Abstract
Background
Hyperlipidemia
and hypertension are modifiable risk factors for Alzheimer’s disease
and related dementias (ADRD). Approximately 25% of adults over age 65
use both antihypertensives (AHTs) and statins for these conditions.
While a growing body of evidence found statins and AHTs are
independently associated with lower ADRD risk, no evidence exists on
simultaneous use for different drug class combinations and ADRD risk.
Our primary objective was to compare ADRD risk associated with
concurrent use of different combinations of statins and
antihypertensives.
Methods
In
a retrospective cohort study (2007–2014), we analyzed 694,672 Medicare
beneficiaries in the United States (2,017,786 person-years) who
concurrently used both statins and AHTs. Using logistic regression
adjusting for age, socioeconomic status and comorbidities, we quantified
incident ADRD diagnosis associated with concurrent use of different
statin molecules (atorvastatin, pravastatin, rosuvastatin, and
simvastatin) and AHT drug classes (two renin-angiotensin system
(RAS)-acting AHTs, angiotensin converting enzyme inhibitors (ACEIs) or
angiotensin-II receptor blockers (ARBs), vs non-RAS-acting AHTs).
Findings
Pravastatin
or rosuvastatin combined with RAS-acting AHTs reduce risk of ADRD
relative to any statin combined with non-RAS-acting AHTs:
ACEI+pravastatin odds ratio (OR) = 0.942 (CI: 0.899–0.986, p = 0.011),
ACEI+rosuvastatin OR = 0.841 (CI: 0.794–0.892, p<0.001),
ARB+pravastatin OR = 0.794 (CI: 0.748–0.843, p<0.001),
ARB+rosuvastatin OR = 0.818 (CI: 0.765–0.874, p<0.001). ARBs combined
with atorvastatin and simvastatin are associated with smaller
reductions in risk, and ACEI with no risk reduction, compared to when
combined with pravastatin or rosuvastatin. Among Hispanics, no
combination of statins and RAS-acting AHTs reduces risk relative to
combinations of statins and non-RAS-acting AHTs. Among blacks using
ACEI+rosuvastatin, ADRD odds were 33% lower compared to blacks using
other statins combined with non-RAS-acting AHTs (OR = 0.672 (CI:
0.548–0.825, p<0.001)).
Conclusion
Among
older Americans, use of pravastatin and rosuvastatin to treat
hyperlipidemia is less common than use of simvastatin and atorvastatin,
however, in combination with RAS-acting AHTs, particularly ARBs, they
may be more effective at reducing risk of ADRD. The number of Americans
with ADRD may be reduced with drug treatments for vascular health that
also confer effects on ADRD.
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