Factors associated with longer survival among older medicare patients after diagnosis of supratentorial primary brain malignancies: a retrospective cohort study.

OBJECTIVES: Despite recent advances, the prognosis for primary malignant brain tumors (PMBTs) remains poor. Some commonly prescribed medications may exhibit anti-tumor properties in various cancers, and neurodegenerative diseases may activate pathways that counteract gliomagenesis. Our study is focused on determining if there is a correlation between the use of metformin, beta-blockers, angiotensin converting enzyme inhibitors (ACEIs), and angiotensin receptor blockers (ARBs), or the presence of Parkinson's disease (PD), and the survival rates following a diagnosis of a PMBT. METHODS: This analysis of the 100% Texas Medicare Database identified patients aged 66+ years diagnosed with a supratentorial PMBT from 2014-2017. Cox proportional hazards regression was employed to analyze survival following diagnosis and associations of survival with surgical intervention, radiation, PD diagnosis, and prescription of metformin, beta-blockers, ACEIs, or ARBs. RESULTS: There were 1,943 patients who met study criteria, and the median age was 74 years. When medication utilization was stratified by none, pre-diagnosis only, post-diagnosis only, or both pre- and post-diagnosis (continuous), continuous utilization of metformin, beta-blockers, ACEIs, or ARBs was associated with prolonged survival compared to no utilization (hazard ratio [HR]:0.45, 95% CI:0.33-0.62; HR:0.71. 95% CI:0.59-0.86; HR:0.59, 95% CI:0.48-0.72; and HR:0.45, 95% CI:0.35-0.58 respectively). PD was also associated with longer survival (HR:0.59-0.63 across the four models). DISCUSSION: Our study suggests that metformin, beta-blockers, ACEIs, ARBs, and comorbid PD are associated with a survival benefit among geriatric Medicare patients with supratentorial PMBTs.

Evaluating Provider and Pharmacy Discordance in Potential Calcium Channel Blocker-Loop Diuretic Prescribing Cascade.

BACKGROUND: Prescribing cascades occur when a drug-induced adverse event is treated with a new medication. Identifying clinical scenarios in which prescribing cascades are more likely to occur may help determine ways to prevent prescribing cascades. OBJECTIVE: To understand the extent to which discordant providers and discordant pharmacies contribute to the dihydropyridine calcium channel blocker (DH CCB)-loop diuretic prescribing cascade. STUDY POPULATION AND DESIGN: A retrospective cohort study using Medicare Fee-For-Service data (2011-2018) of adults aged ≥ 66 years. EXPOSURES: Patients who initiated DH CCB with subsequent initiation of loop diuretic (DH CCB-loop diuretic dyad) within 90 days or patients who initiated angiotensin-converting enzyme inhibitor (ACEI)/angiotensin receptor blocker (ARB) with subsequent initiation of a loop diuretic (ACEI/ARB-loop diuretic dyad; control). MAIN OUTCOMES: The primary outcomes were provider and pharmacy discordance for prescribing cascades and control drug pairs. Baseline clinical and socio-demographic characteristics were balanced using inverse probability of treatment weighting with propensity scores. RESULTS:  Overall, we identified 1987 DH CCB-loop diuretic dyads and 3148 ACEI/ARB-loop diuretic dyads. Discordant providers occurred in 64% of DH CCB-loop diuretic dyads and 55% of ACEI/ARB-loop diuretic dyads, while discordant pharmacies occurred in 19% of DH CCB-loop diuretic dyads and 16% of ACEI/ARB-loop diuretic dyads. After adjustment, the risk of having discordant providers was 20% {Relative Risk (RR) 1.20 [95% confidence interval (CI), 1.14-1.26]} higher in the DH CCB-loop diuretic dyad compared with the ACEI/ARB-loop diuretic dyad. Moreover, pharmacy discordance was 17% (RR 1.17 [95% CI 1.02-1.33]) higher. CONCLUSION: Our findings suggest that discordant providers and discordant pharmacies were more commonly involved in the potential prescribing cascade when compared with a similar control dyad of medications. Opportunities for enhanced care coordination and medication reconciliation should be explored to prevent unnecessary polypharmacy.

Medical Therapy Before, During and After Hospitalization in Medicare Beneficiaries With Heart Failure and Diabetes: Get With The Guidelines - Heart Failure Registry.

BACKGROUND: Patients hospitalized with heart failure (HF) and diabetes mellitus (DM) are at risk for worsening clinical status. Little is known about the frequency of therapeutic changes during hospitalization. We characterized the use of medical therapies before, during and after hospitalization in patients with HF and DM. METHODS: We identified Medicare beneficiaries in Get With The Guidelines-Heart Failure (GWTG-HF) hospitalized between July 2014 and September 2019 with Part D prescription coverage. We evaluated trends in the use of 7 classes of antihyperglycemic therapies (metformin, sulfonylureas, GLP-1RA, SGLT2-inhibitors, DPP-4 inhibitors, thiazolidinediones, and insulins) and 4 classes of HF therapies (evidence-based ß-blockers, ACEi or ARB, MRA, and ARNI). Medication fills were assessed at 6 and 3 months before hospitalization, at hospital discharge and at 3 months post-discharge. RESULTS: Among 35,165 Medicare beneficiaries, the median age was 77 years, 54% were women, and 76% were white; 11,660 (33%) had HFrEF (LVEF ≤ 40%), 3700 (11%) had HFmrEF (LVEF 41%-49%), and 19,805 (56%) had HFpEF (LVEF ≥ 50%). Overall, insulin was the most commonly prescribed antihyperglycemic after HF hospitalization (n = 12,919, 37%), followed by metformin (n = 7460, 21%) and sulfonylureas (n = 7030, 20%). GLP-1RA (n = 700, 2.0%) and SGLT2i (n = 287, 1.0%) use was low and did not improve over time. In patients with HFrEF, evidence-based beta-blocker, RASi, MRA, and ARNI fills during the 6 months preceding HF hospitalization were 63%, 62%, 19%, and 4%, respectively. Fills initially declined prior to hospitalization, but then rose from 3 months before hospitalization to discharge (beta-blocker: 56%-82%; RASi: 51%-57%, MRA: 15%-28%, ARNI: 3%-6%, triple therapy: 8%-20%; P < 0.01 for all). Prescription rates 3 months after hospitalization were similar to those at hospital discharge. CONCLUSIONS: In-hospital optimization of medical therapy in patients with HF and DM is common in participating hospitals of a large US quality improvement registry.

Trajectories of adherence to ACEI/ARB medications following a motivational interviewing intervention among Medicare Advantage beneficiaries in Texas.

OBJECTIVES: To assess the impact of student telephone motivational interviewing intervention on angiotensin-converting enzyme inhibitors/angiotensin-receptor blockers (ACEI/ARBs) adherence trajectories and identify predictors of each trajectory. METHODS: The intervention group included continuously enrolled Medicare Advantage Plan patients non-adherent to ACEI/ARBs vs the control group (1:2 ratio). The intervention was tailored by pre-intervention trajectories and included an initial and five follow-up calls. Adherence was measured 6 months after initial calls using the proportion of days covered (PDC). Monthly PDCs were integrated into a group-based trajectory model and categorized patients into 4-groups. A multinomial logistic regression model was used to evaluate trajectory predictors. RESULTS: The study comprised 240 intervention patients and 480 controls with four trajectories: adherent trajectory 44.2%, gradual improvement in adherence 13.4%, slow decline in adherence 24.1%, and discontinuation 18.3%. Patients with the intervention were less likely to experience a slow decline in adherence than controls (OR: 0.627 [0.401-0.981]). Patients with specialty prescribers' visits, ≥ 1 previous hospitalization, rapid decline in adherence as pre-intervention trajectory, and higher CMS risk score were associated with discontinuation trajectory. CONCLUSION: Intervention patients vs controls had a lower likelihood of following a slow decline in adherence pattern. PRACTICE IMPLICATIONS: This study underscores the importance of individualized interventions and the association between past adherence patterns and post-intervention trajectories.

Health and Economic Evaluation of Sacubitril-Valsartan for Heart Failure Management.

Importance: The US Food and Drug Administration expanded labeling of sacubitril-valsartan from the treatment of patients with chronic heart failure (HF) with reduced ejection fraction (EF) to all patients with HF, noting the greatest benefits in those with below-normal EF. However, the upper bound of below normal is not clearly defined, and value determinations across a broader EF range are unknown. Objective: To estimate the cost-effectiveness of sacubitril-valsartan vs renin-angiotensin system inhibitors (RASis) across various upper-level cutoffs of EF. Design, Setting, and Participants: This economic evaluation included participant-level data from the PARADIGM-HF (Prospective Comparison of ARNI With ACEI to Determine Impact on Global Mortality and Morbidity in Heart Failure) and the PARAGON-HF (Prospective Comparison of ARNi with ARB Global Outcomes in HF With Preserved Ejection Fraction) trials. PARADIGM-HF was conducted between 2009 and 2014, PARAGON-HF was conducted between 2014 and 2019, and this analysis was conducted between 2021 and 2023. Main Outcomes and Measures: A 5-state Markov model used risk reductions for all-cause mortality and HF hospitalization from PARADIGM-HF and PARAGON-HF. Quality-of-life differences were estimated from EuroQol-5D scores. Hospitalization and medication costs were obtained from published national sources; the wholesale acquisition cost of sacubitril-valsartan was $7092 per year. Risk estimates and treatment effects were generated in consecutive 5% EF increments up to 60% and applied to an EF distribution of US patients with HF from the Get With the Guidelines-Heart Failure registry. The base case included a lifetime horizon from a health care sector perspective. Incremental cost-effectiveness ratios (ICERs) were estimated at EFs of 60% or less (base case) and at various upper-level EF cutoffs. Results: Among 13 264 total patients whose data were analyzed, for those with EFs of 60% or less, sacubitril-valsartan was projected to add 0.53 quality-adjusted life-years (QALYs) at an incremental lifetime cost of $40 892 compared with RASi, yielding an ICER of $76 852 per QALY. In a probabilistic sensitivity analysis, 95% of the values of the ICER occurred between $71 516 and $82 970 per QALY. Among patients with chronic HF and an EF of 60% or less, treatment with sacubitril-valsartan vs RASis would be at least of economic intermediate value (ICER <$180 000 per QALY) at a sacubitril-valsartan cost of $10 242 or less per year, of high economic value (ICER <$60 000 per QALY) at a cost of $3673 or less per year, and cost-saving at a cost of $338 or less per year. The ICERs were $67 331 per QALY, $59 614 per QALY, and $56 786 per QALY at EFs of 55% or less, 50% or less, and 45% or less, respectively. Treatment with sacubitril-valsartan in only those with EFs of 45% or greater (up to ≤60%) yielded an ICER of $127 172 per QALY gained; treatment was more cost-effective in those at the lower end of this range (ICER of $100 388 per QALY gained for those with EFs of 45%-55%; ICER of $84 291 per QALY gained for those with EFs of 45%-50%). Conclusions and Relevance: Cost-effectiveness modeling provided an ICER for treatment with sacubitril-valsartan vs RASis consistent with high economic value for patients with reduced and mildly reduced EFs (≤50%) and at least intermediate value at the current undiscounted wholesale acquisition cost price at an EF of 60% or less. Treatment was more cost-effective at lower EF ranges. These findings may have implications for coverage decisions and value assessments in contemporary clinical practice guidelines.

Comparing Cardiovascular Outcomes and Costs of Perindopril-, Enalapril- or Losartan-Based Antihypertensive Regimens in South Africa: Real-World Medical Claims Database Analysis.

INTRODUCTION: Differences in class or molecule-specific effects between renin-angiotensin-aldosterone system (RAAS) inhibitors have not been conclusively demonstrated. This study used South African data to assess clinical and cost outcomes of antihypertensive therapy with the three most common RAAS inhibitors: perindopril, losartan and enalapril. METHODS: Using a large, South African private health insurance claims database, we identified patients with a hypertension diagnosis in January 2015 receiving standard doses of perindopril, enalapril or losartan, alone or in combination with other agents. From claims over the subsequent 5 years, we calculated the risk-adjusted rate of the composite primary outcome of myocardial infarction, ischaemic heart disease, heart failure or stroke; rate of all-cause mortality; and costs per life per month (PLPM), with adjustments based on demographic characteristics, healthcare plan and comorbidity. RESULTS: Overall, 32,857 individuals received perindopril, 16,693 losartan and 13,939 enalapril. Perindopril-based regimens were associated with a significantly lower primary outcome rate (205 per 1000 patients over 5 years) versus losartan (221; P < 0.0001) or enalapril (223; P < 0.0001). The risk-adjusted all-cause mortality rate was lower with perindopril than enalapril (100 vs. 139 deaths per 1000 patients over 5 years; P = 0.007), but not losartan (100 vs. 94; P = 0.650). Mean (95% confidence interval) overall risk-adjusted cost PLPM was Rands (ZAR) 1342 (87-8973) for perindopril, ZAR 1466 (104-9365) for losartan (P = 0.0044) and ZAR 1540 (77-10,546) for enalapril (P = 0.0003). CONCLUSION: In South African individuals with private health insurance, a perindopril-based antihypertensive regimen provided better clinical and cost outcomes compared with other regimens.

Comparative Outcomes of Sacubitril/Valsartan Use After Hospitalization for Heart Failure Among Medicare Beneficiaries Naïve to Renin-Angiotensin System Inhibitors.

Sacubitril/valsartan improves outcomes in patients with heart failure with reduced ejection fraction (HFrEF) compared with angiotensin-converting enzyme inhibitors (ACEis). However, data on postdischarge outcomes in renin-angiotensin system inhibitor (RASi)-naïve patients are limited. We included Medicare beneficiaries aged ≥65 years who were hospitalized for HFrEF in the Get With The Guidelines-Heart Failure registry between October 2015 and June 2019, had part D prescription coverage, and were not on RASi therapy during the 6 months before hospital admission. We examined the associations between sacubitril/valsartan prescription at hospital discharge and outcomes at 30 days and 1 year after discharge using overlap-weighted median regression and Cox proportional hazards models. The end points included "home time" (defined as days alive and out of any health care institution), mortality, and rehospitalization. Among 3,572 patients with HFrEF and who are naïve to RASi therapy, at discharge, 290 (8.1%) were prescribed sacubitril/valsartan and 1,390 (38.9%) were prescribed ACEis and angiotensin receptor blockers. After adjusting for baseline characteristics, patients prescribed sacubitril/valsartan had a longer median home time (parameter estimate 27.0 days, 95% confidence interval [CI] 12.40 to 41.6, p <0.001) and lower all-cause mortality (hazard ratio [HR] 0.74, 95% CI 0.61 to 0.91, p = 0.004) at 1 year than patients not prescribed sacubitril/valsartan. The prescription of sacubitril/valsartan was not significantly associated with all-cause rehospitalization (HR 0.87, 95% CI 0.74 to 1.03, p = 0.10) or heart failure rehospitalization (HR 0.87, 95% CI 0.70 to 1.07, p = 0.19). In a restricted comparison of patients discharged on sacubitril/valsartan versus ACEis and angiotensin receptor blockers, there were no significant differences in the outcomes. In conclusion, in this contemporary population of RASi-naïve patients with HFrEF from routine clinical practice, compared with not initiating, the initiation of sacubitril/valsartan at discharge was associated with longer home time and improvements in overall survival.

Cost-Effectiveness of Quadruple Therapy in Management of Heart Failure With Reduced Ejection Fraction in the United States.

BACKGROUND: The 2022 clinical guidelines for management of heart failure with reduced ejection fraction call for quadruple therapy. Quadruple therapy consists of an angiotensin receptor-neprilysin inhibitor (ARNi), sodium-glucose cotransporter-2 inhibitor (SGLT2i), mineralocorticoid receptor antagonist, and beta blocker. The ARNi and sodium-glucose cotransporter-2 inhibitor are newer additions to standard of care with the ARNi replacing ACE (angiotensin-converting enzyme) inhibitors and angiotensin II receptor blockers. METHODS: We investigate the cost-effectiveness of sequentially adding the SGLT2i and ARNi to form quadruple therapy as compared with the previous standard of care with ACE inhibitor/mineralocorticoid receptor antagonist/beta blocker. Using a 2-stage Markov model, we projected the expected lifetime discounted costs and quality-adjusted life years (QALYs) of a simulated cohort of US patients who underwent each treatment option and calculated incremental cost-effectiveness ratios. We assessed incremental cost-effectiveness ratios using criteria for health care value (<$50 000/quality-adjusted life year [QALY] indicating high-value, $50 000-150 000/QALY indicating intermediate value, and >$150 000/QALY indicating low-value) and a standard $100 000/QALY cost-effectiveness threshold. RESULTS: Compared with the previous standard of care, the SGLT2i addition had an incremental cost-effectiveness ratio of $73 000/QALY and weakly dominated the ARNi addition. The addition of both the ARNi and SGLT2i for quadruple therapy offered 0.68 additional discounted QALYs over the SGLT2i addition alone at a lifetime discounted cost of $66 700, resulting in an incremental cost-effectiveness ratio of $98 500/QALY. In sensitivity analysis varying drug prices, the incremental cost-effectiveness ratio for quadruple therapy ranged from $73 500/QALY using prices available to the US Department of Veterans Affairs to $110 000/QALY using drug list prices. CONCLUSIONS: While quadruple therapy offers intermediate value, it is borderline cost effective compared with adding the SGLT2i alone to previous standard of care. Thus, its cost-effectiveness is sensitive to a payer's ability to negotiate discounts off the increasing list prices for ARNI and SGLT2is. The demonstrated benefits of ARNi and SGLT2is should be weighed against their high prices in payer and policy considerations.

Great Sustainability Results From Appropriate Antihypertensive Therapy.

Cardiovascular diseases are emerging as a major cause of death and hospitalization in the Western world. For many years, a number of medicines have been placed on the market, in well-established and safe use for antihypertensive therapy. The various classes of antihypertensives in established use include, ACE inhibitors, as monotherapy or in combination with diuretics or calcium antagonists, sartans, calcium antagonists, beta blockers, and diuretics. Among these medicines classes there are differences in mechanism of action, efficacy in reducing blood pression, tolerability, and cost. In fact, there are wide differences in the monthly cost of therapy within each class and among the classes themselves. In this analysis we describe an example about the prescribing trends of antihypertensive drugs at a European sample represented by an Italian health care company of about 1 million inhabitants. Aspects of pharmacoeconomics, pharmacoutilization, and pharmacological differences are described.

Using Sacubitril/Valsartan to Decrease Health care Costs in Population Health Patients.

Value-based care is the foundation of population health. The Health care Economic Efficiency Ratio (HEERO) scoring system is a promising new tool to measure the cost benefits of care in our Accountable Care Organization. HEERO score compares actual costs spent (utilizing insurance claims) and expected costs spent (estimated using the Centers for Medicare/Medicaid Services Risk score). Scores <1 suggest economic benefit. Sacubitril/valsartan has been shown to decrease readmissions for patients with heart failure (HF) and decrease health care costs. We explored the utility of sacubitril/valsartan in reducing HEERO scores and decreasing overall health care expenditure in patients with HF. Patients with HF in the population health cohort were enrolled. HEERO score was calculated for patients taking sacubitril/valsartan and other HF medications at 3-month intervals up to a year. We compared the average and total health care expenditure and inpatient days for patients on sacubitril/valsartan, spironolactone, ß blocker (BB) along with spironolactone, BB and angiotensin-converting enzyme inhibitor/angiotensin receptor blocker. For patients on sacubitril/valsartan, HEERO scores and inpatient days decreased (decreased health care expenditure) as the number of days of utilization increased (p <0.0001). In total, 270+ days of sacubitril/valsartan decreased health care costs by 22%. This cost reduction was mainly attributed to decreased inpatient days. Additionally, the combination of sacubitril/valsartan, spironolactone, and BB showed decreased HEERO score and inpatient days compared with spironolactone, BB and angiotensin-converting enzyme inhibitor/angiotensin receptor blocker in male patients. Sacubitril/valsartan use beyond 270 days resulted in decreased health care expenditure in a population health cohort compared with other HF medications. This economic benefit is achieved through the reduction in hospitalizations. Sacubitril/valsartan is an integral part of value-based care providing high-value, cost-effective care, and bolstering the economic wellbeing of patient care. Payor sources should consider this in subsidizing the cost of the medicine.

Economic Evaluations of Guideline-Directed Medical Therapies for Heart Failure With Reduced Ejection Fraction: A Systematic Review.

OBJECTIVES: Decision-analytic models (DAMs) with varying structures and assumptions have been applied in economic evaluations (EEs) to assist decision making for heart failure with reduced ejection fraction (HFrEF) therapeutics. This systematic review aimed to summarize and critically appraise the EEs of guideline-directed medical therapies (GDMTs) for HFrEF. METHODS: A systematic search of English articles and gray literature, published from January 2010, was performed on databases including MEDLINE, Embase, Scopus, NHSEED, health technology assessment, Cochrane Library, etc. The included studies were EEs with DAMs that compared the costs and outcomes of angiotensin-converting enzyme inhibitors, angiotensin-receptor blockers, angiotensin-receptor neprilysin inhibitors, beta-blockers, mineralocorticoid-receptor agonists, and sodium-glucose cotransporter-2 inhibitors. The study quality was evaluated using the Bias in Economic Evaluation (ECOBIAS) 2015 checklist and Consolidated Health Economic Evaluation Reporting Standards (CHEERS) 2022 checklists. RESULTS: A total of 59 EEs were included. Markov model, with a lifetime horizon and a monthly cycle length, was most commonly used in evaluating GDMTs for HFrEF. Most EEs conducted in the high-income countries demonstrated that novel GDMTs for HFrEF were cost-effective compared with the standard of care, with the standardized median incremental cost-effectiveness ratio (ICER) of $21 361/quality-adjusted life-year. The key factors influencing ICERs and study conclusions included model structures, input parameters, clinical heterogeneity, and country-specific willingness-to-pay threshold. CONCLUSIONS: Novel GDMTs were cost-effective compared with the standard of care. Given the heterogeneity of the DAMs and ICERs, alongside variations in willingness-to-pay thresholds across countries, there is a need to conduct country-specific EEs, particularly in low- and middle-income countries, using model structures that are coherent with the local decision context.

Worsening of chronic heart failure: definition, epidemiology, management and prevention. A clinical consensus statement by the Heart Failure Association of the European Society of Cardiology.

Episodes of worsening symptoms and signs characterize the clinical course of patients with chronic heart failure (HF). These events are associated with poorer quality of life, increased risks of hospitalization and death and are a major burden on healthcare resources. They usually require diuretic therapy, either administered intravenously or by escalation of oral doses or with combinations of different diuretic classes. Additional treatments may also have a major role, including initiation of guideline-recommended medical therapy (GRMT). Hospital admission is often necessary but treatment in the emergency service or in outpatient clinics or by primary care physicians has become increasingly used. Prevention of first and recurring episodes of worsening HF is an essential component of HF treatment and this may be achieved through early and rapid administration of GRMT. The aim of the present clinical consensus statement by the Heart Failure Association of the European Society of Cardiology is to provide an update on the definition, clinical characteristics, management and prevention of worsening HF in clinical practice.

Renin-Angiotensin Inhibition and Outcomes in HFrEF and Advanced Kidney Disease.

BACKGROUND: Renin-angiotensin system inhibitors improve outcomes in patients with heart failure with reduced ejection fraction (HFrEF). However, less is known about their effectiveness in patients with HFrEF and advanced kidney disease. METHODS: In the Medicare-linked Organized Program to Initiate Lifesaving Treatment in Hospitalized Patients with Heart Failure (OPTIMIZE-HF), 1582 patients with HFrEF (ejection fraction ≤40%) had advanced kidney disease (estimated glomerular filtration rate <30 mL/min/1.73 m2). Of these, 829 were not receiving angiotensin-converting enzyme (ACE) inhibitors or angiotensin receptor blockers (ARBs) prior to admission, of whom 214 were initiated on these drugs prior to discharge. We calculated propensity scores for receipt of these drugs for each of the 829 patients and assembled a matched cohort of 388 patients, balanced on 47 baseline characteristics (mean age 78 years; 52% women; 10% African American; 73% receiving beta-blockers). Hazard ratios (HR) and 95% confidence intervals (CI) were estimated comparing 2-year outcomes in 194 patients initiated on ACE inhibitors or ARBs to 194 patients not initiated on those drugs. RESULTS: The combined endpoint of heart failure readmission or all-cause mortality occurred in 79% and 84% of patients initiated and not initiated on ACE inhibitors or ARBs, respectively (HR associated with initiation, 0.79; 95% CI, 0.63-0.98). Respective HRs (95% CI) for the individual endpoints of - Respective HRs (95% CI) for the individual endpoints of all-cause mortality and heart failure readmission were 0.81 (0.63-1.03) and 0.63 (0.47-0.85). CONCLUSIONS: The findings from our study add new information to the body of cumulative evidence that suggest that renin-angiotensin system inhibitors may improve clinical outcomes in patients with HFrEF and advanced kidney disease. These hypothesis-generating findings need to be replicated in contemporary patients.

Relationship Between Medical Therapy, Long-Term Care Insurance, and Comorbidity in Elderly Patients With Heart Failure With Systolic Dysfunction.

BACKGROUND: Although guideline-directed medical therapy (GDMT), including ß-blockers, angiotensin-converting enzyme inhibitors (ACEi)/angiotensin receptor blockers (ARBs), and mineralocorticoid receptor antagonists (MRAs), improves survival and quality of life, most patients with heart failure with reduced (HFrEF) and mildly reduced (HFmrEF) ejection fraction are treated with inadequate medications. We investigated the prescription patterns of GDMT in elderly patients with HFrEF and HFmrEF and their characteristics, including the certification of long-term care insurance (LTCI), which represents frailty and disability.Methods and Results: This retrospective cross-sectional study analyzed 1,296 elderly patients with symptomatic HFrEF and HFmrEF with diuretic use (median age 78 years; 63.8% male; median left ventricular ejection fraction 40%). Prescription rates of GDMT were inadequate (ACEi, ARBs, ß-blockers, and MRAs: 27.0%, 30.1%, 54.1%, and 41.9%, respectively). LTCI certification was independently associated with reduced prescription of all medications (ACEi/ARB: odds ratio [OR] 0.591, 95% confidence interval [CI] 0.449-0.778, P=0.001; ß-blockers: OR 0.698, 95% CI 0.529-0.920, P<0.001; MRAs: OR 0.743, 95% CI 0.560-0.985, P=0.052). Patients with LTCI certification also had a high prevalence of polypharmacy and prescription of diuretics. CONCLUSIONS: Vulnerable patients with LTCI may be an explanation for the challenges in implementing GDMT, and communicating is required for favorable heart failure care in this population.

Cost-Effectiveness of Comprehensive Quadruple Therapy for Heart Failure With Reduced Ejection Fraction.

BACKGROUND: Heart failure with reduced ejection fraction (HFrEF) is one of the most costly and deadly chronic disease states. The cost effectiveness of a comprehensive quadruple therapy regimen for HFrEF has not been studied. OBJECTIVES: The authors sought to determine the cost-effectiveness of quadruple therapy comprised of beta-blockers, mineralocorticoid receptor antagonists, angiotensin receptor-neprilysin inhibitors, and sodium glucose cotransporter-2 inhibitors vs regimens composed of only beta-blockers, angiotensin-converting enzyme inhibitors, and mineralocorticoid receptor antagonists (triple therapy), and angiotensin-converting enzyme inhibitors and beta-blockers (double therapy). METHODS: Using a 2-state Markov model, the authors performed a cost-effectiveness study using simulated populations of 1,000 patients with HFrEF based on the participants in the PARADIGM-HF (Prospective comparison of ARNI with ACEI to Determine Impact on Global Mortality and morbidity in Heart Failure) trial and compared them by treatment strategy (quadruple therapy vs triple and double therapy) from a United States health care system perspective. The authors also performed 10,000 probabilistic simulations. RESULTS: Treatment with quadruple therapy resulted in an increase of 1.73 and 2.87 life-years compared with triple therapy and double therapy, respectively, and an increase in quality-adjusted life-years of 1.12 and 1.85 years, respectively. The incremental cost-effectiveness ratios of quadruple therapy vs triple therapy and double therapy were $81,000 and $51,081, respectively. In 91.7% and 99.9% of probabilistic simulations quadruple therapy had an incremental cost-effectiveness ratio of <$150,000 compared with triple therapy and double therapy, respectively. CONCLUSIONS: At current pricing, the use of quadruple therapy in patients with HFrEF was cost effective compared with triple therapy and double therapy. These findings highlight the need for improved access and optimal implementation of comprehensive quadruple therapy in eligible patients with HFrEF.

A Motivational Interviewing Intervention to Improve Adherence to ACEIs/ARBs among Nonadherent Older Adults with Comorbid Hypertension and Diabetes.

BACKGROUND: Hypertension and diabetes mellitus are independent risk factors for cardiovascular diseases. Due to the cardioprotective nature of angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin II receptor blockers (ARBs), they are recommended for patients with comorbid hypertension and diabetes. However, poor adherence to ACEIs/ARBs among older adults is a major public health concern. This study aimed to assess the effectiveness of a telephonic motivational interviewing (MI) intervention conducted by pharmacy students among a nonadherent older population (≥ 65 years old) with diabetes and hypertension. METHODS: Patients continuously enrolled in a Medicare Advantage Plan who received an ACEI/ARB prescription between July 2017 and December 2017 were identified. Group-based trajectory modeling (GBTM) was used to identify distinct patterns of ACEI/ARB adherence during the 1-year baseline period: adherent, gaps in adherence, gradual decline, and rapid decline in adherence. Patients from the three nonadherent trajectories were randomized into MI intervention or control group. The intervention consisted of an initial call and five follow-up calls administered by MI-trained pharmacy students and tailored to the baseline ACEI/ARB adherence trajectories. The primary outcome was adherence to ACEI/ARB during the 6- and 12-month periods post-MI implementation. The secondary outcome was discontinuation, defined as no refills for ACEI/ARB during the 6- and 12-month periods post-MI implementation. Multivariable regression analyses examined the impact of MI intervention on ACEI/ARB adherence and discontinuation while adjusting for baseline covariates. RESULTS: A total of 240 patients in the intervention group and 480 patients as randomly selected controls were included in this study. At 6 months, patients receiving the MI intervention had significantly better adherence (ß = 0.06; p = 0.03) compared with the controls. Linear and logistic regression models also showed patients in the intervention group were more likely to be adherent than controls within 12 months of intervention implementation (ß = 0.06; p = 0.02 and OR: 1.46; 95% CI 1.05-2.04, respectively). MI intervention did not have any significant impact on the ACEI/ARB discontinuation. CONCLUSION: Patients who received the MI intervention were more likely to be adherent at 6 and 12 months following the intervention initiation, despite gaps in the follow-up calls due to COVID-19. Pharmacist-led MI intervention is an effective behavioral strategy to improve medication adherence among older adults and tailoring the intervention to past adherence patterns may enhance the intervention effectiveness. This study was registered with the United States National Institutes of Health (ClinicalTrials.gov identifier NCT03985098).

Initial Antihypertensive Regimens in Newly Treated Patients: Real World Evidence From the OneFlorida+ Clinical Research Network.

Background Knowledge of real-world antihypertensive use is limited to prevalent hypertension, limiting our understanding of how treatment evolves and its contribution to persistently poor blood pressure control. We sought to characterize antihypertensive initiation among new users. Methods and Results Using Medicaid and Medicare data from the OneFlorida+ Clinical Research Consortium, we identified new users of ≥1 first-line antihypertensives (angiotensin-converting enzyme inhibitor, calcium channel blocker, angiotensin receptor blocker, thiazide diuretic, or ß-blocker) between 2013 and 2021 among adults with diagnosed hypertension, and no antihypertensive fill during the prior 12 months. We evaluated initial antihypertensive regimens by class and drug overall and across study years and examined variation in antihypertensive initiation across demographics (sex, race, and ethnicity) and comorbidity (chronic kidney disease, diabetes, and atherosclerotic cardiovascular disease). We identified 143 054 patients initiating 188 995 antihypertensives (75% monotherapy; 25% combination therapy), with mean age 59 years and 57% of whom were women. The most commonly initiated antihypertensive class overall was angiotensin-converting enzyme inhibitors (39%) followed by ß-blockers (31%), calcium channel blockers (24%), thiazides (19%), and angiotensin receptor blockers (11%). With the exception of ß-blockers, a single drug accounted for ≥75% of use of each class. ß-blocker use decreased (35%-26%), and calcium channel blocker use increased (24%-28%) over the study period, while initiation of most other classes remained relatively stable. We also observed significant differences in antihypertensive selection across demographic and comorbidity strata. Conclusions These findings indicate that substantial variation exists in initial antihypertensive prescribing, and there remain significant gaps between current guideline recommendations and real-world implementation in early hypertension care.

The Utilization, Expenditure, and Price of Angiotensin-Converting Enzyme Inhibitors and Angiotensin Receptor Blockers in the US Medicaid Programs: Trends Over a 31 Year Period.

BACKGROUND: Angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) are used for several indications including hypertension. Our aim is to evaluate the utilization, expenditure, and drug price of ACEIs and ARBs in the US Medicaid population. METHODS: A retrospective descriptive trend analysis was conducted using Medicaid State Drug Utilization outpatient pharmacy summary files managed by the Centers for Medicare and Medicaid Services from 1991 to 2021. Study drugs included ACEIs (e.g., captopril) and ARBs (e.g., losartan). Annual reimbursement and utilization were calculated for both classes. The average reimbursement per prescription was calculated as a proxy for drug prices. Market share competition between ACEIs and ARBs was analyzed over time. RESULTS: ACEI and ARB utilization rose by 25% from 1991 to 2021. Brand ACEIs utilization peaked in 2002 with 28 million prescriptions while brand ARBs utilization continued to increase until 2005 with over 23 million prescriptions. However, generic products took the lead and exceeded brand ACEI and ARB utilization in 2006 and 2012 respectively. Medicaid spent over $ 33.7 billion on ACEIs and ARBs over 31-year. Brand ACEIs and ARBs average prices increased sharply to $8,104 and $6,908 respectively in 2021. The total prescription market share for ACEIs was 68% compared to 32% of ARBs over the entire study. CONCLUSION: ACEIs and ARBs utilization increased over the last 31 years. Brand utilization switched over to generic resulting in less reimbursement. The average prices of brand ACEIs and ARBs continue to increase even after generics were introduced to the market.

Cost-Effectiveness of Sacubitril-Valsartan Compared to Angiotensin-Converting Enzyme Inhibitors in Patients With Heart Failure With Reduced Ejection Fraction.

Objectives: The goal of this study was to compare cost-effectiveness of sacubitril/valsartan with angiotensin-converting enzyme (ACE) inhibitors for treating chronic heart failure patients with reduced ejection fraction (HFrEF) from the published articles and explore the methodology applied in the studies. Methods: Systematic research was conducted in February 2021 using PubMed, Cochrane, and EBSCO. A combination of MeSH terms of "cost-effectiveness analysis," "heart failure with reduced ejection fraction," "sacubitril valsartan," and "angiotensin converting enzyme inhibitor" was employed. The review selected for articles published in the last five years in English. Results: A total of 15 studies were included in this review. We found that these studies had been conducted in 12 different countries. The United States had the greatest number of publications (5), followed by the Netherlands (2). The study method most used was the Markov decision model (73%). Almost all studies produced ICERs and QALYs that were numerically high. Conclusions: The use of sacubitril/valsartan associates with longer life expectancy and incremental cost-effectiveness ratio than angiotensin-converting enzyme inhibitors.