A Method to Quantify Mean Hypertension Treatment Daily Dose Intensity Using Health Care System Data

Min, Lillian; Ha, Jae Jung; Aubert, Carole E.; Hofer, Timothy P.; Sussman, Jeremy B.; Langa, Kenneth M.; Tinetti, Mary E.; Kim, Hyungjin Myra; Maciejewski, Matthew L.; Gillon, Leah; Chan, Chiao-Li; Kerr, Eve A.; Bravata, Dawn M.; Cushman, William C.

doi:10.1001/jamanetworkopen.2020.34059

Cited by 11 publications

(13 citation statements)

References 45 publications

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“…To capture antihypertensive treatment, we applied an algorithm that we previously validated in older Veterans, which uses VA and Medicare Part D pharmacy fills to determine the most likely antihypertensive medication on any day 24 . We standardized doses to HDDs, allowing comparison across medications 20 . We defined one HDD as half the maximum beneficial dose demonstrated in trials (Table S2), 25–27 and aggregated the standardized doses to obtain total dose.…”

Section: Methodsmentioning

confidence: 99%

“…The codes for the hypertension daily dose (HDD, see below) and fall injury have been published in open source format. 20,21…”

Section: Methodsmentioning

confidence: 99%

“…24 We standardized doses to HDDs, allowing comparison across medications. 20 We defined one HDD as half the maximum beneficial dose demonstrated in trials (Table S2), [25][26][27] and aggregated the standardized doses to obtain total dose. For example, hydrochlorothiazide 50 mg (maximal beneficial dose: 2 HDDs) with candesartan 16 mg (half maximal beneficial dose: 1 HDD) would equal 3 total HDDs.…”

Section: Variable Construction and Definitionmentioning

confidence: 99%

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Clinical outcomes of modifying hypertension treatment intensity in older adults treated to low blood pressure

Aubert

Kim

et al. 2021

J American Geriatrics Society

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Background/objectives: Hypertension treatment reduces cardiovascular events. However, uncertainty remains about benefits and harms of deintensification or further intensification of antihypertensive medication when systolic blood pressure (SBP) is tightly controlled in older multimorbid patients, because of their frequent exclusion in trials. We assessed the association of hypertension treatment deintensification or intensification with clinical outcomes in older adults with tightly controlled SBP. Design: Longitudinal cohort study (2011-2013) with 9-month follow-up. Setting: U.S.-nationwide primary care Veterans Health Administration healthcare system. Participants: Veterans aged 65 and older with baseline SBP <130 mmHg and ≥1 antihypertensive medication during ≥2 consecutive visits (N = 228,753).Exposure: Deintensification or intensification, compared with stable treatment. Main outcomes and measures: Cardiovascular events, syncope, or fall injury, as composite and distinct outcomes, within 9 months after exposure. Adjusted logistic regression and inverse probability of treatment weighting (IPTW, sensitivity analysis).

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Section: Methodsmentioning

confidence: 99%

“…The codes for the hypertension daily dose (HDD, see below) and fall injury have been published in open source format. 20,21…”

Section: Methodsmentioning

confidence: 99%

Section: Variable Construction and Definitionmentioning

confidence: 99%

See 1 more Smart Citation

Clinical outcomes of modifying hypertension treatment intensity in older adults treated to low blood pressure

Aubert

Kim

et al. 2021

J American Geriatrics Society

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“…To determine the complete antihypertensive medication regimen, we extracted data from both VA and Medicare Part D fills, and applied a measure that we previously validated in a sample of this Veterans population, which uses prefills (within 186 days before a visit) and refills (within 186 days after) to determine the most likely medication (name, class, dose) that a patient was receiving on any day (i.e., not only visit days) [ 5 ]. To allow comparison across all antihypertensive medications, we defined a standardized moderate daily dose (“Hypertension Daily Dose” [HDD]) for each medication, with one HDD corresponding to half the maximum beneficial dose demonstrated in hypertension trials, as published in the Joint National Commission (JNC) 7 and 8 and American Hospital Association/American College of Cardiology (AHA/ACC) guidelines [ [6] , [7] , [8] ].…”

Section: Methodsmentioning

confidence: 99%

“…In prior work focused on only those patients with aggressive hypertension treatment (systolic blood pressure [SBP] <120 mmHg and ≥3 antihypertensive medications), we developed a new measure to assess the intensity of hypertension pharmacological treatment (i.e., total daily dose) on any given day based on pharmacy fill data [ 4 , 5 ]. Unlike previous methods, this new measure uses standardized doses based on trial evidence-based beneficial doses used to treat hypertension.…”

Section: Introductionmentioning

confidence: 99%

Factors associated with antihypertensive treatment intensification and deintensification in older outpatients

Aubert

Kerr

et al. 2021

International Journal of Cardiology Hypertension

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Background New hypertension performance measures encourage more intensive treatment in older adults. Treatment intensification includes starting new medications and increasing the dose of old ones. Medication dose is particularly important to older adults, given their vulnerability to dose-related side effects. We previously validated a standardized measure of beneficial doses tested in hypertension trials, Hypertension Daily Dose (HDD). Aim of the study To test whether changes in treatment intensity using HDD was associated with systolic blood pressure (SBP) and patient characteristics. Methods Longitudinal study of all Veterans aged ≥65 years with a diagnosis of hypertension. We defined 3 groups of risk: 1) cardiovascular risk; 2) geriatric/frail; 3) low-risk (comparator). Using multinomial regression, we assessed the probability of deintensification, intensification, vs. stable treatment, according to SBP and group. Results Among 1,331,111 Veterans, 19.9% had deintensification, and 29.6% intensification. Deintensification decreased, while intensification increased, with SBP. Compared to low-risk patients, cardiovascular risk patients had 1.11 (95% CI 1.10–1.13) times the odds of intensifying, and geriatric/frail patients 1.45 (95%CI 1.43–1.47) times the odds of deintensifying. Discussion Patient-level HDD change was consistent with an expected association with cardiovascular risk and geriatric/frail conditions, suggesting that HDD can be used longitudinally to assess hypertension treatment modification in large health systems.

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Population‐based discovery and Mendelian randomization analysis identify telmisartan as a candidate medicine for Alzheimer's disease in African Americans

Zhang

Hou

et al. 2022

Alzheimer's & Dementia

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Introduction African Americans (AAs) and European Americans (EAs) differ in Alzheimer's disease (AD) prevalence, risk factors, and symptomatic presentation and AAs are less likely to enroll in AD clinical trials. Methods We conducted race‐conscious pharmacoepidemiologic studies of 5.62 million older individuals (age ≥60) to investigate the association of telmisartan exposure and AD outcome using Cox analysis, Kaplan–Meier analysis, and log‐rank test. We performed Mendelian randomization (MR) analysis of large ethnically diverse genetic data to test likely causal relationships between telmisartan's target and AD. Results We identified that moderate/high telmisartan exposure was significantly associated with a reduced incidence of AD in the AAs compared to low/no telmisartan exposure (hazard ratio [HR] = 0.77, 95% CI: 0.65–0.91, p‐value = 0.0022), but not in the non‐Hispanic EAs (HR = 0.97, 95% CI: 0.89–1.05, p‐value = 0.4110). Sensitivity and sex‐/age‐stratified patient subgroup analyses identified that telmisartan's medication possession ratio (MPR) and average hypertension daily dosage were significantly associated with a stronger reduction in the incidence of both AD and dementia in AAs. Using MR analysis from large genome‐wide association studies (GWAS) (over 2 million individuals) across AD, hypertension, and diabetes, we further identified AA‐specific beneficial effects of telmisartan for AD. Discussion Randomized controlled trials with ethnically diverse patient cohorts are warranted to establish causality and therapeutic outcomes of telmisartan and AD. Highlights Telmisartan is associated with lower risk of Alzheimer's disease (AD) in African Americans (AAs). Telmisartan is the only angiotensin II receptor blockers having PPAR‐γ agonistic properties with beneficial anti‐diabetic and renal function effects, which mitigate AD risk in AAs. Mendelian randomization (MR) analysis demonstrates the specificity of telmisartan's protective mechanism to AAs.

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A Method to Quantify Mean Hypertension Treatment Daily Dose Intensity Using Health Care System Data

Cited by 11 publications

References 45 publications

Clinical outcomes of modifying hypertension treatment intensity in older adults treated to low blood pressure

Clinical outcomes of modifying hypertension treatment intensity in older adults treated to low blood pressure

Factors associated with antihypertensive treatment intensification and deintensification in older outpatients

Population‐based discovery and Mendelian randomization analysis identify telmisartan as a candidate medicine for Alzheimer's disease in African Americans

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