Atorvastatin, Cardiovascular Events, and Disability-free Survival in Older Adults

RPR Commentary: Older patients with no history of CV disease who took a statin had fewer CV events but didn't live longer or have less disability. My conclusion is that statins should be used selectively in older people who are at increased risk of CV events. James W. Mold, MD, MPH

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Abstract
Background
The effectiveness and safety of statins for the primary prevention of cardiovascular events and the extension of disability-free survival among older adults remain uncertain.
Methods
We conducted a double-blind, randomized, placebo-controlled trial at general medical practices across Australia. Community-dwelling adults at least 70 years of age with no history of cardiovascular disease, diabetes, or dementia were randomly assigned in a 1:1 ratio to receive atorvastatin at a dose of 40 mg once daily or identical placebo. The two primary end points were a composite of death from cardiovascular causes, nonfatal myocardial infarction or stroke, or coronary revascularization (to assess effects on major cardiovascular events) and a composite of death from any cause, dementia, or persistent physical disability (to assess effects on disability-free survival). Analyses were performed according to a hierarchical testing plan.
Results
A total of 9971 participants were enrolled: 4984 were assigned to receive atorvastatin and 4987 to receive placebo. The mean (±SD) age of the participants was 74.7±4.5 years, and 51.9% were women. After a median of 5.9 years, a primary cardiovascular event had occurred in 297 participants (10.9 events per 1000 person-years) in the atorvastatin group and in 412 participants (15.5 events per 1000 person-years) in the placebo group (hazard ratio, 0.70; 95% confidence interval [CI], 0.61 to 0.82; P<0.001). Death from any cause, dementia, or persistent physical disability occurred in 637 participants (21.6 events per 1000 person-years) in the atorvastatin group and in 676 participants (23.0 events per 1000 person-years) in the placebo group (hazard ratio, 0.94; 95% CI, 0.84 to 1.05; P=0.25). Serious adverse events occurred in 131 participants (2.7%) in the atorvastatin group and in 129 (2.7%) in the placebo group, with musculoskeletal, hepatobiliary, and diabetes-related adverse events occurring more commonly in the atorvastatin group.
Conclusions
Treatment with atorvastatin led to a lower risk of major cardiovascular events than placebo at a median of 5.9 years but did not result in longer disability-free survival among community-dwelling older adults without clinical cardiovascular disease. (Funded by the National Health and Medical Research Council and others; STAREE ClinicalTrials.gov number, NCT02099123.)

Author/s:

Sophia Zoungas, Rory Wolfe, Chris Moran, Stephen J. Nicholls, Geoffrey C. Cloud, Christopher M. Reid, Andrew M. Tonkin, Lawrence Beilin, Anthony S. Wierzbicki, Trevor T.-J. Chong, Jonathan C. Broder, Andrea J. Curtis, Zachary Flanagan, Ingrid Hopper, Joanne Ryan, Simone Spark, John J. McNeil, Mark R. Nelson

Statins and cognitive decline in patients with Alzheimer's and mixed dementia: a longitudinal registry-based cohort study

Linda Fowler — Wed, 10 Jan 2024 14:41:05 +0000

Date Added:

January 10, 2024

Journal/Publication:

Alzheimer's Research & Therapy

Publisher:

BMC

Publication Date:

December 20, 2023

Issue:

220

Volume:

URL:

Statins and cognitive decline in patients with Alzheimer's and mixed dementia: a longitudinal registry-based cohort study

Type:

Clinical Research Results

Format:

Article

DOI (1):

10.1186/s13195-023-01360-0

Keywords

alzheimer's disease

Cholesterol metabolism

Cognitive impairment

cohort study

HMG-CoA reductase inhibitors

statins

PMID (1):

38115091

MeSH

Alzheimer Disease* / drug therapy

Atorvastatin / therapeutic use

Hydroxymethylglutaryl-CoA Reductase Inhibitors* / therapeutic use

Simvastatin / therapeutic use

cholesterol

cohort studies

Alzheimer Disease* / epidemiology

Humans

This cohort study of patients with dementia appears to show that statins seem to reduce the rate of progression of cognitive decline. That is certainly reassuring for those of us who have been concerned about whether we are depriving our brain cells of the cholesterol they require. James W. Mold, MD, MPH

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Background
Disturbances in brain cholesterol homeostasis may be involved in the pathogenesis of Alzheimer’s disease (AD). Lipid-lowering medications could interfere with neurodegenerative processes in AD through cholesterol metabolism or other mechanisms.

Objective
To explore the association between the use of lipid-lowering medications and cognitive decline over time in a cohort of patients with AD or mixed dementia with indication for lipid-lowering treatment.

Methods
A longitudinal cohort study using the Swedish Registry for Cognitive/Dementia Disorders, linked with other Swedish national registries. Cognitive trajectories evaluated with mini-mental state examination (MMSE) were compared between statin users and non-users, individual statin users, groups of statins and non-statin lipid-lowering medications using mixed-effect regression models with inverse probability of drop out weighting. A dose-response analysis included statin users compared to non-users.

Results
Our cohort consisted of 15,586 patients with mean age of 79.5 years at diagnosis and a majority of women (59.2 %). A dose-response effect was demonstrated: taking one defined daily dose of statins on average was associated with 0.63 more MMSE points after 3 years compared to no use of statins (95% CI: 0.33;0.94). Simvastatin users showed 1.01 more MMSE points (95% CI: 0.06;1.97) after 3 years compared to atorvastatin users. Younger (< 79.5 years at index date) simvastatin users had 0.80 more MMSE points compared to younger atorvastatin users (95% CI: 0.05;1.55) after 3 years. Simvastatin users had 1.03 more MMSE points (95% CI: 0.26;1.80) compared to rosuvastatin users after 3 years. No differences regarding statin lipophilicity were observed. The results of sensitivity analysis restricted to incident users were not consistent.

Conclusions
Some patients with AD or mixed dementia with indication for lipid-lowering medication may benefit cognitively from statin treatment; however, further research is needed to clarify the findings of sensitivity analyses

Author/s:

Bojana Petek, Henrike Häbel, Hong Xu, Marta Villa-Lopez, Irena Kalar, Minh Tuan Hoang, Silvia Maioli, Joana B Pereira, Shayan Mostafaei, Bengt Winblad, Milica Gregoric Kramberger, Maria Eriksdotter, Sara Garcia-Ptacek