BACKGROUND:Initial combination therapy has been recommended for patients with high blood pressure (BP). We evaluated annual trends in initial combination therapy and post-treatment BP in Kaiser Permanente Southern California, an integrated healthcare system that adopted combination therapy in 2005. METHODS:This serial cross-sectional study included patients newly initiating antihypertensive therapy from 2008 to 2024. We calculated annual age- and sex-standardized proportion of patients initiating combination therapy. Prevalence ratios (PR) of achieving post-treatment BP <140/90 and <130/80 mm Hg between 6 and 12 months were estimated for initial combination versus monotherapy adjusting for demographic and pre-treatment BP. RESULTS:Among 221,384 patients, the use of initial combination therapy increased from 39% in 2008 to 45% in 2011 (p-trend=0.009), then decreased to 27% in 2024 (p-trend <0.001). The decreasing trend of initial combination therapy from 2011 to 2024 was consistent across all pre-treatment systolic BP levels: 130-139 mm Hg (33% to 20%), 140-149 mm Hg (42% to 22%), 150-159 mm Hg (49% to 29%), and ≥160 mm Hg (61% to 36%). Post-treatment BP <140/90 mm Hg was 75% in 2011 and 66% in 2024; BP <130/80 mm Hg was 35% in 2011 and 25% in 2024. PRs for initial combination versus monotherapy were 1.09 (95% CI 1.08, 1.10) for post-treatment BP <140/90 mm Hg and 1.31 (95% CI 1.29, 1.33) for <130/80 mm Hg. CONCLUSIONS:Although initial combination therapy remains associated with improved BP control, its use has declined in recent years, underscoring the importance of sustained support for guideline concordant care.

BACKGROUND:Hypertension is a modifiable risk factor for dementia, yet the comparative effectiveness of angiotensin receptor blockers (ARBs) versus angiotensin converting enzyme inhibitors (ACEIs) on dementia risk remains uncertain. OBJECTIVE:To compare the risk of dementia and dementia-free death of ARB versus ACEI initiation among US Veterans with incident hypertension. METHODS:We conducted a retrospective target trial emulation using a new-user, active-comparator design among Veterans with incident hypertension. We analyzed longitudinal electronic health records from 2,577,000 individuals who initiated ARBs or ACEIs between 1/1/2000-12/31/2017, with up to five years of follow-up. The exposure was initiation of an ARB-based versus ACEI-based antihypertensive regimen. Co-primary outcomes were dementia, identified using natural language processing of clinical notes, and dementia-free death. We used inverse probability of treatment weights based on 66 pretreatment covariates to estimate the cumulative incidence of the outcomes for each treatment group. Weighted risk ratios and absolute risk differences through five years were computed with bootstrapped 95% CIs. Secondary outcomes included all-cause death and a composite of dementia or death, evaluated using a weighted Kaplan-Meier approach. RESULTS:Among 2,577,000 Veterans (mean age, 63 years; 4.5% female; 65% White; 15% Black), 10% initiated ARBs and 90% initiated ACEIs. Over five years of follow up, 6% developed dementia, 12% died without dementia, and 13% died overall. ARB initiation yielded consistently lower risk of dementia (risk ratio, 0.88; 95% CI, 0.83-0.93 at 6 months to 0.92; 95% CI, 0.90-0.94 at 5 years) and dementia-free death (risk ratio, 0.90; 95% CI, 0.86-0.96 at 6 months to 1.00; 95% CI, 0.98-1.01 at 5 years) than ACEI initiation. Effects on secondary outcomes were similar to those for primary outcomes. Greater protective dementia effects were observed in older and male Veterans and non-statin users, with similar effects on dementia-free death. DISCUSSION:Among US Veterans with incident treated hypertension, initiation of ARB versus ACEI antihypertensive regimen conveyed a modestly lower risk of dementia. Given the high prevalence of hypertension, these modest effects may confer meaningful population-level benefits on brain health. Future research estimating per-protocol effects using a more generalizable population is needed to confirm our findings. KEY WORDS:antihypertensive medication, dementia, natural language processing, target trial emulation, Veteran.

In this cross-sectional study of 5.8 million US adults with hypertension taking antihypertensive single-pill combination (SPC) products in the Medical Expenditure Panel Survey (2016-2022), the median out-of-pocket cost was $5.53 per SPC fill (interquartile range [IQR] $0.00-$12.70). A hypothetical small (e.g., $4/30 days) cost cap could reduce annual out-of-pocket spending by $152.9 million overall (median savings $5.35 (IQR $1.06-$12.81) per fill). A hypothetical large cost cap (e.g., $11/30 days) could reduce annual out-of-pocket spending by $61.2 million overall (median savings $2.27 (IQR $0.00-$11.28) per fill). Despite relatively low out-of-pocket costs, these spending reductions may lower patient financial burdens associated with antihypertensive SPC therapy.

Abstract Background: The comparative long-term effects of initiation of an angiotensin receptor blocker (ARB) and angiotensin-converting enzyme inhibitor (ACEI) on cancer risk remain uncertain. The objective of this study was to compare risks of cancer and non-cancer mortality between ARB and ACEI initiators among US veterans. Methods: This prospective cohort included 2,658,758 veterans with hypertension and no history of cancer who initiated either an ARB or an ACEI within the Veterans Health Administration between January 1, 2000, and December 31, 2017. Participants were followed from treatment initiation until the first occurrence of an outcome, death, loss to follow-up, or December 31, 2022 (the end of study). Initiation of ARB or ACEI treatment was determined from pharmacy dispensing records, excluding those with a history of cancer or who filled ARB or ACEI before the study period. The index date (baseline) was defined as the date of initiating either treatment. Inverse probability (IP) of treatment weighting was applied to adjust for 27 baseline covariates and estimate the intent-to-treat effect of ARB versus ACEI initiation. The co-primary outcomes were time to any cancer (ascertained from the VA Cancer Registry) and non-cancer mortality. Secondary outcomes included all-cause mortality, the composite of any cancer or death, incidence of specific cancers, and non-cancer-specific mortality. Cumulative incidence functions and risk ratios (RRs) with 95% confidence intervals (95% CI) were calculated using IP-weighted Aalen-Johansen estimator in the competing risks setting. Results: Among 2,658,758 veterans (median follow-up, 10 years; mean age, 63 years; 5% women; 76% non-Hispanic White; 15% Black), 90% initiated ACEIs and 10% initiated ARBs. ARB initiation was associated with a lower 10-year risk of any cancer (RR, 0.79; 95% CI, 0.75-0.83) and a similar 10-year risk of non-cancer mortality (RR, 1.03; 95% CI, 0.88-1.07) compared with ACEI initiation. Associations were consistent across most cancer types, except for inconclusive findings for breast and renal cancers. In subgroup analyses, a stronger inverse association between ARB initiation compared to ACEI initiation and cancer risk was observed among older patients (≥70 years). Conclusions and Relevance: ARB initiators had a lower risk of developing any cancer compared with initiation of ACEIs, with no observed difference in non-cancer or all-cause mortality. We also reported stronger inverse association for ARBs in older adults in subgroup analyses. Further research should clarify underlying biological mechanisms, confirm causality in randomized trials, and evaluate personalized antihypertensive strategies that incorporate cancer risk considerations. Citation Format: Caroline Himbert, Daniel K. Addo, Yizhe Xu, Tao He, Catherine G. Derington, Tom Greene, Jordana B. Cohen, Adam Bress, Sheetal Hardikar. Cancer risk with initiation of angiotensin receptor blockers (ARBs) vs. angiotensin converting enzyme inhibitors (ACEIs) [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 1 (Regular Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(7 Suppl):Abstract nr 1304.

Hypertension is a leading cause of cardiovascular disease and disproportionately affects African American (AA) adults. Apparent treatment-resistant hypertension (aTRH) is highly prevalent in this population. Sodium intake is associated with blood pressure (BP) levels, yet the relationship between sodium and the risk of developing aTRH in AA adults remains unclear. This study examined the association between 24-hour urinary sodium excretion and incident aTRH among AA adults with hypertension, using data from the Jackson Heart Study (JHS). The JHS included 5306 self-identified AA adults from Jackson, Mississippi, with data collected from 2000 to 2013. This analysis included 452 participants with baseline hypertension and complete urinary excretion and medication data. Sodium excretion was categorized into quartiles: Q1 (253 to 2530 mg/day), Q2 (2553 to 3657 mg/day), Q3 (3680 to 4692 mg/day), and Q4 (4715 to 9775 mg/day). A semi-parametric proportional hazards model was used to determine the association between sodium excretion and incident aTRH. Participants had a mean age of 63 years, and 27.7% were men. Over a median follow-up of 7.5 years, 123 participants (27.2%) developed aTRH. The incidence of aTRH was 25.7%, 24.8%, 29.2%, and 29.2% in Q1, Q2, Q3, and Q4 of urinary sodium excretion, respectively. In adjusted models, there was no significant association between urinary sodium excretion and incident aTRH [HRs (95% CIs): Q2 = 0.71 (0.34, 1.46), Q3 = 1.02 (0.50, 2.06), Q4 = 0.95 (0.46, 2.00); P = 0.166]. Among AA adults with treated hypertension, sodium intake, as measured by 24-hour urinary sodium excretion, was not significantly associated with incident resistant hypertension.

BACKGROUND:Amid persistently low blood pressure (BP) control rates and pervasive therapeutic inertia, we evaluated trends in pre- and posttreatment BP before and after 2 major disruptions (the 2017 target‑lowering guideline and the COVID‑19 pandemic) to assess their impact on early hypertension management. METHODS:This retrospective cohort study of national Veterans Health Administration data included outpatient adults newly diagnosed with hypertension and starting antihypertensive medication between November 13, 2014, and May 31, 2023 (index date). Patients were stratified into 3 periods corresponding to preguideline/prepandemic (Period 1), postguideline/prepandemic (Period 2), and postguideline/postpandemic (Period 3), and into 3 pretreatment systolic BP (SBP) groups based on the average of ≥2 measurements in the 90-day preindex period (<140, 140-160, or ≥160 mm Hg). Across periods, multivariable analyses evaluated: (1) mean posttreatment SBP (mean of measurements from days 180-365 postindex); and (2) posttreatment BP control (<140/90 or <130/80 mm Hg). RESULTS:Among 271 496 Veterans (mean age, 62 years; 92% male; 66% non-Hispanic White), 39%, 32%, and 29% were in Periods 1, 2, and 3, respectively. Adjusted posttreatment SBP across periods was 128, 135, and 142 mm Hg for the <140, 140 to 160, and ≥160 groups, respectively. Rates of posttreatment BP control <140/90 mm Hg across Periods 1, 2, and 3, respectively, were 82.3%, 83.3%, and 84.2% (SBP <140 group); 64.1%, 66.1%, and 67.3% (140-160 group); and 46.4%, 47.0%, and 48.6% (≥160 group). For BP control <130/80 mm Hg, rates were 38.2%, 40.0%, and 39.9% (SBP <140 group); 20.7%, 22.0%, and 22.6% (140-160 group); and 15.1%, 15.4%, and 15.2% (≥160 group). CONCLUSIONS:Despite the target-lowering guideline and the care-disrupting pandemic, BP levels and control among Veterans remained largely unchanged. At 1 year, only half to two-thirds achieved BP <140/90 mm Hg, and few reached <130/80 mm Hg, underscoring persistent clinical inertia and the need to improve early hypertension management in the Veterans Health Administration.

Importance:Timely prescription of quadruple guideline-directed medical therapies (GDMTs) for patients with heart failure with reduced ejection fraction (HFrEF) is associated with improved morbidity and mortality, yet contemporary estimates of time to quadruple therapy (TTQ) and the factors associated with its achievement remain unknown. Objective:To characterize TTQ and factors associated with TTQ in HFrEF. Design, Setting, and Participants:This was a retrospective cohort study including patients with incident HFrEF from the Veterans Health Administration database during the January 1, 2020, to December 31, 2023, period. Study data were analyzed from November 2024 to December 2025. Exposures:Primary factors included race and ethnicity, sex, and copay status (priority group). Secondary factors included clinical characteristics. Main Outcomes and Measures:The main outcome included quadruple therapy according to pharmacy fill data-concurrent use of evidence-based β-blockers, renin-angiotensin system inhibitors, mineralocorticoid receptor antagonists, and sodium-glucose cotransporter-2 inhibitors. TTQ was defined as the first date that all 4 medication classes overlapped, based on dispense date and days' supply. Results:Among 52 850 patients with incident HFrEF (median [SD] age, 71.8 [11] years; 51 473 male [97%]; 10 791 Black [20%]; 2528 Hispanic [5%]; 35 867 White [68%]; 3664 other [7%]), 11 217 (21.2%) achieved quadruple therapy over a median (IQR) follow-up of 2.9 (1.9-3.9) years. The median (IQR) TTQ was 197 (49-528) days. After adjustment, Black patients (hazard ratio [HR], 1.22; 95% CI, 1.15-1.30), Hispanic patients (HR, 1.21; 95% CI, 1.09-1.33), and those from other racial or ethnic groups (HR, 1.11; 95% CI, 1.02-1.20) had higher rates of quadruple therapy than White patients. There was no difference in TTQ in females vs males (HR, 0.97; 95% CI, 0.86-1.09). Prescription copays (priority groups 2-8) were associated with an 8% lower rate of achieving quadruple therapy (HR, 0.92; 95% CI, 0.87-0.96) than no prescription copay (priority group 1). Rates of quadruple therapy were higher among veterans with an outpatient HFrEF diagnosis vs inpatient (22.2% vs 14.2%), with diabetes vs without diabetes (23.6% vs 19.3%), and without chronic kidney disease vs with chronic kidney disease (22.5% vs 18.1%). Conclusion and Relevance:Results of this cohort study suggest that opportunities exist to improve both the rate and timeliness of quadruple therapy as only 21.2% of patients with HFrEF achieved it, with a median follow-up of 2.9 years and TTQ of 6 months. Medication copays represent a modifiable barrier, providing a potential target for interventions to enhance TTQ.

Hypertension is a leading cause of cardiovascular morbidity and mortality. Individuals living in rural areas have a higher prevalence of hypertension and a lower prevalence of blood pressure control. Factors contributing to the increased hypertension prevalence in rural populations include shortages of health care professionals, limited access to transportation and longer travel distances to care, lower health literacy, socioeconomic factors, and reduced access to pharmacies. Approaches to addressing barriers to effective hypertension management include expanding rural telehealth services, deploying mobile units, leveraging pharmacists, implementing remote blood pressure monitoring, and engaging community health workers. Health services need to be culturally tailored and address the unique challenges faced by rural communities. Further research is needed to identify effective methods for addressing health disparities experienced by rural populations related to hypertension management.

KEY POINTS:In veterans with type 2 diabetes and low kidney failure risk, sodium-glucose cotransporter 2 inhibitors (SGLT2is) were more kidney protective while glucagon-like peptide-1 receptor agonists (GLP-1 RAs) were more cardioprotective. For cardiovascular-kidney-metabolic outcomes, GLP-1 RAs were more protective at moderate kidney failure risk and SGLT2is were more protective at high kidney failure risk. The kidney failure risk equation might be a clinically useful tool to guide therapy in type 2 diabetes. BACKGROUND:Head-to-head comparisons of non-exendin glucagon-like peptide-1 receptor agonists (GLP-1 RAs) and sodium-glucose cotransporter 2 inhibitors (SGLT2is) on kidney failure or cardiovascular-kidney-metabolic (CKM) composite end points are lacking. Whether kidney failure risk modifies the comparative effectiveness of GLP-1 RA versus SGLT2i is clinically relevant. METHODS:We defined a national veterans cohort with type 2 diabetes who initiated an SGLT2i, non-exendin GLP-1 RA, or insulin glargine between January 1, 2018, and December 31, 2021. After applying inverse probability of treatment weighting to balance baseline characteristics, outcomes were compared across new-user groups through March 31, 2023. Outcomes included kidney failure (stage 5 CKD or long-term KRT), major adverse cardiovascular events (MACEs: heart failure, myocardial infarction, or stroke), CKM composite (kidney failure or MACE), all-cause death, and composites of outcomes with death. We tested for effect modification by the kidney failure risk equation (KFRE) score on comparative pairwise drug effectiveness. RESULTS:Out of 160,428 veterans, 53%, 14%, and 34% were new users of SGLT2i, GLP-1 RA, and insulin glargine, respectively. Relative to GLP-1 RA new-users, SGLT2i new-users had similar mortality risk, a trend toward lower kidney failure risk (hazard ratio [HR], 0.89; 95% confidence interval [CI], 0.74 to 1.06), but higher risk of MACE (HR, 1.14; 95% CI, 1.09 to 1.20) and CKM composite (HR, 1.13; 95% CI, 1.08 to 1.19). The effect of SGLT2i versus GLP-1 RA differed significantly between moderate-risk (2%-6%) and high-risk (≥6%) KFRE subgroups for all outcomes except all-cause death. In those with moderate-risk KFRE, GLP-1 RA seemed more protective for kidney failure, MACE, and CKM composite, while SGLT2i appeared more protective in those with high-risk KFRE. CONCLUSIONS:Compared with GLP-1 RA, SGLT2i had comparable risks of mortality, perhaps a lower risk of kidney failure, but modestly higher risk of cardiovascular events in the entire cohort. However, GLP-1 RA were more beneficial in those with moderate kidney failure risk and SGLT2i more beneficial in those with high kidney failure risk. PODCAST:This article contains a podcast at https://dts.podtrac.com/redirect.mp3//www.asn-online.org/media/podcast/JASN/2026_07_29_KTS_July2026.mp3.

Atrial fibrillation (AF) is increasing in incidence, prevalence, and lifetime risk, and contributes to substantially greater health care costs and increased risks of stroke, heart failure, and mortality. Improving adherence to evidence-based recommendations equitably in AF is critical to advancing clinical care, patient outcomes, and public health. The writing committee developed a comprehensive set of 5 performance measures, which are appropriate for public reporting or pay-for-performance programs, and 16 quality measures, which are useful to clinicians and health care organizations for quality improvement. The writing committee selected the measures from the strongest recommendations (Class 1 or 3) in the “2023 ACC/AHA/ACCP/HRS Guideline for the Diagnosis and Management of Atrial Fibrillation.” The purpose of the writing committee’s performance measures is meant to ensure that patients with newly diagnosed AF receive a basic clinical evaluation, with an emphasis on secondary prevention for patients at all stages of AF, documenting stroke risk, and, if indicated, providing appropriate anticoagulation. AF quality measures cover a variety of topics including measuring and addressing health inequities, optimizing antiarrhythmic or anticoagulant treatment, engaging in shared decision-making for rate- versus rhythm-control strategies, and, in appropriate patients, offering catheter ablation for those with heart failure with reduced ejection fraction. The performance and quality measures are intended to advance the quality and equity of AF care across all patient populations with AF.

Background Blood pressure (BP) control remains suboptimal in the United States despite available low‐cost antihypertensive medications. Even small out‐of‐pocket medication costs may contribute to adherence. We determined whether $0 versus >$0 out‐of‐pocket costs for antihypertensive medications is associated with differences in adherence, discontinuation, BP control, and cardiovascular outcomes. Methods We included veterans with newly diagnosed hypertension who initiated antihypertensive medication in the Veterans Health Administration from 2004 to 2022. A fuzzy regression discontinuity design with 2‐stage residual inclusion leveraged differences in medication copay policy at a 50% service‐connected disability threshold (≥50% service‐connected disability: $0 out‐of‐pocket cost versus <50%: $8 monthly cost). Outcomes included 1‐year medication nonadherence (proportion of days covered <80%), 1‐year medication discontinuation (no medication in the final 90 days of the study year), 1‐year BP control (systolic BP/diastolic BP <140/90 mm Hg and <130/80 mm Hg) and cardiovascular disease events (myocardial infarction, coronary revascularization, peripheral artery disease, or stroke). Results Among 417 705 veterans (mean±SD age, 56 [13] years; 92% male; 61% non‐Hispanic White), 296 432 (71%) had $0 out‐of‐pocket costs. Accounting for changes in eligibility for $0 copays at the 50% service‐related disability threshold, $0 out‐of‐pocket costs were associated with lower odds of nonadherence (odds ratio [OR], 0.87 [95% CI, 0.81–0.94]) and medication discontinuation (OR, 0.77 [95% CI, 0.71–0.84]). One‐year BP control <140/90 mm Hg or <130/80 mm Hg and cardiovascular disease events events were similar between groups. Conclusions Among veterans with newly diagnosed hypertension, modest out‐of‐pocket medication costs were associated with lower adherence and discontinuation. These findings can inform ongoing discussions regarding policy levers for improving hypertension outcomes.

BackgroundCardiovascular (CV) disease and its risk factors such as hypertension, diabetes, and hyperlipidemia account for most chronic diseases experienced by adults in the US. The use of text-based "behavioral nudges" supports behavior change and self-management of chronic disease. Building upon our previous trial utilizing an artificially intelligent (AI) chatbot for medication adherence, the Chat for Heart Health randomized controlled trial aims to test the comparative effectiveness of 3 text-based methods of delivering "nudges" to change health behaviors to reduce cardiovascular disease risk in patients across 3 safety-net healthcare systems.MethodsAdult patients ages 18-89 with CV risk factors will be recruited from 3 health systems. A target of 2097 participants will be randomized to 3 study arms: generic text messaging, AI interactive chatbot messaging, and AI interactive chatbot messaging plus pharmacist support. Evaluation of the intervention and the program will be carried out using the RE-AIM and PRISM frameworks. The primary effectiveness outcome is the change in CV risk reduction behaviors as defined by the American Heart Association's Life's Essential 8 score. Secondary outcomes including patient self-efficacy scores, clinical events, healthcare utilization, and facilitators and barriers to implementation and adoption will also be assessed.DiscussionOur large-scale pragmatic trial engages with patients and health systems who have traditionally not engaged in research, which presented substantial challenges yet will make our results more generalizable to diverse populations. Additionally, we engaged a diverse advisory panel made up of patients, community members, providers, and health systems leaders throughout the study to ensure sociocultural, linguistic, and community relevance. The results of this trial (if the intervention is effective) could lead to broader dissemination of a low-cost intervention to support behavior change to reduce CV risk.Trial registrationNCT06324981 (3/14/2024), https://clinicaltrials.gov/study/NCT06324981

AIMS:To compare the risk of all-cause death and cardiovascular events in new users of insulin glargine, glucagon-like peptide-1 receptor agonists (GLP-1RA) and sodium-glucose cotransporter-2 inhibitors (SGLT2i), particularly in subgroups defined by baseline haemoglobin A1C (HbA1C), body mass index (BMI) and estimated glomerular filtration rate (eGFR). MATERIALS AND METHODS:We conducted an active comparator, new user design study in a national cohort of 161 405 veterans with type 2 diabetes (T2D) on metformin and initiated insulin glargine (n = 54 375), GLP-1RA (n = 22 145) or SGLT2i (n = 84 885) between 1 January 2018 and 31 December 2021. Patients were followed until 31 March 2023. Inverse probability weighted Cox regression models were used for treatment comparisons on all-cause deaths and cardiovascular events in the entire cohort and above subgroups. RESULTS:There were 20 788 cardiovascular events/414 414 person-years and 15 268 all-cause deaths/446 458 person-years. Insulin glargine had a higher hazard of all-cause death compared to GLP-1RA (hazard ratio [HR] 1.57, 95% confidence interval [CI] 1.48-1.67) or SGLT2i (HR 1.55, 95% CI 1.48-1.61) in the entire cohort and across subgroups, especially in those with HbA1C levels <9.0%. Results were similar for secondary outcomes. Compared to GLP-1RA, SGLT2i had similar risk of all-cause death (HR 1.03, 95% CI 0.97-1.10) but higher hazard of cardiovascular events (HR 1.13, 95% CI 1.08-1.19). Across subgroups, GLP-1RA and SGLT2i had generally similar effects, with SGLT2i showing a slightly higher risk in some cases. CONCLUSIONS:Insulin glargine might be deleterious particularly in those with HbA1C <9.0%. There was no clear evidence for prioritization of SGLT2i versus GLP-1RA across subgroups.