Effect of initiation and continuous adherence to ARBs vs. ACEIs on risk of adjudicated mild cognitive impairment or dementia.

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 vs. ACEI on adjudicated amnestic mild cognitive impairment (MCI) and probable dementia (PD) in the Systolic Blood Pressure Intervention Trial. 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 non-adherent 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 vs. ACEI were 0.94 (95% CI: 0.66-1.29) and 0.79 (95% CI: 0.58-1.06). ARB vs. ACEI initiation and adherence was associated with a weighted RR of 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 vs. ACEI on adjudicated clinical cognitive outcomes.