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.     

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.     

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.     

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.