#41

Another massive study testing atorvastatin in older adults for healthspan!

The recruiting PREVENTABLE study, where 20,000 older adults above age of 75 is randomized to 40 mg atorvastatin or placebo.

Atorvastatin, and all statin medications, do more than just lower cholesterol. These drugs also reduce inflammation and they may help prevent memory loss, improve physical function, and even prevent cancer.

Lipid levels are most useful to help understand an individual’s long-term health risk to
prevent heart disease, but you have already lived past age 75 without heart disease. Congratulations!

From the FAQ (2022)

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So two massive trials are expected to be done for atorvastatin at 40 mg in older adults: STAREE and PREVENTABLE.

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.

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J American Geriatrics Society - 2023 - Joseph - Pragmatic evaluation of events and benefits of lipid lowering in older.pdf (1.7 MB)

PREVENTABLE will be the largest trial conducted in adults ≥75 years in the United States and is tailored to answer key clinical questions while limiting participant burden

Results will establish whether initiating a high-intensity statin is effective in lengthening health span in older patients without heart disease or dementia

First proven healthspan increasing drug in humans is atorvastatin? What’s the chance for this? It seems high.

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Statins [often used to reduce rapamycin-increased LDL] inhibit coenzyme Q10 AND GGP/MK4 AND dolichol AND N-linked glycosylation (+ other negative effects)
#42

I love it - well done! Its this kind of thing that I find really helpful at this site. People making the extra effort to get access to the good new data!

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#43

Great but results in 2027 only: ClinicalTrials.gov

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#44

For now, we don’t know whether statins prevent dementia but we know with a high likelihood that they are a net benefit based on all cause mortality data. It is promising two large trials, and the largest trial ever done in older adults in the U.S, and for dementia prevention, has chosen high-intensity atorvastatin for investigation. Is that a signal meanwhile for a very good risk. vs. reward calculation?

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#45

It just signals that researchers seem to think that atorvastatin is the best statin for dementia prevention. But atorvastatin failed in the previous trial I mentioned. So wait and see.

#46

Two of four groups used atorvastatin in that study and in combination with other drugs so you don’t know what is causing what. It isn’t surprising either because of the relative few participants it couldn’t detect neither harm nor benefit if I understand it correctly in the time period of the study.

#47

I hurt a finger a little bit some while after switching to atorvastatin, is it possible it could affect the tendons in some way (especially in comparison to rosuvastatin)? It felt like something in the knuckle of a finger snapped a bit. It has gotten better over time. Never had a problem like that before, and it felt so random. So I’ll try Crestor 5 mg for awhile again. I might switch back to atorvastatin later, but to be honest I am not so worried about the diabetes risk etc which I can monitor.

@DeStrider I think you have mentioned some study that had to do with something like this at some point.

#48

My tendons have been weak either way so I might’ve been predisposed for my finger to go visit snap city. Exercise most likely helps with this.

Statin treatment increases the clinical risk of tendinopathy through matrix metalloproteinase release – a cohort study design combined with an experimental study

https://www.nature.com/articles/s41598-019-53238-7

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#49

Comparative Effectiveness and Safety of Atorvastatin Versus Rosuvastatin: A Multi-database Cohort Study 2024

Among the 285 680 eligible participants in both databases, 6-year all-cause mortality was lower for rosuvastatin than for atorvastatin (2.57 vs. 2.83 per 100 person-years in the CRDS database and 0.66 vs. 0.90 per 100 person-years in the UKB database), with differences in cumulative incidence of −1.03% (95% CI, −1.44% to −0.46%) in the CRDS database and −1.38% (CI, −2.50% to −0.21%) in the UKB database. For secondary outcomes in both databases, rosuvastatin conferred lower risks for major adverse cardiovascular events and major adverse liver outcomes. In the UKB database, the risk for development of type 2 diabetes mellitus was higher with rosuvastatin, and the 2 medications carried similar risks for development of chronic kidney disease and other statin-related adverse effects.

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#50

Very interesting. Where the lipid levels (hopefully ApoB or non-HDL Cholesterol) similar in the 2 groups or did the rosuvastatin group have lower levels? Did they match people to compare atorvastatin vs. rosuvastatin with similar lipid levels with outcomes? Without doing that, we’d not be able to conclude either agent is better or worse.

#51

I don’t have access to the full paper but I assume they did that. (“Cox proportional hazards regressions were used after 1:1 multilevel propensity score matching.”)

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#52

Since ACM was mentioned, a result for many statins, but in diabetics. Pitavastatin looking good:

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