Target trial emulation using cohort studies: estimating the effect of antihypertensive medication initiation on incident dementia

Authors

Erin E. Bennett, Department of Epidemiology, Milken Institute School of Public Health, The George Washington University, Washington, DC, USA.
Chelsea Liu, Department of Epidemiology, Milken Institute School of Public Health, The George Washington University, Washington, DC, USA.
Emma K. Stapp, Department of Epidemiology, Milken Institute School of Public Health, The George Washington University, Washington, DC, USA.
Kan Z. Gianattasio, Department of Health Care Evaluation, NORC at the University of Chicago, Bethesda, MD, USA.
Scott C. Zimmerman, Department of Epidemiology and Biostatistics, University of California at San Francisco, San Francisco, CA, USA.
Jingkai Wei, Department of Epidemiology and Biostatistics, Arnold School of Public Health, University of South Carolina, Columbia, SC, USA.
Michael E. Griswold, Memory Impairment and Neurodegenerative Dementia Center, University of Mississippi Medical Center, Jackson, MS, USA.
Annette L. Fitzpatrick, Department of Family Medicine, School of Medicine, University of Washington, Seattle, WA, USA.
Rebecca F. Gottesman, National Institute of Neurological Disorders and Stroke, Bethesda, MD, USA.
Lenore J. Launer, Laboratory of Epidemiology and Population Sciences, National Institute of Aging, Bethesda, MD, USA.
B Gwen Windham, Memory Impairment and Neurodegenerative Dementia Center, University of Mississippi Medical Center, Jackson, MS, USA.
Deborah A. Levine, Department of Internal Medicine, School of Medicine, University of Michigan, Ann Arbor, MI, USA.
Alison E. Fohner, Department of Epidemiology, School of Public Health, University of Washington, Seattle, WA, USA.
M Maria Glymour, Department of Epidemiology and Biostatistics, University of California at San Francisco, San Francisco, CA, USA.
Melinda C. Power, Department of Epidemiology, Milken Institute School of Public Health, The George Washington University, Washington, DC, USA.

Document Type

Journal Article

Publication Date

10-1-2024

Journal

Epidemiology (Cambridge, Mass.)

DOI

10.1097/EDE.0000000000001802

Abstract

BACKGROUND: Observational studies link high midlife systolic blood pressure to increased dementia risk. However, synthesis of evidence from randomized controlled trials has not definitively demonstrated that antihypertensive medication use reduces dementia risk. Here, we emulate target trials of antihypertensive medication initiation on incident dementia using three cohort studies, with attention to potential violations of necessary assumptions. METHODS: We emulated trials of antihypertensive medication initiation on incident dementia using data from the Atherosclerosis Risk in Communities (ARIC) study, Cardiovascular Health Study (CHS), and Health and Retirement Study (HRS). We used data-driven methods to restrict participants to initiators and non-initiators with overlap in propensity scores and positive control outcomes to look for violations of positivity and exchangeability assumptions. RESULTS: Analyses were limited by the small number of cohort participants who met eligibility criteria. Associations between antihypertensive medication initiation and incident dementia were inconsistent and imprecise (ARIC: HR = 0.30 [0.05, 1.93]; CHS: HR = 0.66 [0.27, 1.64]; HRS: HR = 1.09 [0.75, 1.59]). More stringent propensity score restriction had little effect on findings. Sensitivity analyses using a positive control outcome unexpectedly suggested antihypertensive medication initiation increased risk of coronary heart disease in all three samples. CONCLUSIONS: Positive control outcome analyses suggested substantial residual confounding in effect estimates from our target trials, precluding conclusions about the impact of antihypertensive medication initiation on dementia risk through target trial emulation. Formalized processes for identifying violations of necessary assumptions will strengthen confidence in target trial emulation and avoid inappropriate confidence in emulated trial results.

APA Citation

Bennett, Erin E.; Liu, Chelsea; Stapp, Emma K.; Gianattasio, Kan Z.; Zimmerman, Scott C.; Wei, Jingkai; Griswold, Michael E.; Fitzpatrick, Annette L.; Gottesman, Rebecca F.; Launer, Lenore J.; Windham, B Gwen; Levine, Deborah A.; Fohner, Alison E.; Glymour, M Maria; and Power, Melinda C., "Target trial emulation using cohort studies: estimating the effect of antihypertensive medication initiation on incident dementia" (2024). GW Authored Works. Paper 5898.
https://hsrc.himmelfarb.gwu.edu/gwhpubs/5898

Department

Epidemiology