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- Title
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).
- Authors
Cohen, Jordana B.; Marcum, Zachary A.; Zhang, Chong; Derington, Catherine G.; Greene, Tom H.; Ghazi, Lama; Herrick, Jennifer S.; King, Jordan B.; Cheung, Alfred K.; Bryan, Nick; Supiano, Mark A.; Sonnen, Joshua A.; Weintraub, William S.; Scharfstein, Daniel; Williamson, Jeff; Pajewski, Nicholas M.; Bress, Adam P.
- Abstract
Key Points: Question: Is initiation of angiotensin II receptor blockers (ARBs), compared with angiotensin-converting enzyme inhibitors (ACEIs), associated with a reduced risk of cognitive impairment, after controlling for potential pretreatment confounders? Findings: This active-comparator, new-user design cohort study identified 2040 new users of ACEIs/ARBs from the Systolic Blood Pressure Intervention Trial (SPRINT). The overall risk of cognitive impairment was not appreciably different between new users of an ARB vs ACEI. Meaning: The findings of this study suggest that pragmatic trials reflective of blood pressure management outside the clinical trial setting are warranted to further elucidate cognitive outcomes with ARBs vs ACEIs initiation. 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. This cohort study examines the rates of mild cognitive impairment and probable dementia among initiators of an angiotensin II receptor blocker (ARB) vs angiotensin-converting enzyme inhibitor (ACEI)–based antihypertensive medication regimen.
- Subjects
RISK factors of mild cognitive impairment; DEMENTIA risk factors; SCIENTIFIC observation; CONFIDENCE intervals; ACE inhibitors; RISK assessment; DESCRIPTIVE statistics; ANGIOTENSIN receptors; ODDS ratio; SECONDARY analysis; LONGITUDINAL method
- Publication
JAMA Network Open, 2022, Vol 5, Issue 7, pe2220680
- ISSN
2574-3805
- Publication type
Article
- DOI
10.1001/jamanetworkopen.2022.20680