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Observational Study
. 2022 Jul 1;5(7):e2220680.
doi: 10.1001/jamanetworkopen.2022.20680.

Risk of Mild Cognitive Impairment or Probable Dementia in New Users of Angiotensin II Receptor Blockers and Angiotensin-Converting Enzyme Inhibitors: A Secondary Analysis of Data From the Systolic Blood Pressure Intervention Trial (SPRINT)

Jordana B Cohen  1   2 , Zachary A Marcum  3 , Chong Zhang  4 , Catherine G Derington  5 , Tom H Greene  5 , Lama Ghazi  6 , Jennifer S Herrick  5   7 , Jordan B King  5   8 , Alfred K Cheung  9   10 , Nick Bryan  11 , Mark A Supiano  12 , Joshua A Sonnen  13 , William S Weintraub  14 , Daniel Scharfstein  4 , Jeff Williamson  15 , Nicholas M Pajewski  16 , Adam P Bress  5   7 ; Systolic Blood Pressure Intervention Trial (SPRINT) Research Group
Affiliations
Observational Study

Risk of Mild Cognitive Impairment or Probable Dementia in New Users of Angiotensin II Receptor Blockers and Angiotensin-Converting Enzyme Inhibitors: A Secondary Analysis of Data From the Systolic Blood Pressure Intervention Trial (SPRINT)

Jordana B Cohen et al. JAMA Netw Open. .

Abstract

Importance: The cardiovascular and renal outcomes of angiotensin-II receptor blocker (ARB) and angiotensin-converting enzyme inhibitor (ACEI) treatment are well-known; however, few studies have evaluated initiation of these agents and cognitive impairment.

Objective: To emulate a target trial to evaluate the cognitive outcomes of initiating an ARB- vs ACEI-based antihypertensive regimen in individuals at risk for mild cognitive impairment (MCI) and probable dementia (PD).

Design, setting, and participants: Active comparator, new-user observational cohort study design using data from the Systolic Blood Pressure Intervention Trial (SPRINT), conducted November 2010 through July 2018. Marginal cause-specific hazard ratios (HRs) and treatment-specific cumulative incidence functions were estimated with inverse probability (IP) weighting to account for confounding. Participants were using neither an ARB nor ACEI at baseline. Data analysis was conducted from April 7, 2021, to April 26, 2022.

Exposures: New users of ARB vs ACEI during the first 12 months of trial follow-up.

Main outcomes and measures: Composite of adjudicated amnestic MCI or PD.

Results: Of 9361 participants, 727 and 1313 new users of an ARB or ACEI, respectively, with well-balanced baseline characteristics between medication exposure groups after inverse probability weighting (mean [SD] age, 67 [9.5] years; 1291 ]63%] male; 240 [33%] Black; 89 [12%] Hispanic; 383 [53%] White; and 15 [2%] other race or ethnicity. In the primary analysis, during a median follow-up of 4.9 years, the inverse probability-weighted rate of amnestic MCI or PD was 4.3 vs 4.6 per 100 person-years among participants initiating ARB vs ACEI (HR, 0.93; 95% CI, 0.76-1.13). In subgroup analyses, new users of an ARB vs ACEI had a lower rate of amnestic MCI or PD among those in the standard systolic blood pressure treatment arm (HR, 0.61; 95% CI, 0.41-0.91) but not in the intensive arm (HR, 1.17; 95% CI, 0.90-1.52) (P = .007 for interaction).

Conclusions and relevance: In this observational cohort study of US adults at high cardiovascular disease risk, there was no difference in the rate of amnestic MCI or PD among new users of an ARB compared with ACEI, although 95% CIs were wide.

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Conflict of interest statement

Conflict of Interest Disclosures: Dr Cohen reported receiving grants from the National Institutes of Health (NIH) and the American Heart Association Bugher Award outside the submitted work. Dr Greene reported receiving grants from the NIH during the conduct of the study; personal fees from Durect Corp, Janssen Pharmaceuticals, and Pfizer Inc; and grants from Boehringer Ingelheim, AstraZeneca, and CSL outside the submitted work. Dr Cheung reported receiving grants from the NIH and was an investigator of the main SPRINT trial. Dr Bryan reported receiving grants from the NIH during the conduct of the study. Dr Supiano reported receiving grants from the NIH outside the submitted work. Dr Scharfstein reported receiving grants from the NIH during the conduct of the study. Dr Pajewski reported receiving grants from the National Institute on Aging (NIA) during the conduct of the study. Dr Bress reported receiving grants from the NIA during the conduct of the study. No other disclosures were reported.

Figures

Figure 1.
Figure 1.. Cumulative Incidence of Amnestic Mild Cognitive Impairment or Probable Dementia and All-Cause Death Among New Users of an ARB- vs ACEI-Based Antihypertensive Medication Regimen Before and After IP Weighting
Shown are the treatment-specific cumulative incidence functions for the primary outcome (a composite of amnestic MCI or probable dementia) in the unweighted (A) and inverse-probability weighted analysis (B). Numbers at risk are omitted because the cumulative incidence curves were generated from a model using weighted samples. ACEI indicates angiotensin-converting enzyme inhibitor; ARB, angiotensin II receptor blocker; IP, inverse probability; MCI, mild cognitive impairment.
Figure 2.
Figure 2.. IP-Weighted Primary Outcome Results in Subgroups Among New Users of an ARB- vs ACEI-Based Antihypertensive Medication Regimen
For statistical purposes, race and ethnicity subgroups were categorized as binary. The Not Black category comprises Hispanic, White, and other race and ethnicity categories. ACEI indicates angiotensin-converting enzyme inhibitor; ARB, angiotensin-II receptor blocker; IP, inverse probability; MCI, mild cognitive impairment. aUnadjudicated. Based on race-and education-specific Montreal Cognitive Assessment thresholds.
See this image and copyright information in PMC

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