Cost-effectiveness of sacubitril/valsartan versus enalapril in patients with heart failure and reduced ejection fraction

Background: Sacubitril/valsartan reduces cardiovascular death and hospitalizations for heart failure (HF). However, decision-makers need to determine whether its benefits are worth the additional costs, given the low-cost generic status of traditional standard of care.

Aims: To evaluate the cost-effectiveness of sacubitril/valsartan compared to enalapril in patients with HF and reduced ejection fraction, from the Singapore healthcare payer perspective.

Methods: A Markov model was developed to project clinical and economic outcomes of sacubitril/valsartan vs enalapril for 66-year-old patients with HF over 10 years. Key health states included New York Heart Association classes I–IV and deaths; patients in each state incurred a monthly risk of hospitalization for HF and cardiovascular death. Sacubitril/valsartan benefits were modeled by applying the hazard ratios (HRs) in PARADIGM-HF trial to baseline probabilities. Primary model outcomes were total and incremental costs and quality-adjusted life years (QALYs) and the incremental cost-effectiveness ratio (ICER) for sacubitril/valsartan relative to enalapril

Results: Compared to enalapril, sacubitril/valsartan was associated with an ICER of SGD 74,592 (USD 55,198) per QALY gained. A major driver of cost-effectiveness was the cardiovascular mortality benefit of sacubitril/valsartan. The uncertainty of this treatment benefit in the Asian sub-group was tested in sensitivity analyses using a HR of 1 as an upper limit, where the ICERs ranged from SGD 41,019 (USD 30,354) to SGD 1,447,103 (USD 1,070,856) per QALY gained. Probabilistic sensitivity analyses showed the probability of sacubitril/valsartan being cost-effective was below 1%, 12%, and 71% at SGD 20,000, SGD 50,000, and SGD 100,000 per QALY gained, respectively.

Conclusions: At the current daily price sacubitril/valsartan may not represent good value for limited healthcare dollars compared to enalapril in reducing cardiovascular morbidity and mortality in HF in the Singapore healthcare setting. This study highlights the cost-benefit trade-off that healthcare professionals and patients face when considering therapy.     

Economic evaluation of valsartan in patients with chronic heart failure: results from Val-HeFT adapted to The Netherlands

Summary

The Valsartan Heart Failure Trial (Val-HeFT) was a multinational randomised trial of valsartan versus placebo in a total of 5,010 patients with heart failure. During the study period, valsartan resulted in significant reductions in hospitalisations due to heart failure.

The objective of this study was to evaluate the economic impact of valsartan in Dutch heart failure patients.

Resource use during Val-HeFT was multiplied by Dutch cost estimates. Mean patient follow-up was 23 months and costs for hospitalisations were €617 lower among valsartan patients. Mean total costs for valsartan and placebo patients were €8,810 and €8,441, respectively, resulting in incremental costs of €368. In patients receiving an angiotensin-converting enzyme (ACE) inhibitor but no beta-blocker, these incremental costs were even lower (€171). There were overall net savings of €1,311 in patients not receiving an ACE inhibitor at baseline.

Valsartan provides clinical benefits at modest costs in The Netherlands. In patients not receiving an ACE inhibitor at baseline, valsartan was dominant.     

Development of a health economic model to evaluate the potential benefits of optimal serum potassium management in patients with heart failure

Abstract

Aims: Patients with heart failure are at increased risk of hyperkalemia, particularly when treated with renin-angiotensin-aldosterone system inhibitor (RAASi) agents. This study developed a model to quantify the potential health and economic value associated with sustained potassium management and optimal RAASi therapy in heart failure patients.

Materials and methods: A patient-level, fixed-time increment stochastic simulation model was designed to characterize the progression of heart failure through New York Heart Association functional classes, and predict associations between serum potassium levels, RAASi use, and consequent long-term outcomes. Following internal and external validation exercises, model analyses sought to quantify the health and economic benefits of optimizing both serum potassium levels and RAASi therapy in heart failure patients. Analyses were conducted using a UK payer perspective, independent of costs and utilities related to pharmacological potassium management.

Results: Validation against multiple datasets demonstrated the predictive capability of the model. Compared to those who discontinued RAASi to manage serum potassium, patients with normokalemia and ongoing RAASi therapy benefited from longer life expectancy (+1.38 years), per-patient quality-adjusted life year gains (+0.53 QALYs), cost savings (£110), and associated net monetary benefit (£10,679 at £20,000 per QALY gained) over a lifetime horizon. The predicted value of sustained potassium management and ongoing RAASi treatment was largely driven by reduced mortality and hospitalization risks associated with optimal RAASi therapy.

Limitations: Several modeling assumptions were made to account for a current paucity of published literature; however, ongoing refinement and validation of the model will ensure its continued accuracy as the clinical landscape of hyperkalemia evolves.

Conclusions: Predictions generated by this novel modeling approach highlight the value of sustained potassium management to avoid hyperkalemia, enable RAASi therapy, and improve long-term health economic outcomes in patients with heart failure.     

Estimates of the direct and indirect cost savings associated with heart disease that could be avoided through dietary change in the United States

Aims: Diets high in saturated fat are associated with elevated risk of heart disease. This study estimates the savings in direct (medical care) costs and indirect (job absenteeism) costs in the US from reductions in heart disease associated with substituting monounsaturated fats (MUFA) for saturated fats.

Materials and methods: A four-part model of the medical care cost savings from avoided heart disease was estimated using data on 247,700 adults from the 2000–2010 Medical Expenditure Panel Survey (MEPS). The savings from reduced job absenteeism due to avoided heart disease was estimated using a zero-inflated negative binomial model of the number of annual work loss days applied to data on 164,577 adults from the MEPS.

Results: Estimated annual savings in medical care expenditures resulting from a switch from a diet high in saturated fat to a high-MUFA diet totaled ～ $25.7 billion (95% CI = $6.0–$45.4 billion) in 2010, with private insurance plans saving $7.9 billion (95% CI?=?$1.8–$14.0 billion), Medicare saving $9.4 billion (95% CI?=?$2.1–$16.7 billion), Medicaid saving $1.4 billion (95% CI?=?Aims: Diets high in saturated fat are associated with elevated risk of heart disease. This study estimates the savings in direct (medical care) costs and indirect (job absenteeism) costs in the US from reductions in heart disease associated with substituting monounsaturated fats (MUFA) for saturated fats.

Materials and methods: A four-part model of the medical care cost savings from avoided heart disease was estimated using data on 247,700 adults from the 2000–2010 Medical Expenditure Panel Survey (MEPS). The savings from reduced job absenteeism due to avoided heart disease was estimated using a zero-inflated negative binomial model of the number of annual work loss days applied to data on 164,577 adults from the MEPS.

Results: Estimated annual savings in medical care expenditures resulting from a switch from a diet high in saturated fat to a high-MUFA diet totaled ～ $25.7 billion (95% CI = $6.0–$45.4 billion) in 2010, with private insurance plans saving $7.9 billion (95% CI?=?$1.8–$14.0 billion), Medicare saving $9.4 billion (95% CI?=?$2.1–$16.7 billion), Medicaid saving $1.4 billion (95% CI?=?$0.2–$2.5 billion), and patients saving $2.2 billion (95% CI?=?$0.5–$3.8 billion). The annual savings in terms of reduced job absenteeism ranges from a lower bound of $600 million (95% CI?=?$100 million to $1.0 billion) to an upper bound of $1.2 billion (95% CI?=?$0.2–$2.1 billion) for 2010.

Limitations: The data cover only the non-institutionalized population. Decreased costs due to any decreases in the severity of heart disease are not included. Cost savings do not include any reduction in informal care at home.

Conclusions: Diets high in saturated fat impose substantial medical care costs and job absenteeism costs, and substantial savings could be achieved by substituting MUFA for saturated fat.     

Resource utilisation,charges and mortality following hospital inpatient admission for congestive heart failure among the elderly in the US

Abstract

Objectives: This study examined resource utilisation, charges and mortality among congestive heart failure (CHF) patients over the course of the first year following initial hospital discharge for CHF in the US.

Methods: The Medicare Standard Analytic Files for the years 1998 through to 2001 were used for the analysis. The study sample included patients with an inpatient hospitalisation between the 1st January 1999 and the 31st December 2000 with a primary ICD-9 diagnosis code of CHF. Statistical analysis including univariate and multivariate regression analysis were conducted.

Results: Within 1 year following initial CHF discharge, 50% of patients had at least one all-cause readmission and 20% had at least one CHF-related readmission. The mean total charges among all patients was $36,230 (sd $55,086). Of the patients 20% incurred more than $55,000 in medical charges during the year after discharge; 10% incurred charges exceeding $90,000. More than one-half of the CHF patients visited the emergency department within 3 months of hospital discharge, and within 1 year almost one-third of the CHF patients (31.4%) died.

Conclusions: The charges, morbidity and mortality associated with CHF patients are significant. Reducing these risks through more effective disease management offers the potential for substantial cost savings.     

Factors associated with increased healthcare costs in Medicare Advantage patients with type 2 diabetes enrolled in a large representative health insurance plan in the US

Abstract

Aim:

The objective of this study was to apply quantile regression (QR) methodology to a population from a large representative health insurance plan with known skewed healthcare utilization attributes, co-morbidities, and costs in order to identify predictors of increased healthcare costs. Further, this study provides comparison of the results to those obtained using ordinary least squares (OLS) regression methodology.

Methods:

Members diagnosed with Type 2 Diabetes and with 24 months of continuous enrollment were included. Baseline patient demographic, clinical, consumer/behavioural, and cost characteristics were quantified. Quantile regression was used to model the relationship between the baseline characteristics and total healthcare costs during the follow-up 12 month period.

Results:

The sample included 83,705 patients (mean age?=?70.6 years, 48% male) residing primarily in the southern US (78.1%); 81.2% of subjects were on oral-only anti-diabetic therapy. Co-morbid conditions included nephropathy (43.5%), peripheral artery disease (26.4%), and retinopathy (18.0%). Variables with the strongest relationship with costs during the follow-up period included outpatient visits, ER visits, inpatient visits, and Diabetes Complications Severity Index score during the baseline period. In the top cost quantiles, each additional glycohemoglobin (HbA1c) test was associated with cost savings ($1400 in the 98th percentile). Stage 4 and Stage 5 chronic kidney disease were associated with an incremental cost increase of $33,131 and $106,975 relative to Stage 1 or no CKD in the 98th percentile ($US).

Conclusions:

These results demonstrate that QR provides additional insight compared to traditional OLS regression modeling, and may be more useful for informing resource allocation to patients most likely to benefit from interventions. This study highlights that the impact of clinical and demographic characteristics on the economic burden of the disease vary across the continuum of healthcare costs. Understanding factors that drive costs on an individual patient level provide important insights that will help in ameliorating the clinical, humanistic, and economic burden of diabetes.     

Evaluation of costs associated with tolvaptan-mediated length-of-stay reduction among heart failure patients with hyponatremia in the US,based on the EVEREST trial

Abstract

Background:

The Efficacy of Vasopressin Antagonism in Heart Failure Outcome Study with Tolvaptan (EVEREST) trial showed that tolvaptan use improved heart failure (HF) signs and symptoms without serious adverse events.

Objective:

To evaluate the potential cost savings associated with tolvaptan usage among hospitalized hyponatremic HF patients.

Methods:

The Healthcare Cost and Utilization Project (HCUP) 2008 Nationwide Inpatient Sample (NIS) database was used to estimate hospital cost and length of stay (LOS), for diagnosis-related group (DRG) hospitalizations of adult (age ≥18 years) HF patients with complications and comorbidities or major complications and comorbidities. EVEREST trial data for patients with hyponatremia were used to estimate tolvaptan-associated LOS reductions. A cost offset model was constructed to evaluate the impact of tolvaptan on hospital cost and LOS, with univariate and multivariate Monte Carlo sensitivity analyses.

Results:

Tolvaptan use among hyponatremic EVEREST trial HF patients was associated with shorter hospital LOS than placebo patients (9.72 vs 11.44 days, respectively); 688,336 hospitalizations for HF DRGs were identified from the HCUP NIS database, with a mean LOS of 5.4 days and mean total hospital costs of $8415. Using an inpatient tolvaptan treatment duration of 4 days with a wholesale acquisition cost of $250 per day, the cost offset model estimated a LOS reduction among HF hospitalizations of 0.81 days and an estimated total cost saving of $265 per admission. Univariate and multivariate sensitivity analysis demonstrated that cost reduction associated with tolvaptan usage is consistent among variations of model variables.

Conclusions:

The estimated LOS reduction and cost savings projected by the cost offset model suggest a clinical and economic benefit to tolvaptan use in hyponatremic HF patients.

Study Limitations:

The EVEREST trial data may not generalize well to the US population. Clinical trial patient profiles and relative LOS reductions may not be applicable to real-world patient populations.     

Ultrafiltration versus diuretics for the treatment of fluid overload in patients with heart failure: a hospital cost analysis

Abstract

Background: Heart failure (HF) is a common, serious disease in the US and Europe. Patients with HF often require treatment for fluid overload, resulting in costly inpatient visits; however, limited evidence exists on the costs of alternative treatments. This study performed a cost-analysis of ultrafiltration (UF) vs diuretic therapy (DIUR-T) for patients with HF from the hospital perspective.

Methods: The model used clinical data from the literature and hospital data from the Healthcare Cost and Utilization Project to follow a decision-analytic framework reflecting treatment decisions, probabilistic outcomes, and associated costs for treating patients with HF and hypervolemia with veno-venous UF or intravenous DIUR-T. A 90-day timeframe was considered to account for hospital readmissions beyond 30?days. Sensitivity and scenario analyses were performed to gauge the robustness of the results.

Results: Although initial hospitalization costs were higher, fluid removal by UF reduced hospital readmission days, leading to cost savings of $3,975 (14.4%) at the 90-day follow-up (UF costs, $23,633; DIUR-T costs, $27,608).

Conclusions: UF is a viable alternative to DIUR-T when treating fluid overload in HF patients because it reduces hospital readmission rates and durations, which substantially lowers costs over a 90-day period compared to DIUR-T.     

The effect of major adverse renal cardiovascular event (MARCE) incidence,procedure volume,and unit cost on the hospital savings resulting from contrast media use in inpatient angioplasty

Objective: To determine the net economic impact of switching from low-osmolar contrast media (LOCM) to iso-osmolar contrast media (IOCM; iodixanol) in patients undergoing inpatient coronary or peripheral angioplasty in the United States (US).

Methods: A budget impact model (BIM) was developed from a hospital perspective. Nationally representative procedural and contrast media prevalence rates, along with MARCE (major adverse renal cardiovascular event) incidence and episode-related cost data were derived from Premier Hospital Data (October 2014 to September 2015). A previously estimated relative risk reduction in MARCE associated with IOCM usage (9.3%) was applied. The higher cost of IOCM was included when calculating the net impact estimates at the aggregate, hospital type, and per hospital levels. One-way (±25%) and probabilistic sensitivity analyses identified the model’s most important inputs.

Results: Based on weighted analysis, 513,882?US inpatient angioplasties and 35,610 MARCE cases were estimated annually. Switching to an “IOCM only” strategy from a “LOCM only” strategy increases contrast media cost, but prevents 2,900 MARCE events. The annual budget impact was an estimated saving of $30.71 million, aggregated across all US hospitals, $6,316 per hospital, or $60 per procedure. Net savings were maintained across all univariate sensitivity analyses. While MARCE/event-free cost differential was the most important factor driving total net savings for hospitals in the Northeast and West, procedural volume was important in the Midwest and rural locations.

Conclusions: Switching to an “IOCM only” strategy from a “LOCM only” approach yields substantial net global savings to hospitals, both at the national level and within hospital sub-groups. Hospital administrators should maintain awareness of the factors that are likely to be more influential for their hospital and recognize that purchasing on the basis of lower contrast media cost may result in higher overall costs for patients undergoing inpatient angioplasty.     

Estimated medical cost reductions associated with use of novel oral anticoagulants vs warfarin in a real-world non-valvular atrial fibrillation patient population

Objective:

Results of randomized clinical trials (RCT) demonstrate that novel oral anticoagulants (NOAC) are effective therapies for reducing the risk of stroke in non-valvular atrial fibrillation (NVAF). Prior medical cost avoidance studies have used warfarin event rates from RCTs, which may differ from patients receiving treatment in a real-world (RW) setting, where the quality of care may not be the same as in a RCT. The purpose of this study was to estimate the change in medical costs related to stroke and major bleeding for each NOAC (apixaban, dabigatran, and rivoraxaban) relative to warfarin in a RW NVAF population.

Methods:

Patients (n?=?23,525) with a diagnosis of NVAF during 2007–2010 were selected from a Medco population of US health plans. Stroke and major bleeding excluding intracranial hemorrhage (MBEIH) events were identified using diagnosis codes on medical claims. RW reference event rates were calculated during periods of warfarin exposure. RW event rates for NOACs were estimated by multiplying the corresponding relative risk (RR) from the RCTs by each reference rate. Absolute risk reductions (ARR) or number of events avoided per patient year were then estimated. Changes in medical costs associated with each NOAC were calculated by applying the ARR to the 1-year cost for each event. Costs for stroke and MBEIH were obtained from the literature. Drug and international normalized ratio monitoring costs were not considered in this analysis.

Results:

Compared to RW warfarin, use of apixaban and dabigatran resulted in total (stroke plus MBEIH) medical cost reductions of $1245 and $555, respectively, during a patient year. Rivaroxaban resulted in a medical cost increase of $144.

Conclusions:

If relative risk reductions demonstrated in RCTs persist in a RW setting, apixaban would confer the greatest medical cost savings vs warfarin, resulting from significantly lower rates of both stroke and MBEIH.     

The burden of preserved ejection fraction heart failure in a real-world Swedish patient population

Objectives:

To evaluate resource use and associated costs in patients with a diagnosis of heart failure with preserved ejection fraction (HF-PEF) in Sweden.

Methods:

This retrospective study identified real-world patients with an ICD-10 diagnosis code for heart failure (I50) for the period between July 1, 2005 and December 31, 2006 from electronic medical records of primary care centers in Uppsala County Council, and in the Swedish patient registry data. Patients were categorized as having HF-PEF (left ventricle ejection fraction [LVEF] > 50%) during the index period. The study assessed medication utilization, outpatient visits, hospitalizations, and associated healthcare costs, as well as the incidence rates and time to all-cause and heart failure mortality following the index period.

Results:

The study included 137 HF-PEF patients with a mean age of 77.1 (SD?=?9.1) years. Over 50% of HF-PEF patients were female and hypertensive. Nearly all patients received ≥1 medication post-index. Patients had an average of 1.5 heart failure related hospitalizations per follow-up year. The average annual per patient cost for the management of a HF-PEF patient was found in Sweden to be Swedish Krona (SEK) 108,246 (EURO [EUR] 11,344). Hospitalizations contributed to more than 80% of the total cost. All-cause mortality over the 18-month study period was 25.5%, and more than 50% of these deaths occurred within 1 year of index.

Limitations:

Due to the limitations of registry data, it is not possible to confirm the HF diagnosis, and therefore the accuracy of registry records must be assumed. Other factors such as short follow-up time, the study-mandated LVEF assessment, and a lack of drug duration data may also have an impact on the study results.

Conclusions:

All-cause mortality was high in the HF-PEF population, with more than half of patients dying within 1 year of study follow-up. Study results also indicate that 60% of HF-PEF patients have ≥1 hospitalization during follow-up. Hospitalizations, especially heart failure related admissions, represent a substantial proportion of the total healthcare burden of patients with HF-PEF in Sweden.     

Cost-effectiveness analysis of ferric carboxymaltose in iron-deficient patients with chronic heart failure in Sweden

Abstract

Objective:

Iron deficiency is a common but treatable comorbidity in chronic heart failure (CHF) that is associated with impaired health-related quality-of-life (HRQoL). This study evaluates the cost-effectiveness of the intravenous iron preparation ferric carboxymaltose (FCM) for the treatment of iron deficiency in CHF from a Swedish healthcare perspective.     

L-carnitine in the management of patients after acute myocardial infarction: a cost effectiveness analysis in Italy

Summary

The prevalence of acute myocardial infarction (AMI) is estimated at 500,000 individuals in the Italian population; the annual incidence can be crudely estimated at 100,000 events. This represents a major healthcare problem and generates questions about the rational allocation of public resources devoted to healthcare, since in Italy there is a National Health Service. We focused on modelling the possible economic consequences of adding L-carnitine administration to the standard care of AMI patients in Italy, by extrapolating the results obtained in the SAVE trial and matching entry criteria from the CEDIM and SAVE studies. The cost-effectiveness ratios were explored using different assumptions of the effectiveness and cost of the intervention under analysis. In our base case, administering L-carnitine had an Incremental Cost/Effectiveness Ratio of 28.2 and 22.2 million Lira per life year saved (LYS), respectively, depending on whether discounted or non-discounted benefits were used in this model. The results were sensitive to both the cost and effectiveness of L-carnitine.     

Real-world comparison of hospitalization costs for heart failure in type 2 diabetes mellitus patients with established cardiovascular disease treated with canagliflozin versus other antihyperglycemic agents

Abstract

Aims: This real-world study compared hospitalization for heart failure (HHF) costs and all-cause healthcare costs in patients with type 2 diabetes mellitus (T2DM) and established cardiovascular disease treated with the sodium glucose co-transporter 2 inhibitor (SGLT2i) canagliflozin and non-SGLT2i antihyperglycemic agents (AHAs).

Materials and methods: Propensity score-matched cohorts from a retrospective observational study (OBSERVE-4D) using the Truven MarketScan Commercial Claims and Encounters and Optum Clinformatics databases were analyzed. HHF and all-cause healthcare costs per-patient-per-month (PPPM) were compared for patients initiated on canagliflozin and non-SGLT2i AHAs in the on-treatment analysis.

Results: Baseline characteristics were well balanced between matched cohorts that included new users of canagliflozin or non-SGLT2i AHAs in the Truven (13,954 and 45,101, respectively) and Optum (11,490 and 53,360, respectively) databases. The mean (95% CI) PPPM cost of HHF was lower for canagliflozin than for non-SGLT2i AHAs in analyses of both the Truven ($21.31 [$21.25, $21.37]) and Optum ($30.43 [$30.41, $30.45]) databases. The mean (95% CI) PPPM all-cause healthcare cost was also lower for canagliflozin than for non-SGLT2i AHAs in analyses of both the Truven ($321 [$280, $361]) and Optum ($449 [$402, $495]) databases.

Limitations: This study is subject to the limitations inherent to observational research including potential for coding errors and biases and unobserved confounding. Because all patients were in commercially administered health plans, these findings cannot be easily generalized to uninsured or Medicaid populations. Patient costs were evaluated up to and including their first HHF event. Post-discharge costs such as the costs of subsequent rehospitalizations were not included in this analysis.

Conclusions: For patients with T2DM and established cardiovascular disease in this real-world study, treatment with canagliflozin was associated with lower HHF costs and all-cause healthcare costs compared with treatment with non-SGLT2i AHAs.     

US budget impact of increased payer adoption of the Flexitouch advanced pneumatic compression device in lymphedema patients with advanced chronic venous insufficiency and multiple infections

Aims: To assess the budget impact to a US commercial health plan of providing access to the Flexitouch (FLX) advanced pneumatic compression device (Tactile Medical) to lymphedema (LE) patients with either comorbid chronic venous insufficiency (CVI) or frequent infections.

Methods: Budget impact was calculated over 2 years for a hypothetical US payer with 10-million commercial members. Model inputs were derived from published sources and from a case-matched analysis of Blue Health Intelligence (BHI) claims data for the years 2012–2016. To calculate the budget impact, the Status Quo budget (i.e. total cost for LE and sequelae-related medical treatment) was compared to the budget under each of three Alternate Payer Policy scenarios which assumed that a sub-set of patients was redistributed from their initial treatment groups to a group that received FLX. Model outputs included cumulative payer costs, net budget impact, and breakeven point. Sensitivity analyses were performed to assess the impact of model inputs on results.

Results: Increasing access to FLX yielded a favorable budget impact in every scenario. For LE patients with comorbid CVI, the three alternate scenarios resulted in cumulative 2-year budget impacts of –$52,841, –$173,317, and –$375,601, respectively. For LE patients with comorbid frequent infections, the three alternate scenarios resulted in cumulative 2-year budget impacts of –$192,729, –$259,339, and –$613,179, respectively.

Limitations: Use of claims data assumes accurate coding and does not allow one to control for disease severity or treatment adherence. Also, the distribution of patients between treatment arms was determined using claims data from a specific payer organization, and could differ for health plans with different coverage policies.

Conclusions: While previous studies have illustrated cost savings with adoption of FLX, US commercial health plans may also achieve tangible cost savings by expanding access to FLX for LE patients with comorbid CVI and multiple infections.