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.

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.

Patterns, Prognostic Implications, and Rural-Urban Disparities in Optimal GDMT Following HFrEF Diagnosis Among Medicare Beneficiaries.

BACKGROUND: Patterns and disparities in guideline-directed medical therapy (GDMT) uptake for heart failure with reduced ejection fraction (HFrEF) across rural vs urban regions are not well described. OBJECTIVES: This study aims to evaluate patterns, prognostic implications, and rural-urban differences in GDMT use among Medicare beneficiaries following new-onset HFrEF. METHODS: Patients with a diagnosis of new-onset HFrEF in a 5% Medicare sample with available data for Part D medication use were identified from January 2015 through December 2020. The primary exposure was residence in rural vs urban zip codes. Optimal triple GDMT was defined as ≥50% of the target daily dose of beta-blockers, ≥50% of the target daily dose of angiotensin-converting enzyme inhibitors/angiotensin receptor blocker or any dose of sacubitril/valsartan, and any dose of mineralocorticoid receptor antagonist. The association between the achievement of optimal GDMT over time following new-onset HFrEF diagnosis and risk of all-cause mortality and subsequent HF hospitalization was also evaluated using adjusted Cox models. The association between living in rural vs urban location and time to optimal GDMT achievement over a 12-month follow-up was assessed using cumulative incidence curves and adjusted Fine-Gray subdistribution hazard models. RESULTS: A total of 41,296 patients (age: 76.7 years; 15.0% Black; 27.6% rural) were included. Optimal GDMT use over the 12-month follow-up was low, with 22.5% initiated on any dose of triple GDMT and 9.1% on optimal GDMT doses. Optimal GDMT on follow-up was significantly associated with a lower risk of death (HR: 0.89 [95% CI: 0.85-0.94]; P < 0.001) and subsequent HF hospitalization (HR: 0.93 [95% CI: 0.87-0.98]; P = 0.02). Optimal GDMT use at 12 months was significantly lower among patients living in rural (vs urban) areas (8.4% vs 9.3%; P = 0.02). In adjusted analysis, living in rural (vs urban) locations was associated with a significantly lower probability of achieving optimal GDMT (HR: 0.92 [95% CI: 0.86-0.98]; P = 0.01 Differences in optimal GDMT use following HFrEF diagnosis accounted for 16% of excess mortality risk among patients living in rural (vs urban) areas. CONCLUSIONS: Use of optimal GDMT following new-onset HFrEF diagnosis is low, with substantially lower use noted among patients living in rural vs urban locations. Suboptimal GDMT use following new-onset HFrEF was associated with an increased risk of mortality and subsequent HF hospitalization.

Identifying Patients for Intensive Blood Pressure Treatment Based on Cognitive Benefit: A Secondary Analysis of the SPRINT Randomized Clinical Trial.

Importance: Intensive vs standard treatment to lower systolic blood pressure (SBP) reduces risk of mild cognitive impairment (MCI) or dementia; however, the magnitude of cognitive benefit likely varies among patients. Objective: To estimate the magnitude of cognitive benefit of intensive vs standard systolic BP (SBP) treatment. Design, Setting, and Participants: In this ad hoc secondary analysis of the Systolic Blood Pressure Intervention Trial (SPRINT), 9361 randomized clinical trial participants 50 years or older with high cardiovascular risk but without a history of diabetes, stroke, or dementia were followed up. The SPRINT trial was conducted between November 1, 2010, and August 31, 2016, and the present analysis was completed on October 31, 2022. Intervention: Systolic blood pressure treatment to an intensive (<120 mm Hg) vs standard (<140 mm Hg) target. Main Outcomes and Measures: The primary outcome was a composite of adjudicated probable dementia or amnestic MCI. Results: A total of 7918 SPRINT participants were included in the analysis; 3989 were in the intensive treatment group (mean [SD] age, 67.9 [9.2] years; 2570 [64.4%] men; 1212 [30.4%] non-Hispanic Black) and 3929 were in the standard treatment group (mean [SD] age, 67.9 [9.4] years; 2570 [65.4%] men; 1249 [31.8%] non-Hispanic Black). Over a median follow-up of 4.13 (IQR, 3.50-5.88) years, there were 765 and 828 primary outcome events in the intensive treatment group and standard treatment group, respectively. Older age (hazard ratio [HR] per 1 SD, 1.87 [95% CI, 1.78-1.96]), Medicare enrollment (HR per 1 SD, 1.42 [95% CI, 1.35-1.49]), and higher baseline serum creatinine level (HR per 1 SD, 1.24 [95% CI, 1.19-1.29]) were associated with higher risk of the primary outcome, while better baseline cognitive functioning (HR per 1 SD, 0.43 [95% CI, 0.41-0.44]) and active employment status (HR per 1 SD, 0.44 [95% CI, 0.42-0.46]) were associated with lower risk of the primary outcome. Risk of the primary outcome by treatment goal was estimated accurately based on similar projected and observed absolute risk differences (C statistic = 0.79). Higher baseline risk for the primary outcome was associated with greater benefit (ie, larger absolute reduction of probable dementia or amnestic MCI) of intensive vs standard treatment across the full range of estimated baseline risk. Conclusions and Relevance: In this secondary analysis of the SPRINT trial, participants with higher baseline projected risk of probable dementia or amnestic MCI gained greater absolute cognitive benefit from intensive vs standard SBP treatment in a monotonic fashion. Trial Registration: ClinicalTrials.gov Identifier: NCT01206062.

Association of New Use of Antihypertensives That Stimulate vs Inhibit Type 2 and 4 Angiotensin II Receptors With Dementia Among Medicare Beneficiaries.

Importance: Prevalent use of antihypertensive medications that stimulate type 2 and 4 angiotensin II receptors, compared with those that do not stimulate these receptors, has been associated with a lower risk of dementia. However, previous studies were limited by inclusion of individuals with prevalent hypertension and a history of antihypertensive use prior to the start of the study, which can introduce bias. Objective: To examine the association of new use of antihypertensive medication regimens that stimulate vs inhibit type 2 and 4 angiotensin II receptors with Alzheimer disease and related dementias (ADRD) among Medicare beneficiaries. Design, Setting, and Participants: This cohort study was conducted among 57 773 Medicare fee-for-service beneficiaries (January 1, 2006, through December 31, 2018) aged 65 years or older with incident hypertension. Data analysis was conducted from January 1 through June 30, 2022. Exposures: Initiation of antihypertensive medication regimens that stimulate or inhibit type 2 and 4 angiotensin II receptors, or mixed regimens (both stimulating and inhibiting), with the time-dependent measure being each 30-day interval. Main Outcomes and Measures: The primary outcome was time to first occurrence of ADRD (Centers for Medicare & Medicaid Services Chronic Conditions Data Warehouse definition). Cox proportional hazards regression modeling with time-dependent variables was performed to estimate the association between time-dependent treatment groups and time to ADRD, after adjusting for sociodemographic and clinical characteristics. Results: The sample included 57 773 Medicare beneficiaries (36 348 women [62.9%]; mean [SD] age, 73.8 [6.3] years; 2954 [5.1%] Black, 1545 [2.7%] Hispanic; 50 184 [86.9%] White, and 3090 [5.4%] Other individuals [the Other category included individuals of American Indian, Asian, other, or unknown race and ethnicity]). During a median of 6.9 years (IQR, 4.7-9.3 years) of follow-up, the unadjusted incidence density rate of ADRD was 2.2 cases per 100 person-years (95% CI, 2.1-2.4 cases per 100 person-years) for the group receiving regimens that stimulate type 2 and 4 angiotensin II receptors compared with 3.1 cases per 100 person-years (95% CI, 3.0-3.2 cases per 100 person-years) for the group receiving regimens that inhibit type 2 and 4 angiotensin II receptors and 2.7 cases per 100 person-years (95% CI, 2.6-2.9 cases per 100 person-years) for the group receiving mixed treatment regimens. In adjusted Cox proportional hazards regression modeling, stimulating treatment was associated with a statistically significant 16% reduction in the hazard of ADRD compared with inhibiting treatment (hazard ratio, 0.84; 95% CI, 0.79-0.90). Mixed regimen use was also associated with reduced hazards of ADRD compared with the inhibiting group (hazard ratio, 0.90; 95% CI, 0.84-0.96). Conclusions and Relevance: This cohort study of Medicare beneficiaries suggests that use of antihypertensive medications that stimulate type 2 and 4 angiotensin II receptors was associated with lower risk of ADRD compared with antihypertensive medications that inhibit these receptors. Confirmation is needed in a randomized trial.

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.

Cost-Effectiveness of Masked Hypertension Screening and Treatment in US Adults With Suspected Masked Hypertension: A Simulation Study.

BACKGROUND: Recent US blood pressure (BP) guidelines recommend using ambulatory BP monitoring (ABPM) or home BP monitoring (HBPM) to screen adults for masked hypertension. However, limited evidence exists of the expected long-term effects of screening for and treating masked hypertension. METHODS: We estimated the lifetime health and economic outcomes of screening for and treating masked hypertension using the Cardiovascular Disease (CVD) Policy Model, a validated microsimulation model. We simulated a cohort of 100,000 US adults aged ≥20 years with suspected masked hypertension (i.e., office BP 120-129/<80 mm Hg, not taking antihypertensive medications, without CVD history). We compared usual care only (i.e., no screening), usual care plus ABPM, and usual care plus HBPM. We projected total direct healthcare costs (2021 USD), quality-adjusted life years (QALYs), and incremental cost-effectiveness ratios. Future costs and QALYs were discounted 3% annually. Secondary outcomes included CVD events and serious adverse events. RESULTS: Relative to usual care, adding masked hypertension screening and treatment with ABPM and HBPM was projected to prevent 14.3 and 20.5 CVD events per 100,000 person-years, increase the proportion experiencing any treatment-related serious adverse events by 2.7 and 5.1 percentage points, and increase mean total costs by $1,076 and $1,046, respectively. Compared with usual care, adding ABPM was estimated to cost $85,164/QALY gained. HBPM resulted in lower QALYs than usual care due to increased treatment-related adverse events and pill-taking disutility. CONCLUSIONS: The results from our simulation study suggest screening with ABPM and treating masked hypertension is cost-effective in US adults with suspected masked hypertension.

Cost-effectiveness of Icosapent Ethyl for High-risk Patients With Hypertriglyceridemia Despite Statin Treatment.

Importance: The Reduction of Cardiovascular Events With Icosapent Ethyl-Intervention Trial (REDUCE-IT) demonstrated the efficacy of icosapent ethyl (IPE) for high-risk patients with hypertriglyceridemia and known cardiovascular disease or diabetes and at least 1 other risk factor who were treated with statins. Objective: To estimate the cost-effectiveness of IPE compared with standard care for high-risk patients with hypertriglyceridemia despite statin treatment. Design, Setting, and Participants: An in-trial cost-effectiveness analysis was performed using patient-level study data from REDUCE-IT, and a lifetime analysis was performed using a microsimulation model and data from published literature. The study included 8179 patients with hypertriglyceridemia despite stable statin therapy recruited between November 21, 2011, and May 31, 2018. Analyses were performed from a US health care sector perspective. Statistical analysis was performed from March 1, 2018, to October 31, 2021. Interventions: Patients were randomly assigned to IPE, 4 g/d, or placebo and were followed up for a median of 4.9 years (IQR, 3.5-5.3 years). The cost of IPE was $4.16 per day after rebates using SSR Health net cost (SSR cost) and $9.28 per day with wholesale acquisition cost (WAC). Main Outcomes and Measures: Main outcomes were incremental quality-adjusted life-years (QALYs), total direct health care costs (2019 US dollars), and cost-effectiveness. Results: A total of 4089 patients (2927 men [71.6%]; median age, 64.0 years [IQR, 57.0-69.0 years]) were randomly assigned to receive IPE, and 4090 patients (2895 men [70.8%]; median age, 64.0 years [IQR, 57.0-69.0 years]) were randomly assigned to receive standard care. Treatment with IPE yielded more QALYs than standard care both in trial (3.34 vs 3.27; mean difference, 0.07 [95% CI, 0.01-0.12]) and over a lifetime projection (10.59 vs 10.35; mean difference, 0.24 [95% CI, 0.15-0.33]). In-trial, total health care costs were higher with IPE using either SSR cost ($18 786) or WAC ($24 544) than with standard care ($17 273; mean difference from SSR cost, $1513 [95% CI, $155-$2870]; mean difference from WAC, $7271 [95% CI, $5911-$8630]). Icosapent ethyl cost $22 311 per QALY gained using SSR cost and $107 218 per QALY gained using WAC. Over a lifetime, IPE was projected to be cost saving when using SSR cost ($195 276) compared with standard care ($197 064; mean difference, -$1788 [95% CI, -$9735 to $6159]) but to have higher costs when using WAC ($202 830) compared with standard care (mean difference, $5766 [95% CI, $1094-$10 438]). Compared with standard care, IPE had a 58.4% lifetime probability of costing less and being more effective when using SSR cost and an 89.4% probability of costing less than $50 000 per QALY gained when using SSR cost and a 72.5% probability of costing less than $50 000 per QALY gained when using WAC. Conclusions and Relevance: This study suggests that, both in-trial and over the lifetime, IPE offers better cardiovascular outcomes than standard care in REDUCE-IT participants at common willingness-to-pay thresholds.

Analysis of Therapeutic Inertia and Race and Ethnicity in the Systolic Blood Pressure Intervention Trial: A Secondary Analysis of a Randomized Clinical Trial.

Importance: Therapeutic inertia may contribute to racial and ethnic differences in blood pressure (BP) control. Objective: To determine the association between race and ethnicity and therapeutic inertia in the Systolic Blood Pressure Intervention Trial (SPRINT). Design, Setting, and Participants: This cross-sectional study was a secondary analysis of data from SPRINT, a randomized clinical trial comparing intensive (<120 mm Hg) vs standard (<140 mm Hg) systolic BP treatment goals. Participants were enrolled between November 8, 2010, and March 15, 2013, with a median follow-up 3.26 years. Participants included adults aged 50 years or older at high risk for cardiovascular disease but without diabetes, previous stroke, or heart failure. The present analysis was restricted to participant visits with measured BP above the target goal. Analyses for the present study were performed in from October 2020 through March 2021. Exposures: Self-reported race and ethnicity, mutually exclusively categorized into groups of Hispanic, non-Hispanic Black, or non-Hispanic White participants. Main Outcomes and Measures: Therapeutic inertia, defined as no antihypertensive medication intensification at each study visit where the BP was above target goal. The association between self-reported race and ethnicity and therapeutic inertia was estimated using generalized estimating equations and stratified by treatment group. Antihypertensive medication use was assessed with pill bottle inventories at each visit. Blood pressure was measured using an automated device. Results: A total of 8556 participants, including 4141 in the standard group (22 844 participant-visits; median age, 67.0 years [IQR, 61.0-76.0 years]; 1467 women [35.4%]) and 4415 in the intensive group (35 453 participant-visits; median age, 67.0 years [IQR, 61.0-76.0 years]; 1584 women [35.9%]) with at least 1 eligible study visit were included in the present analysis. Among non-Hispanic White, non-Hispanic Black, and Hispanic participants, the overall prevalence of therapeutic inertia in the standard vs intensive groups was 59.8% (95% CI, 58.9%-60.7%) vs 56.0% (95% CI, 55.2%-56.7%), 56.8% (95% CI, 54.4%-59.2%) vs 54.5% (95% CI, 52.4%-56.6%), and 59.7% (95% CI, 56.5%-63.0%) vs 51.0% (95% CI, 47.4%-54.5%), respectively. The adjusted odds ratios in the standard and intensive groups for therapeutic inertia associated with non-Hispanic Black vs non-Hispanic White participants were 0.85 (95% CI, 0.79-0.92) and 0.94 (95% CI, 0.88-1.01), respectively. The adjusted odds ratios for therapeutic inertia comparing Hispanic vs non-Hispanic White participants were 1.00 (95% CI, 0.90-1.13) and 0.89 (95% CI, 0.79-1.00) in the standard and intensive groups, respectively. Conclusions and Relevance: Among SPRINT participants above BP target goal, this cross-sectional study found that therapeutic inertia prevalence was similar or lower for non-Hispanic Black and Hispanic participants compared with non-Hispanic White participants. These findings suggest that a standardized approach to BP management, as used in SPRINT, may help ensure equitable care and could reduce the contribution of therapeutic inertia to disparities in hypertension. Trial Registration: ClinicalTrials.gov identifier: NCT01206062.

Estimating the optimal individualized treatment rule from a cost-effectiveness perspective.

Optimal individualized treatment rules (ITRs) provide customized treatment recommendations based on subject characteristics to maximize clinical benefit in accordance with the objectives in precision medicine. As a result, there is growing interest in developing statistical tools for estimating optimal ITRs in evidence-based research. In health economic perspectives, policy makers consider the tradeoff between health gains and incremental costs of interventions to set priorities and allocate resources. However, most work on ITRs has focused on maximizing the effectiveness of treatment without considering costs. In this paper, we jointly consider the impact of effectiveness and cost on treatment decisions and define ITRs under a composite-outcome setting, so that we identify the most cost-effective ITR that accounts for individual-level heterogeneity through direct optimization. In particular, we propose a decision-tree-based statistical learning algorithm that uses a net-monetary-benefit-based reward to provide nonparametric estimations of the optimal ITR. We provide several approaches to estimating the reward underlying the ITR as a function of subject characteristics. We present the strengths and weaknesses of each approach and provide practical guidelines by comparing their performance in simulation studies. We illustrate the top-performing approach from our simulations by evaluating the projected 15-year personalized cost-effectiveness of the intensive blood pressure control of the Systolic Blood Pressure Intervention Trial (SPRINT) study.

Multiple Social Vulnerabilities to Health Disparities and Hypertension and Death in the REGARDS Study.

Social vulnerabilities increase the risk of developing hypertension and lower life expectancy, but the effect of an individual's overall vulnerability burden is unknown. Our objective was to determine the association of social vulnerability count and the risk of developing hypertension or dying over 10 years and whether these associations vary by race. We used the REGARDS study (Reasons for Geographic and Racial Differences in Stroke) and included participants without baseline hypertension. The primary exposure was the count of social vulnerabilities defined across economic, education, health and health care, neighborhood and built environment, and social and community context domains. Among 5425 participants of mean age 64±10 SD years of which 24% were Black participants, 1468 (31%) had 1 vulnerability and 717 (15%) had ≥2 vulnerabilities. Compared with participants without vulnerabilities, the adjusted relative risk ratio for developing hypertension was 1.16 (95% CI, 0.99-1.36) and 1.49 (95% CI, 1.20-1.85) for individuals with 1 and ≥2 vulnerabilities, respectively. The adjusted relative risk ratio for death was 1.55 (95% CI, 1.24-1.93) and 2.30 (95% CI, 1.75-3.04) for individuals with 1 and ≥2 vulnerabilities, respectively. A greater proportion of Black participants developed hypertension and died than did White participants (hypertension, 38% versus 31%; death, 25% versus 20%). The vulnerability count association was strongest in White participants (P value for vulnerability count×race interaction: hypertension=0.046, death=0.015). Overall, a greater number of socially determined vulnerabilities was associated with progressively higher risk of developing hypertension, and an even higher risk of dying over 10 years.

Inequities in Hypertension Control in the United States Exposed and Exacerbated by COVID-19 and the Role of Home Blood Pressure and Virtual Health Care During and After the COVID-19 Pandemic.

The COVID-19 pandemic is a public health crisis, having killed more than 514 000 US adults as of March 2, 2021. COVID-19 mitigation strategies have unintended consequences on managing chronic conditions such as hypertension, a leading cause of cardiovascular disease and health disparities in the United States. During the first wave of the pandemic in the United States, the combination of observed racial/ethnic inequities in COVID-19 deaths and social unrest reinvigorated a national conversation about systemic racism in health care and society. The 4th Annual University of Utah Translational Hypertension Symposium gathered frontline clinicians, researchers, and leaders from diverse backgrounds to discuss the intersection of these 2 critical social and public health phenomena and to highlight preexisting disparities in hypertension treatment and control exacerbated by COVID-19. The discussion underscored environmental and socioeconomic factors that are deeply embedded in US health care and research that impact inequities in hypertension. Structural racism plays a central role at both the health system and individual levels. At the same time, virtual healthcare platforms are being accelerated into widespread use by COVID-19, which may widen the divide in healthcare access across levels of wealth, geography, and education. Blood pressure control rates are declining, especially among communities of color and those without health insurance or access to health care. Hypertension awareness, therapeutic lifestyle changes, and evidence-based pharmacotherapy are essential. There is a need to improve the implementation of community-based interventions and blood pressure self-monitoring, which can help build patient trust and increase healthcare engagement.

Cost-Effectiveness and Challenges of Implementing Intensive Blood Pressure Goals and Team-Based Care.

PURPOSE OF REVIEW: Review the effectiveness, cost-effectiveness, and implementation challenges of intensive blood pressure (BP) control and team-based care initiatives. RECENT FINDINGS: Intensive BP control is an effective and cost-effective intervention; yet, implementation in routine clinical practice is challenging. Several models of team-based care for hypertension management have been shown to be more effective than usual care to control BP. Additional research is needed to determine the cost-effectiveness of team-based care models relative to one another and as they relate to implementing intensive BP goals. As a focus of healthcare shifts to value (i.e., cost, effectiveness, and patient preferences), formal cost-effectiveness analyses will inform which team-based initiatives hold the highest value in different healthcare settings with different populations and needs. Several challenges, including clinical inertia, financial investment, and billing restrictions for pharmacist-delivered services, will need to be addressed in order to improve public health through intensive BP control and team-based care.

The economic burden of hypertriglyceridemia among US adults with diabetes or atherosclerotic cardiovascular disease on statin therapy.

BACKGROUND: Hypertriglyceridemia (HTG) is associated with increased cardiovascular disease (CVD) risk. However, the cost burden of HTG-related CVD in high-risk US adults on statins has not been well characterized. OBJECTIVE: We estimated the HTG-related health care cost burden among US adults with CVD or diabetes taking statin therapy. METHODS: We estimated population sizes and annual health care costs among US adults aged ≥45 years with diabetes or CVD taking statin therapy with normal triglycerides (TGs) defined as TG < 150 mg/dL compared with those with HTG defined as TG ≥ 150 mg/dL. Population sizes were estimated from the 2007-2014 National Health and Nutrition Examination Surveys. Adjusted mean total annual health care costs in 2015 US dollars were estimated using the Optum Research Database. The annual total health care cost burden was estimated by multiplying the population size by the mean annual total incremental health care costs overall and within subgroups. RESULTS: There were 6.2 (95% confidence interval [CI], 5.4 - 7.1) million and 12.0 (95% CI, 11.1 - 12.9) million US adults aged ≥45 years with diabetes and/or CVD on statin therapy with TG ≥ 150 mg/dL and TG < 150 mg/dL, respectively. The mean adjusted incremental total one-year health care costs in adults with TG ≥ 150 mg/dL compared with those with TG < 150 mg/dL was $1730 (95% CI, $1160 - $2320). This leads to a projected annual incremental cost burden associated with HTG in patients with diabetes or CVD on statins of $10.7 billion (95% CI, $6.8 B - $14.6 B). CONCLUSION: In US adults on statins and at high risk for CVD, the health care costs associated with HTG are substantial.

Clinical and Economic Outcomes of Ranolazine Versus Conventional Antianginals Users Among Veterans With Chronic Stable Angina Pectoris.

Real-world outcomes in patients with chronic stable angina treated with ranolazine and other antianginal medications as second- or third-line therapy are limited. In a historical cohort study of veterans with chronic stable angina, we compared time with coronary revascularization procedures, hospitalizations, and 1-year healthcare costs between new-users of ranolazine versus conventional antianginals (i.e., calcium channel blockers, ß blockers, or long-acting nitrates) as second- or third-line. Weighted regression models calculated adjusted hazard ratios (HR) at up to 8-year follow-up, and adjusted incremental costs in the first year. Weighted groups comprised 4,699 ranolazine users and 31,815 conventional antianginal users. Percutaneous coronary intervention (PCI) occurred more often in ranolazine users compared with conventional antianginal users (HR 1.16; 95% confidence intervals [CI] 1.08 to 1.25, p <0.001), and coronary artery bypass grafting occurred less often (HR 0.82; 95% CI 0.68 to 1.00, p <0.046). All-cause and atrial fibrillation (AF) hospitalizations were less common with ranolazine users compared with conventional users (all-cause: HR 0.94; 95% CI 0.90 to 0.99, p <0.010; AF:HR 0.74; 95% CI 0.67 to 0.82, p <0.001), and acute coronary syndrome was more common (HR 1.13; 95% CI 1.00 to 1.27, p <0.042). Adjusted 1-year costs were $24,517 in ranolazine users and $24,798 in conventional users (difference, $-280; 95% CI $-1,742 to $1,181, p = 0.71). In conclusion, ranolazine users had lower rates of coronary artery bypass grafting and all-cause and AF hospitalizations, but higher rates of percutaneous coronary intervention and hospitalizations due to acute coronary syndrome compared with conventional antianginal users. Healthcare costs were similar between ranolazine and conventional antianginal users.

Cost-Effectiveness of Intensive versus Standard Blood-Pressure Control.

BACKGROUND: In the Systolic Blood Pressure Intervention Trial (SPRINT), adults at high risk for cardiovascular disease who received intensive systolic blood-pressure control (target, <120 mm Hg) had significantly lower rates of death and cardiovascular disease events than did those who received standard control (target, <140 mm Hg). On the basis of these data, we wanted to determine the lifetime health benefits and health care costs associated with intensive control versus standard control. METHODS: We used a microsimulation model to apply SPRINT treatment effects and health care costs from national sources to a hypothetical cohort of SPRINT-eligible adults. The model projected lifetime costs of treatment and monitoring in patients with hypertension, cardiovascular disease events and subsequent treatment costs, treatment-related risks of serious adverse events and subsequent costs, and quality-adjusted life-years (QALYs) for intensive control versus standard control of systolic blood pressure. RESULTS: We determined that the mean number of QALYs would be 0.27 higher among patients who received intensive control than among those who received standard control and would cost approximately $47,000 more per QALY gained if there were a reduction in adherence and treatment effects after 5 years; the cost would be approximately $28,000 more per QALY gained if the treatment effects persisted for the remaining lifetime of the patient. Most simulation results indicated that intensive treatment would be cost-effective (51 to 79% below the willingness-to-pay threshold of $50,000 per QALY and 76 to 93% below the threshold of $100,000 per QALY), regardless of whether treatment effects were reduced after 5 years or persisted for the remaining lifetime. CONCLUSIONS: In this simulation study, intensive systolic blood-pressure control prevented cardiovascular disease events and prolonged life and did so at levels below common willingness-to-pay thresholds per QALY, regardless of whether benefits were reduced after 5 years or persisted for the patient's remaining lifetime. (Funded by the National Heart, Lung, and Blood Institute and others; SPRINT ClinicalTrials.gov number, NCT01206062 .).

Trends in Antihypertensive Medication Discontinuation and Low Adherence Among Medicare Beneficiaries Initiating Treatment From 2007 to 2012.

Low antihypertensive medication adherence is common. During recent years, the impact of low medication adherence on increased morbidity and healthcare costs has become more recognized, leading to interventions aimed at improving adherence. We analyzed a 5% sample of Medicare beneficiaries initiating antihypertensive medication between 2007 and 2012 to assess whether reductions occurred in discontinuation and low adherence. Discontinuation was defined as having no days of antihypertensive medication supply for the final 90 days of the 365 days after initiation. Low adherence was defined as having a proportion of days covered <80% during the 365 days after initiation among beneficiaries who did not discontinue treatment. Between 2007 and 2012, 41 135 Medicare beneficiaries in the 5% sample initiated antihypertensive medication. Discontinuation was stable during the study period (21.0% in 2007 and 21.3% in 2012; P-trend=0.451). Low adherence decreased from 37.4% in 2007 to 31.7% in 2012 (P-trend<0.001). After multivariable adjustment, the relative risk of low adherence for beneficiaries initiating treatment in 2012 versus in 2007 was 0.88 (95% confidence interval, 0.83-0.92). Low adherence was more common among racial/ethnic minorities, beneficiaries with Medicaid buy-in (an indicator of low income), and those with polypharmacy, and was less common among females, beneficiaries initiating antihypertensive medication with multiple classes or a 90-day prescription fill, with dementia, a history of stroke, and those who reached the Medicare Part D coverage gap in the previous year. In conclusion, low adherence to antihypertensive medication has decreased among Medicare beneficiaries; however, rates of discontinuation and low adherence remain high.

Cost-Effectiveness of Sacubitril-Valsartan Combination Therapy Compared With Enalapril for the Treatment of Heart Failure With Reduced Ejection Fraction.

OBJECTIVES: The objective of this study was to determine the cost-effectiveness and cost per quality-adjusted life year (QALY) gained of sacubitril-valsartan relative to enalapril for treatment of heart failure with reduced ejection fraction (HFrEF). BACKGROUND: Compared with enalapril, combination angiotensin receptor-neprilysin inhibition (ARNI), as is found in sacubitril-valsartan, reduces cardiovascular death and heart failure hospitalization rates in patients with HFrEF. METHODS: Using a Markov model, costs, effects, and cost-effectiveness were estimated for sacubitril-valsartan and enalapril therapies for the treatment of HFrEF. Patients were 60 years of age at model entry and were modeled over a lifetime (40 years) from a third-party payer perspective. Clinical probabilities were derived predominantly from PARADIGM-HF (Prospective Comparison of ARNI With ACEI to Determine Impact on Global Mortality and Morbidity in Heart Failure). All costs and effects were discounted at a 3% rate annually and are presented in 2015 U.S. dollars. RESULTS: In the base case, sacubitril-valsartan, compared with enalapril, was more costly ($60,391 vs. $21,758) and more effective (6.49 vs. 5.74 QALYs) over a lifetime. The cost-effectiveness of sacubitril-valsartan was highly dependent on duration of treatment, ranging from $249,411 per QALY at 3 years to $50,959 per QALY gained over a lifetime. CONCLUSIONS: Sacubitril-valsartan may be a cost-effective treatment option depending on the willingness-to-pay threshold. Future investigations should incorporate real-world evidence with sacubitril-valsartan to further inform decision making.