I guess you'll have to ask your competent? doctor. Lower mortality risk, but higher hospitalization risk! A conundrum for your doctor to interpret.
Do Statins Really Raise Vascular Hospitalization Risk in Dementia?
Statin use has been linked to higher rates of cardiovascular or cerebrovascular hospitalization in older adults with dementia, results of a large observational study suggest.
However, small event numbers and several limitations warrant cautious interpretation, the researchers note. With this in mind, the investigators, led by Sonia Lech, PhD, Department of Psychiatry and Neurosciences, Charité-Universitätsmedizin, Berlin, Germany, recommend that clinicians consider individualized risk–benefit assessment when considering statin use in this patient population.
This finding was also unexpected. In earlier research using the same nursing home cohort, the investigators found that statin use in residents with dementia was associated with significantly lower mortality — a contrast they note in their paper.
The findings ran counter to the group’s original hypothesis. Their prior study, published in February 2024, showed a 20% reduction in all-cause mortality among statin users with dementia, the authors noted, yet the current analysis did not show a corresponding reduction in cardiovascular or cerebrovascular hospitalizations.
“This suggests that while statins may contribute to a reduction in mortality risk, they do not necessarily translate into a reduced rate of hospitalizations due to cardiovascular and cerebrovascular events” in this population, they write. The study was published online November 17 in the journal Stroke.
Research Gap
Statins are well established for primary and secondary prevention of cardiovascular and cerebrovascular disease, but evidence for their benefit in people with dementia has been lacking, even though cardiovascular and cerebrovascular disease are major causes of morbidity and mortality in this population.
“There is currently no research published evaluating the effect of statin use in [people with dementia] on cardiovascular and cerebrovascular outcomes; thus, there is a lack of evidence to support guidelines for the care of [people with dementia],” the investigators note.
In an effort to fill this knowledge gap, the investigators examined statin use and a potential link to hospitalization due to these events among nursing home residents with and without dementia.
The researchers analyzed insurance claims from 96,162 nursing home residents in Germany, including 58,900 people with dementia (mean age, 83.4 years; 69.8% female) and 37,262 without dementia (mean age, 82.2 years; 66.9% female). Participants were further categorized as statin users or nonusers before outcomes were compared.
The study’s primary outcome was hospitalization due to cardiovascular or cerebrovascular disease events. Researchers adjusted for age, sex, care level, cardiovascular disease, cerebrovascular disease, other medical and psychiatric conditions, comorbidities, medications, and number of hospital admissions.
During an average observation period of 2.3 years, there were 4528 hospitalizations among individuals with dementia. Of these, 2621 occurred in those using statins.
In this group of individuals, statin use was associated with an increased risk for hospitalization compared with nonuse (hazard ratio [HR] 1.06; 95% CI, 1.01-1.12; P = .023).
Frailty a Factor?
This elevated risk suggests statins “may increase the cerebrovascular and neurodegenerative pathological processes in the already vulnerable brain of patients with dementia,” the investigators write.
Such patients, they add, “may represent an inherently frail survivor population” who “might be more susceptible to complications or comorbidities that necessitate hospitalization.”
The possibility that frailty rather than statin use explains the increased risk for hospitalization can’t entirely be ruled out, they noted.
Moderate- and high-intensity statin use was associated with a higher risk for hospitalization compared with nonuse (HR, 1.15; 95% CI, 1.07-1.23; P < .001 for moderate-intensity statins; and HR, 1.55; 95% CI, 1.15-2.10; P = .005 for high-intensity statins). Notably, there was no such association with low-intensity statin use.
Among residents with dementia and no history of atherosclerotic cardiovascular disease (ASCVD), statin use was also linked to an increased risk for hospitalization (HR, 1.30; 95% CI, 1.12-1.52; P < .001), a pattern not observed in those with prior ASCVD.
The risk for hospitalization was also higher among individuals newly prescribed statins compared with nonusers. However, in sensitivity analyses, applying an 18-month exposure lag substantially reduced this association.
In the group without dementia, there were 2450 hospitalizations due to cardiovascular and cerebrovascular events during an average observation period of 2.0 years. Of these, 1431 events occurred among statin users.
Compared with statin nonusers, the only significant associations between statin use and hospitalization in this group were seen with high-intensity statins (P = .029) and with newly prescribed statins (P < .001). However, as in the dementia cohort, sensitivity analyses showed that applying a lagged exposure window attenuated these risks.
Potential Limitations
Because statins are often prescribed for secondary prevention after events such as myocardial infarction or stroke, patients who receive them may already be at higher baseline risk for subsequent events, a pattern that can lead to reverse causation bias, the authors noted.
They noted that the use of cardiovascular medications such as diuretics, nitrates, and alpha-receptor blockers did not change the results. They also pointed out that antipsychotic medication use — known to increase cardiovascular and cerebrovascular risk — could not account for the differences between those with and without dementia, as usage rates of antipsychotic meds were similar in both groups.
The study’s limitations include the relatively small number of cardiovascular and cerebrovascular events, which may have reduced the statistical power of the analyses, and the results could be influenced by factors unrelated to statin use, such as differences in access to care or in preferences around hospitalization.
In addition, dementia diagnoses were drawn from administrative codes rather than clinical adjudication, raising the possibility of misclassification. In addition, the investigators had no information on dementia severity — a key determinant of hospitalization risk. These gaps, they noted, limit the extent to which the findings can be interpreted as reflecting true differences in event risk.
They note that more research is needed before any definitive conclusions can be drawn but add that the findings warrant “cautious consideration of statin use in people with dementia.”
The study was funded by Siftung Charité as part of the Berlin Institute of Health (BIH) visiting professorship grant to author Sevil Yasar, PhD, MD, Division of Geriatric Medicine and Gerontology, Johns Hopkins University, Baltimore, MD. The authors report no relevant financial relationships.
