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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).
JAMA Netw Open. 2022 Jul 01; 5(7):e2220680.JN

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.

Authors+Show Affiliations

Department of Medicine, Renal-Electrolyte and Hypertension Division, Perelman School of Medicine, University of Pennsylvania, Philadelphia. Department of Biostatistics, Epidemiology, and Informatics, Perelman School of Medicine, University of Pennsylvania, Philadelphia.Department of Pharmacy, University of Washington School of Pharmacy, Seattle.Intermountain Healthcare Department of Population Health Sciences, Division of Biostatistics, Spencer Fox Eccles School of Medicine, University of Utah, Salt Lake City.Intermountain Healthcare Department of Population Health Sciences, Division of Health System Innovation and Research, Spencer Fox Eccles School of Medicine, University of Utah, Salt Lake City.Intermountain Healthcare Department of Population Health Sciences, Division of Health System Innovation and Research, Spencer Fox Eccles School of Medicine, University of Utah, Salt Lake City.Clinical and Translational Research Accelerator, Yale University School of Medicine, New Haven, Connecticut.Intermountain Healthcare Department of Population Health Sciences, Division of Health System Innovation and Research, Spencer Fox Eccles School of Medicine, University of Utah, Salt Lake City. George E. Wahlen Department of Veterans Affairs Medical Center, Salt Lake City, Utah.Intermountain Healthcare Department of Population Health Sciences, Division of Health System Innovation and Research, Spencer Fox Eccles School of Medicine, University of Utah, Salt Lake City. Institute for Health Research, Kaiser Permanente Colorado, Aurora.Department of Internal Medicine, Spencer Fox Eccles School of Medicine, University of Utah, Salt Lake City. Medical Service, Veterans Affairs Salt Lake City Healthcare System, Salt Lake City, Utah.Department of Radiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia.Geriatrics Division, Spencer Fox Eccles School of Medicine, University of Utah, Salt Lake City.Departments of Pathology, Neurology, and Neurosurgery, McGill University, Montréal, Québec, Canada.MedStar Health Research Institute and Georgetown University, Washington, DC.Intermountain Healthcare Department of Population Health Sciences, Division of Biostatistics, Spencer Fox Eccles School of Medicine, University of Utah, Salt Lake City.Sticht Center for Healthy Aging and Alzheimer's Prevention, Wake Forest University School of Medicine, Winston-Salem, North Carolina.Department of Biostatistics and Data Science, Wake Forest University School of Medicine, Winston-Salem, North Carolina.Intermountain Healthcare Department of Population Health Sciences, Division of Health System Innovation and Research, Spencer Fox Eccles School of Medicine, University of Utah, Salt Lake City. George E. Wahlen Department of Veterans Affairs Medical Center, Salt Lake City, Utah.No affiliation info available

Pub Type(s)

Journal Article
Observational Study
Research Support, N.I.H., Extramural

Language

eng

PubMed ID

35834254

Citation

Cohen, Jordana B., et al. "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)." JAMA Network Open, vol. 5, no. 7, 2022, pp. e2220680.
Cohen JB, Marcum ZA, Zhang C, et al. 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). JAMA Netw Open. 2022;5(7):e2220680.
Cohen, J. B., Marcum, Z. A., Zhang, C., Derington, C. G., Greene, T. H., Ghazi, L., Herrick, J. S., King, J. B., Cheung, A. K., Bryan, N., Supiano, M. A., Sonnen, J. A., Weintraub, W. S., Scharfstein, D., Williamson, J., Pajewski, N. M., & Bress, A. P. (2022). 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). JAMA Network Open, 5(7), e2220680. https://doi.org/10.1001/jamanetworkopen.2022.20680
Cohen JB, et al. 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). JAMA Netw Open. 2022 Jul 1;5(7):e2220680. PubMed PMID: 35834254.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - 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). 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, AU - ,, Y1 - 2022/07/01/ PY - 2022/7/14/entrez PY - 2022/7/15/pubmed PY - 2022/7/19/medline SP - e2220680 EP - e2220680 JF - JAMA network open JO - JAMA Netw Open VL - 5 IS - 7 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. SN - 2574-3805 UR - https://www.unboundmedicine.com/medline/citation/35834254/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__ DB - PRIME DP - Unbound Medicine ER -