TY - JOUR
T1 - Risk of Mild Cognitive Impairment or Probable Dementia in New Users of Angiotensin II Receptor Blockers and Angiotensin-Converting Enzyme Inhibitors
T2 - A Secondary Analysis of Data from the Systolic Blood Pressure Intervention Trial (SPRINT)
AU - Cohen, Jordana B.
AU - Marcum, Zachary A.
AU - Zhang, Chong
AU - Derington, Catherine G.
AU - Greene, Tom H.
AU - Ghazi, Lama
AU - Herrick, Jennifer S.
AU - King, Jordan B.
AU - Cheung, Alfred K.
AU - Bryan, Nick
AU - Supiano, Mark A.
AU - Sonnen, Joshua A.
AU - Weintraub, William S.
AU - Scharfstein, Daniel
AU - Williamson, Jeff
AU - Pajewski, Nicholas M.
AU - Bress, Adam P.
N1 - Funding Information:
Administrative, technical, or material support: Marcum, Derington, Bryan, Williamson, Bress. Supervision: Marcum, Bryan, Scharfstein, Pajewski, Bress. 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
Funding Information:
Funding/Support: This project was directly supported by NIA grant R01G065805. Dr Marcum was supported by grant K76AG059929 from the NIA. Dr Cohen is supported by grants K23-HL133843, R01-HL153646, R01-HL157108, and U01-HL160277 from the National Heart, Lung, and Blood Institute; grant U01TR003734 from the National Center for Advancing Translational Sciences; grants R01DK123104 and U24DK060990 from the National Institute of Diabetes and Digestive and Kidney Diseases; and an American Heart Association Bugher Award. The Systolic Blood Pressure Intervention Trial was funded by the National Heart, Lung, and Blood Institute; the National Institute of Diabetes and Digestive and Kidney Diseases; the NIA; and the National Institute of Neurological Disorders and Stroke under contracts HHSN268200900040C, HHSN268200900046C, HHSN268200900047C, HHSN268200900048C, and HHSN268200900049C and interagency agreement A-HL-13-002-001. The trial was also supported in part with resources and use of facilities through the Department of Veterans Affairs. Additional support was provided by the National Institute of General Medical Sciences and Centers of Biomedical Research Excellence award NIGMS P30GM103337 (awarded to Tulane University) and through the following National Center for Advancing Translational Sciences clinical and translational science awards: UL1TR000439 (awarded to Case Western Reserve University); UL1RR025755 (Ohio State University); UL1RR024134 and UL1TR000003 (University of Pennsylvania); UL1RR025771 (Boston University); UL1TR000093 (Stanford University); UL1RR025752, UL1TR000073, and UL1TR001064 (Tufts University); UL1TR000050 (University of Illinois); UL1TR000005 (University of Pittsburgh); 9U54TR000017-06 (University of Texas Southwestern Medical Center); UL1TR000105-05 (University of Utah); UL1 TR000445 (Vanderbilt University); UL1TR000075 (George Washington University); UL1 TR000002 (University of California, Davis); UL1 TR000064 (University of Florida); and UL1TR000433 (University of Michigan).
Publisher Copyright:
© 2022 American Medical Association. All rights reserved.
PY - 2022/7/14
Y1 - 2022/7/14
N2 - 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.
AB - 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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U2 - 10.1001/jamanetworkopen.2022.20680
DO - 10.1001/jamanetworkopen.2022.20680
M3 - Article
C2 - 35834254
AN - SCOPUS:85134432826
SN - 2574-3805
VL - 5
SP - E2220680
JO - JAMA network open
JF - JAMA network open
IS - 7
ER -