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Randomized Controlled Trial
. 2023 Jun;71(6):1701-1713.
doi: 10.1111/jgs.18312. Epub 2023 Apr 20.

Pragmatic evaluation of events and benefits of lipid lowering in older adults (PREVENTABLE): Trial design and rationale

Jacob Joseph  1 , Nicholas M Pajewski  2 , Rowena J Dolor  3 , Mary Ann Sellers  3 , Letitia H Perdue  2 , Sheronda R Peeples  4 , Adam M Henrie  5 , Nancy Woolard  2 , W Schuyler Jones  3 , Catherine P Benziger  6 , Ariela R Orkaby  7 , Amanda S Mixon  8 , Jeffrey J VanWormer  9 , Michael D Shapiro  2 , Christine E Kistler  10 , Tamar S Polonsky  11 , Ranee Chatterjee  3 , Alanna M Chamberlain  12 , Daniel E Forman  13 , Kirk U Knowlton  14 , Thomas M Gill  15 , L Kristin Newby  3 , Bradley G Hammill  3 , Mine S Cicek  12 , Neely A Williams  16 , Jake E Decker  17 , Jiafu Ou  18 , Jack Rubinstein  19 , Gaurav Choudhary  20 , Raúl J Gazmuri  21 , Kenneth E Schmader  22 , Christianne L Roumie  8 , Camille P Vaughan  23 , Mark B Effron  24 , Rhonda M Cooper-DeHoff  25 , Mark A Supiano  26 , Raj C Shah  27 , Jeffrey C Whittle  28 , Adrian F Hernandez  3 , Walter T Ambrosius  2 , Jeff D Williamson  2 , Karen P Alexander  3 ; PREVENTABLE Trial Research Group
Collaborators, Affiliations
Randomized Controlled Trial

Pragmatic evaluation of events and benefits of lipid lowering in older adults (PREVENTABLE): Trial design and rationale

Jacob Joseph et al. J Am Geriatr Soc. 2023 Jun.

Abstract

Whether initiation of statins could increase survival free of dementia and disability in adults aged ≥75 years is unknown. PREVENTABLE, a double-blind, placebo-controlled randomized pragmatic clinical trial, will compare high-intensity statin therapy (atorvastatin 40 mg) with placebo in 20,000 community-dwelling adults aged ≥75 years without cardiovascular disease, disability, or dementia at baseline. Exclusion criteria include statin use in the prior year or for >5 years and inability to take a statin. Potential participants are identified using computable phenotypes derived from the electronic health record and local referrals from the community. Participants will undergo baseline cognitive testing, with physical testing and a blinded lipid panel if feasible. Cognitive testing and disability screening will be conducted annually. Multiple data sources will be queried for cardiovascular events, dementia, and disability; survival is site-reported and supplemented by a National Death Index search. The primary outcome is survival free of new dementia or persisting disability. Co-secondary outcomes are a composite of cardiovascular death, hospitalization for unstable angina or myocardial infarction, heart failure, stroke, or coronary revascularization; and a composite of mild cognitive impairment or dementia. Ancillary studies will offer mechanistic insights into the effects of statins on key outcomes. Biorepository samples are obtained and stored for future study. These results will inform the benefit of statins for increasing survival free of dementia and disability among older adults. This is a pioneering pragmatic study testing important questions with low participant burden to align with the needs of the growing population of older adults.

Trial registration: ClinicalTrials.gov NCT04262206.

Keywords: cognition; dementia; healthy aging; older adults; statins.

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Conflict of interest statement

Thomas M. Gill is supported by P30AG021342 and 5UL1TR001863. Dr. Pajewski is supported by P30AG021332, R01HL155396, and R01AG071807. Dr Roumie is supported in part by CX000570-10 and the Center for Diabetes Translation Research P30DK092986.

Daniel E. Forman is supported by NIH awards R01AG060499, R01AG058883, and P30AG02482, and VHA MERIT award I01HX003518.

L. Kristin Newby reports research funding from NHLBI, NIA, NICHD, NC DHHS, BioKier, Roche Diagnostics; Consulting/advisory board for CSL-Behring, Medtronic, Beckman-Coulter, NHLBI; Non-funded “other” for BOD DHMRI, BOT AZ Healthcare Foundation.

Jacob Joseph reports research funding from NIH, Veterans Health Administration, Amgen, Kowa, and Alnylam.

Kenneth Schmader reports support from the Duke Pepper Older Americans Independence Center (NIA P30AG028716).

Michael Shapiro reports scientific advisory boards: Amgen, Novartis, NovoNordisk; Consulting: Ionis, Regeneron.

W. Schuyler Jones reports research grants from Bayer Boehringer Ingelheim, Merck, National Institutes of Health, Patient-Centered Outcomes Research Institute; Honoraria/Advisory Committees from Bayer, Bristol-Myers Squibb, Janssen Pharmaceuticals.

Catherine P. Benzinger reports site PI for studies funded by Department of Defense (WARRIOR), Amgen (VESALIUS), Novartis (INCLISIRAN), but are not relevant to the current study (does not receive financial support).

Raj C. Shah reports being the site principal investigator or sub-investigator for Alzheimer’s disease clinical trials for which his institution (Rush University Medical Center) is compensated (Amylyx Pharmaceuticals, Inc., Athira Pharma, Inc., Edgewater NEXT, Eli Lilly & Co., Inc., and Genentech, Inc.).

Christine E. Kistler reports serving as a consultant to a pharmacogenomics company, Base10, Inc. and on a pharmacogenomics advisory board for Baptist Health, FL.

Ariela R. Orkaby reports Veterans Affairs CSR&D CDA-2 award IK2-CX001800; consulting for Anthos Therapeutics.

Rowena J. Dolor reports grant funding from NIA paid to the institution for this project; PCORI, honorarium (less than $5000), as a member of the PCORI Clinical Trials Advisory Panel; Einstein-Montefiore, honorarium (less than $5000), as a member of their CTSA External Advisory Board; Veterans Administration, honorarium (less than $5000), as a consultant to the Women’s Health Practice-Based Research Network.

Karen P. Alexander reports grant funding from NIA to the institution for this project.

All other authors have nothing to report.

Figures

Figure 1.
Figure 1.
PREVENTABLE study design
Figure 2.
Figure 2.
PREVENTABLE pragmatism on PRECIS-2
See this image and copyright information in PMC

References

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