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Randomized Controlled Trial
. 2025 Jun 10;80(7):glaf028.
doi: 10.1093/gerona/glaf028.

Effect of Initiation and Continuous Adherence to ARBs Versus ACEIs on Risk of Adjudicated Mild Cognitive Impairment or Dementia

Catherine G Derington  1 , Ransmond O Berchie  1 , Daniel O Scharfstein  1 , Ryan M Andrews  2 , Tom H Greene  1 , Yizhe Xu  1 , Jordan B King  1   3 , Mark A Supiano  4   5 , Joshua A Sonnen  6 , Jeff Williamson  7 , Nicholas M Pajewski  8 , Jeremy J Pruzin  9 , Jordana B Cohen  10   11 , Adam P Bress  1   12
Affiliations
Randomized Controlled Trial

Effect of Initiation and Continuous Adherence to ARBs Versus ACEIs on Risk of Adjudicated Mild Cognitive Impairment or Dementia

Catherine G Derington et al. J Gerontol A Biol Sci Med Sci. .

Abstract

Background: Whether the differing mechanistic effects between angiotensin-2 receptor blockers (ARBs) and angiotensin-converting enzyme inhibitors (ACEIs) on the renin-angiotensin system translate to differential effects on clinical cognitive outcomes is unclear.

Methods: We employed an active comparator, new-user cohort study to emulate a target trial evaluating the per-protocol effect of initiating and continuously adhering to an ARB versus ACEI on adjudicated amnestic mild cognitive impairment (MCI) and probable dementia (PD) in the Systolic Blood Pressure Intervention Trial (SPRINT). Inverse probability of treatment and censoring weighted cumulative incidence functions accounted for confounding, the competing risk of death, adherence, and loss to follow-up.

Results: Of 9,361 SPRINT participants (mean age 67.1 ± 9.5 years, 36.7% female, 58.7% non-Hispanic White), 710 and 1,289 were new users of an ARB or ACEI. Overall, 291 (41.0%) ARB initiators and 854 (66.3%) ACEI initiators were nonadherent during follow-up. The IP-weighted 4-year probabilities of full adherence and being alive among ARB was 56.0% (95% CI: 52.2%-59.9%) and 30.5% (95% CI: 28.0%-33.1%) for ACEI. The 4-year weighted risk ratios (RR) for amnestic MCI/PD and for amnestic MCI/PD/death with initiation and full adherence to ARB versus ACEI were 0.94 (95% CI: 0.66-1.29) and 0.79 (95% CI: 0.58-1.06). The weighted 4-year weighted RR for all-cause death with ARB versus ACEI initiation and adherence was 0.36 (95% CI: 0.14-0.76).

Conclusions: In this target trial emulation of older adults at high risk for cardiovascular disease, there was insufficient evidence to conclude a beneficial effect of initiating and continuously adhering to an ARB versus ACEI on adjudicated clinical cognitive outcomes.

Keywords: Antihypertensive; Cognition; Hypertension; Medication; Treatment.

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Conflict of interest statement

None.

Figures

Figure 1.
Figure 1.
Causal adherence plot estimating the probability of full adherence and being alive by a follow-up month in a scenario without censoring under the two treatments. Abbreviations: ACEI = angiotensin-converting enzyme inhibitor; ARB = angiotensin-II receptor blocker..
Figure 2.
Figure 2.
IP-weighted risk curves for the primary composite outcome of amnestic MCI or probable dementia comparing continuous use of ARB vs. ACEI in SPRINT. Abbreviations: ACEI = angiotensin-converting enzyme inhibitor; ARB= angiotensin-II receptor blocker; MCI = mild cognitive impairment; PD = probable dementia; RR = risk ratio; SPRINT = Systolic Blood Pressure Intervention Trial.
See this image and copyright information in PMC

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