of older adults may benefit from statins to prevent future CV events, but others may not. Therefore, 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. We propose PREVENTABLE (PRagmatic EValuation of evENTAnd 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 Veterans Affairs health care systems, we will evaluate the risks and benefits of a moderate-intensity statin on important health outcomes for older adults. 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 over unique insights into these key outcomes. This trial will support evidence-based care of millions of older adults excluded from prior trials - identifying those who may benefit and those have only risks. In this context, 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. 

 


 

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