Association Between Young Adult Characteristics and Blood Pressure Trajectories.

BACKGROUND: Blood pressure (BP) trajectories from young adulthood through middle age are associated with cardiovascular risk. We examined the associations of hypertension risk factors with BP trajectories among a large diverse sample. METHODS AND RESULTS: We analyzed data from young adults, aged 18 to 39 years, with untreated BP <140/90 mm Hg at baseline from Kaiser Permanente Southern California (N=355 324). We used latent growth curve models to identify 10-year BP trajectories and to assess the associations between characteristics in young adulthood and BP trajectories. We identified the following 5 distinct systolic BP trajectories, which appeared to be determined mainly by the baseline BP with progressively higher BP at each year: group 1 (lowest BP trajectory, 7.9%), group 2 (26.5%), group 3 (33.0%), group 4 (25.4%), and group 5 (highest BP trajectory, 7.3%). Older age (adjusted odds ratio for 30-39 versus 18-29 years, 1.23 [95% CI, 1.18-1.28]), male sex (13.38 [95% CI, 12.80-13.99]), obesity (body mass index ≥30 versus 18.5-24.9 kg/m2, 14.81 [95% CI, 14.03-15.64]), overweight (body mass index 25-29.9 versus 18.5-24.9 kg/m2, 3.16 [95% CI, 3.00-3.33]), current smoking (1.58 [95% CI, 1.48-1.67]), prediabetes (1.21 [95% CI, 1.13-1.29]), diabetes (1.60 [95% CI, 1.41-1.81]) and high low-density lipoprotein cholesterol (≥160 versus <100 mg/dL, 1.52 [95% CI, 1.37-1.68]) were associated with the highest BP trajectory (group 5) compared with the reference group (group 2). CONCLUSIONS: Traditional hypertension risk factors including smoking, diabetes, and elevated lipids were associated with BP trajectories in young adults, with obesity having the strongest association with the highest BP trajectory group.

Cost of Cardiovascular Disease Event and Cardiovascular Disease Treatment-Related Complication Hospitalizations in the United States.

BACKGROUND: Cardiovascular disease (CVD) is among the costliest conditions in the United States, and cost-effectiveness analyses can be used to assess economic impact and prioritize CVD treatments. We aimed to develop standardized, nationally representative CVD events and selected possible CVD treatment-related complication hospitalization costs for use in cost-effectiveness analyses. METHODS: Nationally representative costs were derived using publicly available inpatient hospital discharge data from the 2012-2018 National Inpatient Sample. Events were identified using the principal International Classification of Diseases, Ninth Revision and International Classification of Diseases, Tenth Revision codes. Facility charges were converted to costs using charge-to-cost ratios, and total costs were estimated by applying a published professional fee ratio. All costs are reported in 2021 US dollars. Mean costs were estimated for events overall and stratified by age, sex, and survival status at discharge. Annual costs to the US health care system were estimated by multiplying the mean annual number of events by the mean total cost per discharge. RESULTS: The annual mean number of hospital discharges among CVD events was the highest for heart failure (1 087 000 per year) and cerebrovascular disease (800 600 per year). The mean cost per hospital discharge was the highest for peripheral vascular disease ($33 700 [95% CI, $33 300-$34 000]) and ventricular tachycardia/ventricular fibrillation ($32 500 [95% CI, $32 100-$32 900]). Hospitalizations contributing the most to annual US health care costs were heart failure ($19 500 [95% CI, $19 300-$19 800] million) and acute myocardial infarction ($18 300, [95% CI, $18 200-$18 500] million). Acute kidney injury was the most frequent possible treatment complication (515 000 per year), and bradycardia had the highest mean hospitalization costs ($17 400 [95% CI, $17 200-$17 500]). CONCLUSIONS: The hospitalization cost estimates and statistical code reported in the current study have the potential to increase transparency and comparability of cost-effectiveness analyses for CVD in the United States.

Familial Hypercholesterolemia Variant and Cardiovascular Risk in Individuals With Elevated Cholesterol.

Importance: Familial hypercholesterolemia (FH) is a genetic disorder that often results in severely high low-density lipoprotein cholesterol (LDL-C) and high risk of premature coronary heart disease (CHD). However, the impact of FH variants on CHD risk among individuals with moderately elevated LDL-C is not well quantified. Objective: To assess CHD risk associated with FH variants among individuals with moderately (130-189 mg/dL) and severely (≥190 mg/dL) elevated LDL-C and to quantify excess CHD deaths attributable to FH variants in US adults. Design, Setting, and Participants: A total of 21 426 individuals without preexisting CHD from 6 US cohort studies (Atherosclerosis Risk in Communities study, Coronary Artery Risk Development in Young Adults study, Cardiovascular Health Study, Framingham Heart Study Offspring cohort, Jackson Heart Study, and Multi-Ethnic Study of Atherosclerosis) were included, 63 of whom had an FH variant. Data were collected from 1971 to 2018, and the median (IQR) follow-up was 18 (13-28) years. Data were analyzed from March to May 2023. Exposures: LDL-C, cumulative past LDL-C, FH variant status. Main Outcomes and Measures: Cox proportional hazards models estimated associations between FH variants and incident CHD. The Cardiovascular Disease Policy Model projected excess CHD deaths associated with FH variants in US adults. Results: Of the 21 426 individuals without preexisting CHD (mean [SD] age 52.1 [15.5] years; 12 041 [56.2%] female), an FH variant was found in 22 individuals with moderately elevated LDL-C (0.3%) and in 33 individuals with severely elevated LDL-C (2.5%). The adjusted hazard ratios for incident CHD comparing those with and without FH variants were 2.9 (95% CI, 1.4-6.0) and 2.6 (95% CI, 1.4-4.9) among individuals with moderately and severely elevated LDL-C, respectively. The association between FH variants and CHD was slightly attenuated when further adjusting for baseline LDL-C level, whereas the association was no longer statistically significant after adjusting for cumulative past LDL-C exposure. Among US adults 20 years and older with no history of CHD and LDL-C 130 mg/dL or higher, more than 417 000 carry an FH variant and were projected to experience more than 12 000 excess CHD deaths in those with moderately elevated LDL-C and 15 000 in those with severely elevated LDL-C compared with individuals without an FH variant. Conclusions and Relevance: In this pooled cohort study, the presence of FH variants was associated with a 2-fold higher CHD risk, even when LDL-C was only moderately elevated. The increased CHD risk appeared to be largely explained by the higher cumulative LDL-C exposure in individuals with an FH variant compared to those without. Further research is needed to assess the value of adding genetic testing to traditional phenotypic FH screening.

Effectiveness of Hypertension Management Strategies in SPRINT-Eligible US Adults: A Simulation Study.

BACKGROUND: Despite reducing cardiovascular disease (CVD) events and death in SPRINT (Systolic Blood Pressure Intervention Trial), intensive systolic blood pressure goals have not been adopted in the United States. This study aimed to simulate the potential long-term impact of 4 hypertension management strategies in SPRINT-eligible US adults. METHODS AND RESULTS: The validated Blood Pressure Control-Cardiovascular Disease Policy Model, a discrete event simulation of hypertension care processes (ie, visit frequency, blood pressure [BP] measurement accuracy, medication intensification, and medication adherence) and CVD outcomes, was populated with 25 000 SPRINT-eligible US adults. Four hypertension management strategies were simulated: (1) usual care targeting BP <140/90 mm Hg (Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure usual care), (2) intensive care per the SPRINT protocol targeting BP <120/90 mm Hg (SPRINT intensive), (3) usual care targeting guideline-recommended BP <130/80 mm Hg (American College of Cardiology/American Heart Association usual care), and (4) team-based care added to usual care and targeting BP <130/80 mm Hg. Relative to the Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure usual care, among the 18.1 million SPRINT-eligible US adults, an estimated 138 100 total CVD events could be prevented per year with SPRINT intensive, 33 900 with American College of Cardiology/American Heart Association usual care, and 89 100 with team-based care. Compared with the Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure usual care, SPRINT intensive care was projected to increase treatment-related serious adverse events by 77 600 per year, American College of Cardiology/American Heart Association usual care by 33 300, and team-based care by 27 200. CONCLUSIONS: As BP control has declined in recent years, health systems must prioritize hypertension management and invest in effective strategies. Adding team-based care to usual care may be a pragmatic way to manage risk in this high-CVD-risk population.

Cost-Effectiveness of Icosapent Ethyl in REDUCE-IT USA: Results From Patients Randomized in the United States.

BACKGROUND: In 3146 REDUCE-IT USA (Reduction of Cardiovascular Events With Icosapent Ethyl Intervention Trial USA) participants, icosapent ethyl (IPE) reduced first and total cardiovascular events by 31% and 36%, respectively, over 4.9 years of follow-up. METHODS AND RESULTS: We used participant-level data from REDUCE-IT USA, 2021 US costs, and IPE costs ranging from $4.59 to $11.48 per day, allowing us to examine a range of possible medication costs. The in-trial analysis was participant-level, whereas the lifetime analysis used a Markov model. Both analyses considered value from a US health sector perspective. The incremental cost-effectiveness ratio (incremental costs divided by incremental quality-adjusted life-years) of IPE compared with standard care (SC) was the primary outcome measure. There was incremental gain in quality-adjusted life-years with IPE compared with SC using in-trial (3.28 versus 3.13) and lifetime (10.36 versus 9.83) horizons. Using an IPE cost of $4.59 per day, health care costs were lower with IPE compared with SC for both in-trial ($29 420 versus $30 947) and lifetime ($216 243 versus $219 212) analyses. IPE versus SC was a dominant strategy in trial and over the lifetime, with 99.7% lifetime probability of an incremental cost-effectiveness ratio <$50 000 per quality-adjusted life-year gained. At a medication cost of $11.48 per day, the cost per quality-adjusted life-year gained was $36 208 in trial and $9582 over the lifetime. CONCLUSIONS: In this analysis, at $4.59 per day, IPE offers better outcomes than SC at lower costs in trial and over a lifetime and is cost-effective at $11.48 per day for conventional willingness-to-pay thresholds. Treatment with IPE should be strongly considered in US patients like those enrolled in REDUCE-IT USA. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT01492361.

Cost-Effectiveness of Pharmacotherapy for the Treatment of Obesity in Adolescents.

Importance: Antiobesity pharmacotherapy is recommended for adolescents ages 12 years and older with obesity. Several medications have been approved by the US Food and Drug Administration for adolescent use, but the most cost-effective medication remains unclear. Objective: To estimate the cost-effectiveness of lifestyle counseling alone and as adjunct to liraglutide, mid-dose phentermine and topiramate (7.5 mg phentermine and 46 mg topiramate), top-dose phentermine and topiramate (15 mg phentermine and 92 mg topiramate), or semaglutide among adolescent patients with obesity. Design, Setting, and Participants: This economic evaluation used a microsimulation model to project health and cost outcomes of lifestyle counseling alone and adjunct to liraglutide, mid-dose phentermine and topiramate, top-dose phentermine and topiramate, or semaglutide over 13 months, 2 years, and 5 years among a hypothetical cohort of 100 000 adolescents with obesity, defined as an initial body mass index (BMI; calculated as weight in kilograms divided by height in meters squared) of 37. Model inputs were derived from clinical trials, published literature, and national sources. Data were analyzed from April 2022 to July 2023. Exposures: Lifestyle counseling alone and as adjunct to liraglutide, mid-dose phentermine and topiramate, top-dose phentermine and topiramate, or semaglutide. Main Outcomes and Measures: The main outcome was quality-adjusted life years (QALYs), costs (2022 US dollars), and incremental cost-effectiveness ratios (ICERs), with future costs and QALYs discounted 3.0% annually. A strategy was considered cost-effective if the ICER was less than $100 000 per QALY gained. The preferred strategy was determined as the strategy with the greatest increase in QALYs while being cost-effective. One-way and probabilistic sensitivity analyses were used to assess parameter uncertainty. Results: The model simulated 100 000 adolescents at age 15 with an initial BMI of 37, of whom 58 000 (58%) were female. At 13 months and 2 years, lifestyle counseling was estimated to be the preferred strategy. At 5 years, top-dose phentermine and topiramate was projected to be the preferred strategy with an ICER of $56 876 per QALY gained vs lifestyle counseling. Semaglutide was projected to yield the most QALYs, but with an unfavorable ICER of $1.1 million per QALY gained compared with top-dose phentermine and topiramate. Model results were most sensitive to utility of weight reduction and weight loss of lifestyle counseling and top-dose phentermine and topiramate. Conclusions and Relevance: In this economic evaluation of pharmacotherapy for adolescents with obesity, top-dose phentermine and topiramate as adjunct to lifestyle counseling was estimated to be cost-effective after 5 years. Long-term clinical trials in adolescents are needed to fully evaluate the outcomes of pharmacotherapy, especially into adulthood.

Estimated Population Health Benefits of Intensive Systolic Blood Pressure Treatment Among SPRINT-Eligible US Adults.

BACKGROUND: The Systolic Blood Pressure Intervention Trial (SPRINT) demonstrated an intensive (<120 mm Hg) vs. standard (<140 mm Hg) systolic blood pressure (SBP) goal lowered cardiovascular disease (CVD) risk. Estimating the effect of intensive SBP lowering among SPRINT-eligible adults most likely to benefit can guide implementation efforts. METHODS: We studied SPRINT participants and SPRINT-eligible participants in the Reasons for Geographic and Racial Differences in Stroke (REGARDS) Study and National Health and Nutrition Examination Surveys (NHANES). A published algorithm of predicted CVD benefit with intensive SBP treatment was used to categorize participants into low, medium, or high predicted benefit. CVD event rates were estimated with intensive and standard treatment. RESULTS: Median age was 67.0, 72.0, and 64.0 years in SPRINT, SPRINT-eligible REGARDS, and SPRINT-eligible NHANES participants, respectively. The proportion with high predicted benefit was 33.0% in SPRINT, 39.0% in SPRINT-eligible REGARDS, and 23.5% in SPRINT-eligible NHANES. The estimated difference in CVD event rate (standard minus intensive) was 7.0 (95% confidence interval [CI] 3.4-10.7), 8.4 (95% CI 8.2-8.5), and 6.1 (95% CI 5.9-6.3) per 1,000 person-years in SPRINT, SPRINT-eligible REGARDS participants, and SPRINT-eligible NHANES participants, respectively (median 3.2-year follow-up). Intensive SBP treatment could prevent 84,300 (95% CI 80,800-87,920) CVD events per year in 14.1 million SPRINT-eligible US adults; 29,400 and 28,600 would be in 7.0 million individuals with medium or high predicted benefit, respectively. CONCLUSIONS: Most of the population health benefit from intensive SBP goals could be achieved by treating those characterized by a previously published algorithm as having medium or high predicted benefit.

The association between antihypertensive treatment and serious adverse events by age and frailty: A cohort study.

BACKGROUND: Antihypertensives are effective at reducing the risk of cardiovascular disease, but limited data exist quantifying their association with serious adverse events, particularly in older people with frailty. This study aimed to examine this association using nationally representative electronic health record data. METHODS AND FINDINGS: This was a retrospective cohort study utilising linked data from 1,256 general practices across England held within the Clinical Practice Research Datalink between 1998 and 2018. Included patients were aged 40+ years, with a systolic blood pressure reading between 130 and 179 mm Hg, and not previously prescribed antihypertensive treatment. The main exposure was defined as a first prescription of antihypertensive treatment. The primary outcome was hospitalisation or death within 10 years from falls. Secondary outcomes were hypotension, syncope, fractures, acute kidney injury, electrolyte abnormalities, and primary care attendance with gout. The association between treatment and these serious adverse events was examined by Cox regression adjusted for propensity score. This propensity score was generated from a multivariable logistic regression model with patient characteristics, medical history and medication prescriptions as covariates, and new antihypertensive treatment as the outcome. Subgroup analyses were undertaken by age and frailty. Of 3,834,056 patients followed for a median of 7.1 years, 484,187 (12.6%) were prescribed new antihypertensive treatment in the 12 months before the index date (baseline). Antihypertensives were associated with an increased risk of hospitalisation or death from falls (adjusted hazard ratio [aHR] 1.23, 95% confidence interval (CI) 1.21 to 1.26), hypotension (aHR 1.32, 95% CI 1.29 to 1.35), syncope (aHR 1.20, 95% CI 1.17 to 1.22), acute kidney injury (aHR 1.44, 95% CI 1.41 to 1.47), electrolyte abnormalities (aHR 1.45, 95% CI 1.43 to 1.48), and primary care attendance with gout (aHR 1.35, 95% CI 1.32 to 1.37). The absolute risk of serious adverse events with treatment was very low, with 6 fall events per 10,000 patients treated per year. In older patients (80 to 89 years) and those with severe frailty, this absolute risk was increased, with 61 and 84 fall events per 10,000 patients treated per year (respectively). Findings were consistent in sensitivity analyses using different approaches to address confounding and taking into account the competing risk of death. A strength of this analysis is that it provides evidence regarding the association between antihypertensive treatment and serious adverse events, in a population of patients more representative than those enrolled in previous randomised controlled trials. Although treatment effect estimates fell within the 95% CIs of those from such trials, these analyses were observational in nature and so bias from unmeasured confounding cannot be ruled out. CONCLUSIONS: Antihypertensive treatment was associated with serious adverse events. Overall, the absolute risk of this harm was low, with the exception of older patients and those with moderate to severe frailty, where the risks were similar to the likelihood of benefit from treatment. In these populations, physicians may want to consider alternative approaches to management of blood pressure and refrain from prescribing new treatment.

AddREssing Social Determinants TO pRevent hypErtension (The RESTORE Network): Overview of the Health Equity Research Network to Prevent Hypertension.

BACKGROUND: The American Heart Association funded a Health Equity Research Network on the prevention of hypertension, the RESTORE Network, as part of its commitment to achieving health equity in all communities. This article provides an overview of the RESTORE Network. METHODS: The RESTORE Network includes five independent, randomized trials testing approaches to implement non-pharmacological interventions that have been proven to lower blood pressure (BP). The trials are community-based, taking place in churches in rural Alabama, mobile health units in Michigan, barbershops in New York, community health centers in Maryland, and food deserts in Massachusetts. Each trial employs a hybrid effectiveness-implementation research design to test scalable and sustainable strategies that mitigate social determinants of health (SDOH) that contribute to hypertension in Black communities. The primary outcome in each trial is change in systolic BP. The RESTORE Network Coordinating Center has five cores: BP measurement, statistics, intervention, community engagement, and training that support the trials. Standardized protocols, data elements and analysis plans were adopted in each trial to facilitate cross-trial comparisons of the implementation strategies, and application of a standard costing instrument for health economic evaluations, scale up, and policy analysis. Herein, we discuss future RESTORE Network research plans and policy outreach activities designed to advance health equity by preventing hypertension. CONCLUSIONS: The RESTORE Network was designed to promote health equity in the US by testing effective and sustainable implementation strategies focused on addressing SDOH to prevent hypertension among Black adults.

Effectiveness and Cost-Effectiveness of Team-Based Care for Hypertension: A Meta-Analysis and Simulation Study.

BACKGROUND: Team-based care (TBC), a team of ≥2 healthcare professionals working collaboratively toward a shared clinical goal, is a recommended strategy to manage blood pressure (BP). However, the most effective and cost-effective TBC strategy is unknown. METHODS: A meta-analysis of clinical trials in US adults (aged ≥20 years) with uncontrolled hypertension (≥140/90 mm Hg) was performed to estimate the systolic BP reduction for TBC strategies versus usual care at 12 months. TBC strategies were stratified by the inclusion of a nonphysician team member who could titrate antihypertensive medications. The validated BP Control Model-Cardiovascular Disease Policy Model was used to project the expected BP reductions out to 10 years and simulate cardiovascular disease events, direct healthcare costs, quality-adjusted life years, and cost-effectiveness of TBC with physician and nonphysician titration. RESULTS: Among 19 studies comprising 5993 participants, the 12-month systolic BP change versus usual care was -5.0 (95% CI, -7.9 to -2.2) mm Hg for TBC with physician titration and -10.5 (-16.2 to -4.8) mm Hg for TBC with nonphysician titration. Relative to usual care at 10 years, TBC with nonphysician titration was estimated to cost $95 (95% uncertainty interval, -$563 to $664) more per patient and gain 0.022 (0.003-0.042) quality-adjusted life years, costing $4400/quality-adjusted life year gained. TBC with physician titration was estimated to cost more and gain fewer quality-adjusted life years than TBC with nonphysician titration. CONCLUSIONS: TBC with nonphysician titration yields superior hypertension outcomes compared with other strategies and is a cost-effective way to reduce hypertension-related morbidity and mortality in the United States.

Cost-effectiveness of Sodium-Glucose Cotransporter-2 Inhibitors for the Treatment of Heart Failure With Preserved Ejection Fraction.

Importance: Adding a sodium-glucose cotransporter-2 inhibitor (SGLT2-I) to standard-of-care treatment in patients with heart failure with preserved ejection fraction (HFpEF) reduces the risk of a composite outcome of worsening heart failure or cardiovascular mortality, but the cost-effectiveness in US patients with HFpEF is uncertain. Objective: To evaluate the lifetime cost-effectiveness of standard therapy plus an SGLT2-I compared with standard therapy in individuals with HFpEF. Design, Setting, and Participants: In this economic evaluation conducted from September 8, 2021, to December 12, 2022, a state-transition Markov model simulated monthly health outcomes and direct medical costs. Input parameters including hospitalization rates, mortality rates, costs, and utilities were extracted from HFpEF trials, published literature, and publicly available data sets. The base-case annual cost of SGLT2-I was $4506. A simulated cohort with similar characteristics as participants of the Empagliflozin in Heart Failure With a Preserved Ejection Fraction (EMPEROR-Preserved) and Dapagliflozin in Heart Failure With Mildly Reduced or Preserved Ejection Fraction (DELIVER) trials was used. Exposures: Standard of care plus SGLT2-I vs standard of care. Main Outcomes and Measures: The model simulated hospitalizations, urgent care visits, and cardiovascular and noncardiovascular death. Future medical costs and benefits were discounted by 3% per year. Main outcomes were quality-adjusted life-years (QALYs), direct medical costs (2022 US dollars), and incremental cost-effectiveness ratio (ICER) of SGLT2-I therapy from a US health care sector perspective. The ICER of SGLT2-I therapy was evaluated according to the American College of Cardiology/American Heart Association value framework (high value: <$50 000; intermediate value: $50 000 to <$150 000; and low value: ≥$150 000). Results: The simulated cohort had a mean (SD) age of 71.7 (9.5) years and 6828 of 12 251 participants (55.7%) were male. Standard of care plus SGLT2-I increased quality-adjusted survival by 0.19 QALYs at an increased cost of $26 300 compared with standard of care. The resulting ICER was $141 200 per QALY gained, with 59.1% of 1000 probabilistic iterations indicating intermediate value and 40.9% indicating low value. The ICER was most sensitive to SGLT2-I costs and effect of SGLT2-I therapy on cardiovascular death (eg, increasing to $373 400 per QALY gained if SGLT2-I therapy was assumed to have no effect on mortality). Conclusions and Relevance: Results of this economic evaluation suggest that at 2022 drug prices, adding an SGLT2-I to standard of care was of intermediate or low economic value compared with standard of care in US adults with HFpEF. Efforts to expand access to SGLT2-I for individuals with HFpEF should be coupled with efforts to lower the cost of SGLT2-I therapy.

Cost-effectiveness analysis of initial treatment with single-pill combination antihypertensive medications.

Hypertension guidelines recommend initiating treatment with single pill combination (SPC) antihypertensive medications, but SPCs are used by only one-third of treated hypertensive US adults. This analysis estimated the cost-effectiveness of initial treatment with SPC dual antihypertensive medications compared with usual care monotherapy in hypertensive US adults.The validated BP Control Model-Cardiovascular Disease (CVD) Policy Model simulated initial SPC dual therapy (two half-standard doses in a single pill) compared with initial usual care monotherapy (half-standard dose when baseline systolic BP < 20 mmHg above goal and one standard dose when ≥20 mmHg above goal). Secondary analyses examined equivalent dose monotherapy (one standard dose) and equivalent dose dual therapy as separate pills (two half-standard doses). The primary outcomes were direct healthcare costs, quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratio (ICER) over 10 years from a US healthcare sector perspective.At 10 years, initial dual drug SPC was projected to yield 0.028 (95%UI 0.008 to 0.051) more QALYs at no greater cost ($73, 95%UI -$1 983 to $1 629) than usual care monotherapy. In secondary analysis, SPC dual therapy was cost-effective vs. equivalent dose monotherapy (ICER $8 000/QALY gained) and equivalent dose dual therapy as separate pills (ICER $57 000/QALY gained). At average drug prices, initiating antihypertensive treatment with SPC dual therapy is more effective at no greater cost than usual care initial monotherapy and has the potential to improve BP control rates and reduce the burden of CVD in the US.

The Health and Economic Impact of Using a Sugar Sweetened Beverage Tax to Fund Fruit and Vegetable Subsidies in New York City: A Modeling Study.

Low fruit and vegetable (FV) intake and high sugar-sweetened beverage (SSB) consumption are independently associated with an increased risk of developing cardiovascular disease (CVD). Many people in New York City (NYC) have low FV intake and high SSB consumption, partly due to high cost of fresh FVs and low cost of and easy access to SSBs. A potential implementation of an SSB tax and an FV subsidy program could result in substantial public health and economic benefits. We used a validated microsimulation model for predicting CVD events to estimate the health impact and cost-effectiveness of SSB taxes, FV subsidies, and funding FV subsidies with an SSB tax in NYC. Population demographics and health profiles were estimated using data from the NYC Health and Nutrition Examination Survey. Policy effects and price elasticity were derived from recent meta-analyses. We found that funding FV subsidies with an SSB tax was projected to be the most cost-effective policy from the healthcare sector perspective. From the societal perspective, the most cost-effective policy was SSB taxes. All policy scenarios could prevent more CVD events and save more healthcare costs among men compared to women, and among Black vs. White adults. Public health practitioners and policymakers may want to consider adopting this combination of policy actions, while weighing feasibility considerations and other unintended consequences.

Projected Impact of Nonpharmacologic Management of Stage 1 Hypertension Among Lower-Risk US Adults.

Background: The 2017 American College of Cardiology (ACC)/American Heart Association (AHA) guidelines newly classified 31 million US adults as having stage 1 hypertension. The ACC/AHA guidelines recommend behavioral change without pharmacology for the low-risk portion of this group. However, the nationwide reduction in cardiovascular disease (CVD) and associated healthcare expenditures achievable by evidence-based dietary improvements, sustained weight loss, adequate physical activity, and alcohol moderation remain unquantified. We estimated the effect of systolic BP (SBP) control and behavioral changes on 10-year CVD outcomes and costs. Methods: We used the CVD Policy Model to simulate CVD events, mortality, and healthcare costs among US adults aged 35-64. We simulated interventions on a target population, identified from the 2015-2018 National Health and Nutrition Examination Survey, with low-risk stage 1 systolic hypertension: defined as untreated SBP 130-139 mmHg and diastolic BP <90 mmHg; no history of CVD, diabetes, or chronic kidney disease; and low 10-year risk of CVD. We used published meta-analyses and trials to estimate the effects of behavior modification on SBP. We assessed the extent to which intermittent healthcare utilization or partial uptake of nonpharmacologic therapy would decrease CVD events prevented. Results: Controlling SBP to <130 mmHg among the estimated 8.8 million U.S. adults (51% women) in the target population could prevent 26,100 CVD events, avoid 2,900 deaths, and save $1.6 billion in healthcare costs over 10 years. The Dietary Approaches to Stop Hypertension (DASH) diet could prevent 16,000 CVD events among men and 12,000 among women over a decade. Other nonpharmacologic interventions could avert between 3,700 and 19,500 CVD events. However, only 5.5 million (61%) of the target population regularly utilized healthcare where recommended clinician counseling could occur. Conclusions: As only two-thirds of U.S. adults with Stage 1 hypertension regularly receive medical care, substantial benefits to cardiovascular health and associated costs may only stem from policies that promote widespread adoption and sustained adherence of nonpharmacologic therapy. Future work should quantify the population-level costs, benefits, and efficacy of improving the food system and local infrastructure on health behavior change.

Intensive Versus Standard Blood Pressure Lowering and Days Free of Cardiovascular Events and Serious Adverse Events: a Post Hoc Analysis of Systolic Blood Pressure Intervention Trial.

BACKGROUND: Communication of the benefits and harms of blood pressure lowering strategy is crucial for shared decision-making. OBJECTIVES: To quantify the effect of intensive versus standard systolic blood pressure lowering in terms of the number of event-free days DESIGN: Post hoc analysis of the Systolic Blood Pressure Intervention Trial PARTICIPANTS: A total of 9361 adults 50 years or older without diabetes or stroke who had a systolic blood pressure of 130-180 mmHg and elevated cardiovascular risk INTERVENTIONS: Intensive (systolic blood pressure goal <120 mmHg) versus standard blood pressure lowering (<140 mmHg) MAIN MEASURES: Days free of major adverse cardiovascular events (MACE), serious adverse events (SAE), and monitored adverse events (hypotension, syncope, bradycardia, electrolyte abnormalities, injurious falls, or acute kidney injury) over a median follow-up of 3.33 years KEY RESULTS: The intensive treatment group gained 14.7 more MACE-free days over 4 years (difference, 14.7 [95% confidence interval: 5.1, 24.4] days) than the standard treatment group. The benefit of the intensive treatment varied by cognitive function (normal: difference, 40.7 [13.0, 68.4] days; moderate-to-severe impairment: difference, -15.0 [-56.5, 26.4] days; p-for-interaction=0.009) and self-rated health (excellent: difference, -22.7 [-51.5, 6.1] days; poor: difference, 156.1 [31.1, 281.2] days; p-for-interaction=0.001). The mean overall SAE-free days were not significantly different between the treatments (difference, -14.8 [-35.3, 5.7] days). However, the intensive treatment group had 28.5 fewer monitored adverse event-free days than the standard treatment group (difference, -28.5 [-40.3, -16.7] days), with significant variations by frailty status (non-frail: difference, 38.8 [8.4, 69.2] days; frail: difference, -15.5 [-46.6, 15.7] days) and self-rated health (excellent: difference, -12.9 [-45.5, 19.7] days; poor: difference, 180.6 [72.9, 288.4] days; p-for-interaction <0.001). CONCLUSIONS: Over 4 years, intensive systolic blood pressure lowering provides, on average, 14.7 more MACE-free days than standard treatment, without any difference in SAE-free days. Whether this time-based effect summary improves shared decision-making remains to be elucidated. TRIAL REGISTRATION: ClinicalTrials.gov Registration: NCT01206062.

An efficient approach for optimizing the cost-effective individualized treatment rule using conditional random forest.

Evidence from observational studies has become increasingly important for supporting healthcare policy making via cost-effectiveness analyses. Similar as in comparative effectiveness studies, health economic evaluations that consider subject-level heterogeneity produce individualized treatment rules that are often more cost-effective than one-size-fits-all treatment. Thus, it is of great interest to develop statistical tools for learning such a cost-effective individualized treatment rule under the causal inference framework that allows proper handling of potential confounding and can be applied to both trials and observational studies. In this paper, we use the concept of net-monetary-benefit to assess the trade-off between health benefits and related costs. We estimate cost-effective individualized treatment rule as a function of patients' characteristics that, when implemented, optimizes the allocation of limited healthcare resources by maximizing health gains while minimizing treatment-related costs. We employ the conditional random forest approach and identify the optimal cost-effective individualized treatment rule using net-monetary-benefit-based classification algorithms, where two partitioned estimators are proposed for the subject-specific weights to effectively incorporate information from censored individuals. We conduct simulation studies to evaluate the performance of our proposals. We apply our top-performing algorithm to the NIH-funded Systolic Blood Pressure Intervention Trial to illustrate the cost-effectiveness gains of assigning customized intensive blood pressure therapy.