Benefits of dapagliflozin in chronic kidney disease for US commercial payers: A cost-offset analysis.

BACKGROUND: One in 7 adults have chronic kidney disease (CKD), which is associated with high morbidity and mortality and substantial health care costs, especially in more advanced disease. Our data from a US commercial payer show rising per-member-per-year costs for renal and cardiac complications associated with CKD. OBJECTIVE: To predict the clinical and economic impact of treatment with or without dapagliflozin from the perspective of a US commercial payer using a cost-offset model (COM). METHODS: The COM used real-world cost and member count data from a US employer-sponsored commercial payer and results of the double-blind, randomized, phase 3 Dapagliflozin and Prevention of Adverse Outcomes in CKD clinical trial (NCT03036150) to predict the incidence of clinical events, including a greater than or equal to 50% decline in estimated glomerular filtration rate (eGFR), end-stage kidney disease, and hospitalization for heart failure, and their associated costs over a 3-year period. The COM compared a hypothetical scenario of the experience with or without dapagliflozin in members with CKD stages 2-4, aged younger than 65 years. RESULTS: In the simulated populations of 130 members, the COM projected 9 events of a greater than or equal to 50% decline in estimated glomerular filtration rate for the experience with dapagliflozin vs 15 events for the experience without dapagliflozin (6 fewer events; number needed to treat [NNT] = 20, amounting to estimated cumulative cost offsets of $0.57 million [M] over a 3-year period). The COM projected similar results for end-stage kidney disease (8 events with dapagliflozin vs 14 events without dapagliflozin; NNT = 24, amounting to $1.92 M in cumulative cost offsets) and for hospitalization for heart failure (13 events with dapagliflozin vs 33 events without dapagliflozin; NNT = 7, amounting to $0.79 M in cumulative cost offsets). These projections translated to total mean, cumulative cost offsets of $3.89 M for all clinical events evaluated over the 3-year period (36.6% reduction with dapagliflozin vs without dapagliflozin), and net mean, cumulative cost offsets of $2.58 M over the 3-year period (24.2% reduction with dapagliflozin vs without dapagliflozin) after factoring in a discounted wholesale acquisition cost for dapagliflozin expenditure ($1.31 M over 3 years). Thus, the net mean, cumulative cost offsets were $19,843 per member over 3 years, representing a 197% return on investment for dapagliflozin expenditure. CONCLUSIONS: Results of our COM suggest that dapagliflozin can reduce clinical events and their associated costs over a 3-year period when compared with a scenario without dapagliflozin. Cost offsets increased with each year, indicating that US commercial payers can substantially reduce costs associated with CKD morbidity and mortality.

How adoption of new pharmaceuticals can impact US health system reimbursement under alternative payment models: An economic model measuring the impact of sotagliflozin among patients with heart failure and diabetes.

BACKGROUND: Heart failure (HF) is among the leading causes of death in the United States. Further, patients hospitalized because of HF with comorbid diabetes mellitus (DM) are at a significantly increased risk of death and rehospitalization. Results from the SOLOIST-WHF trial show that sotagliflozin lowered rates of readmission among hospitalized patients with HF and comorbid DM. However, it is unclear what the economic impact of the use of sotagliflozin would be on hospitals and health systems, particularly in an age where provider reimbursement is increasingly tied to value. OBJECTIVE: To quantify the 1-year financial impact on US provider health systems of adopting sotagliflozin relative to standard of care (SoC) across different alternative payment models. METHODS: This study created a 3-part decision tree model to quantify the financial impact of using sotagliflozin to treat patients hospitalized with HF in a US hospital setting. The model first estimated the clinical and economic outcomes of health systems with current SoC (no sotagliflozin) to treat US patients hospitalized for HF with comorbid DM. Then, using the results from the SOLOIST trial, the changes in clinical and economic outcomes with sotagliflozin adoption were modeled. Finally, the differences in health care utilization between sotagliflozin and SoC arms were translated to differences in health system reimbursement in the context of 3 common alternative payment models (APMs) in addition to the baseline fee-for-service (FFS) model: FFS with the Hospital Readmissions Reduction Program, the Bundled Payments for Care Improvement-Advanced program, and Accountable Care Organizations. RESULTS: A typical community hospital would have 83.4 patients per year on average with an index HF hospitalization with comorbid DM. The model predicted that sotagliflozin would reduce the probability of hospitalization, emergency department visits, and deaths by 29.3%, 38.5%, and 17.8%, respectively, compared with SoC. For hospitals not participating in APM programs, sotagliflozin resulted in a net loss of $92.94 per person ($7,754 per health system). Conversely, when accounting for provider health system participation in APMs, sotagliflozin adoption increased financial returns by $4,720 per person ($305,604 per health system) under the Hospital Readmissions Reduction Program, $1,200 per person ($100,106 per health system) for the Bundled Payments for Care Improvement-Advanced program, and $1,078 per person ($31,029 per health system) for Accountable Care Organizations. Based on the national average composition of APM reimbursement, sotagliflozin adoption resulted in a $1,576 increase in margin per patient with HF ($105,454 per health system). CONCLUSIONS: Although sotagliflozin adoption reduced health system revenue in an FFS payment model, it led to a net positive financial impact after accounting for APM bonus payments.

Cost Offset of Dapagliflozin in the US Medicare Population with Cardio-Kidney Metabolic Syndrome.

INTRODUCTION: Cardiovascular-kidney-metabolic (CKM) syndrome is highly prevalent in the US Medicare population and is projected to increase further. Sodium-glucose co-transporter 2 inhibitors have indications in chronic kidney disease (CKD), heart failure (HF), and type 2 diabetes (T2D), providing protective efficacy across conditions within CKM syndrome. The objective of this study was to develop a model to extrapolate key outcomes observed in pivotal clinical trials to the US Medicare population, and to assess the potential direct cost offsets associated with dapagliflozin therapy. METHODS: All US 2022 Medicare beneficiaries (≥ 65 years of age) eligible to receive dapagliflozin were estimated according to drug label indication and Medicare enrollment and claims data. Incidence of key outcomes from the dapagliflozin clinical program were modelled over a 4-year time horizon based on patient-level data with CKD, HF, and T2D. Published cost data of relevant clinical outcomes were used to calculate direct medical care cost-offset associated with treatment with dapagliflozin. RESULTS: In a population of 13.1 million patients with CKM syndrome, treatment with dapagliflozin in addition to historical standard of care (hSoC) versus hSoC alone led to fewer incidents of HF-related events (hospitalization for HF, 613,545; urgent HF visit, 98,896), renal events (kidney failure, 285,041; ≥ 50% sustained decline in kidney function, 375,137), and 450,355 fewer deaths (of which 225,346 and 13,206 incidences of cardiovascular and renal death were avoided). In total this led to medical care cost offsets of $99.3 billion versus treatment with hSoC only (dapagliflozin plus hSoC, $310.3 billion; hSoC, $211.0 billion). CONCLUSION: By extrapolating data from trials across multiple indications within CKM syndrome, this broader perspective shows that considerable medical care cost offsets may result through attenuated incidence of clinical events in CKD, T2D, and HF populations if treated with dapagliflozin in addition to hSoC over a 4-year time horizon. Graphical abstract available for this article.

Cost-effectiveness of add-on empagliflozin versus standard of care in management of CKD in Malaysia, Thailand and Vietnam - findings from a modelling study assessing an EMPA-KIDNEY eligible population, using CKD progression model.

BACKGROUND AND OBJECTIVES: Nearly one in ten individuals in South-East Asia are estimated to be affected by chronic kidney disease (CKD). The burden of end-stage kidney disease is significant and can be heavy on the healthcare system. The recent EMPA-KIDNEY trial demonstrated a significant reduction in the risk of kidney disease progression or cardiovascular death in patients with CKD with a broad range of kidney function using add-on empagliflozin versus standard of care (SoC) alone. The objective of this study was to estimate the economic benefit of empagliflozin for patients with CKD in Malaysia, Thailand and Vietnam. METHODS: An individual patient level simulation model with an annual cycle that estimates the progression of kidney function and associated risk-factors was employed. Local costs and mortality rates were estimated from a wide range of published literature. A healthcare perspective was used over a 50-year time horizon. RESULTS: The use of add-on empagliflozin versus SoC alone was found to be cost-saving in Malaysia and Thailand and cost-effective (ICER: 77,838,407 Vietnam Dong/QALY vs. a willingness to pay threshold of 96,890,026/QALY) in Vietnam. The bulk of the costs avoided over a lifetime is derived from the prevention or delay of dialysis initiation or kidney transplant - the cost offsets were nearly twice the additional treatment cost. The results were similar in patients with and without diabetes and across broad range of albuminuria. CONCLUSIONS: The use of add-on empagliflozin in a broad population of patients with CKD is expected to be cost-saving in Malaysia and Thailand and cost-effective in Vietnam and will help alleviate the increasing burden of CKD in the region.

Cause-Specific Health Care Costs Following Hospitalization for Heart Failure and Cost Offset With SGLT2i Therapy.

BACKGROUND: Little is known regarding differences in cause-specific costs between heart failure (HF) with ejection fraction (EF) ≤40% vs >40%, and potential cost implications of sodium glucose co-transporter 2 inhibitor (SGLT2i) therapy. OBJECTIVES: This study sought to compare cause-specific health care costs following hospitalization for HF with EF ≤40% vs >40% and estimate the cost offset with implementation of SGLT2i therapy. METHODS: This study examined Medicare beneficiaries hospitalized for HF in the Get With The Guidelines-Heart Failure registry from 2016 to 2020. Mean per-patient total (excluding drug costs) and cause-specific costs from discharge through 1-year follow-up were calculated and compared between EF ≤40% vs >40%. Next, risk reductions on total all-cause and HF hospitalizations were estimated in a trial-level meta-analysis of 5 pivotal trials of SGLT2is in HF. Finally, these relative treatment effects were applied to Medicare beneficiaries eligible for SGLT2i therapy to estimate the projected cost offset with implementation of SGLT2i, excluding drug costs. RESULTS: Among 146,003 patients, 50,598 (34.7%) had EF ≤40% and 95,405 (65.3%) had EF >40%. Mean total cost through 1 year was $40,557. Total costs were similar between EF groups overall but were higher for EF ≤40% among patients surviving the 1-year follow-up period. Patients with EF >40% had higher costs caused by non-HF and noncardiovascular hospitalizations, and skilled nursing facilities (all P < 0.001). Trial-level meta-analysis of the 5 SGLT2i clinical trials estimated 11% (rate ratio: 0.89; 95% CI: 0.84-0.93; P < 0.001) and 29% (rate ratio: 0.71; 95% CI: 0.66-0.76; P < 0.001) relative reductions in rates of total all-cause and HF hospitalizations, respectively, regardless of EF. Reductions in all-cause and HF hospitalizations were projected to reduce annual costs of readmission by $2,451 to $2,668 per patient with EF ≤40% and $1,439 to $2,410 per patient with EF >40%. CONCLUSIONS: In this large cohort of older U.S. adults hospitalized for HF, cause-specific costs of care differed among patients with EF ≤40% vs >40%. SGLT2i significantly reduced the rate of HF and all-cause hospitalizations irrespective of EF in clinical trials, and implementation of SGLT2i therapy in clinical practice is projected to reduce costs by $1,439 to $2,668 per patient over the 1 year post-discharge, excluding drug costs.

The national financial burden of guideline directed medical therapy for heart failure patients from 2013 to 2021.

BACKGROUND: Guideline Directed Medical Therapy (GDMT) has been revolutionary in improving outcomes of heart failure patients. However, with the addition of more medication classes, the annual cost of these medications on the US healthcare system needs further evaluation. OBJECTIVES: We aim to evaluate the trend of annual cost of GDMT from 2013 to 2021 using the Medicare-part D Database. METHODS: Using Medicare Part D database (2013-2021), we determined the number of beneficiaries receiving these drugs, the total number of 30-day fills for each medication, and the total annual spending on these medications. Linear regression was used to analyze data using Python Programming Language. P value of less than 0.05 was considered to be statistically significant. RESULTS: The estimated annual Medicare- part D spending on empagliflozin had a 50 % increase in cost between 2020 and 2021, which could be attributed to its FDA approval for heart failure with reduced ejection fraction. Empagliflozin cost Medicare 3.73 billion USD in 2021 alone. In addition, sacubitril-valsartan had a strong trajectory since its introduction to the market in 2015. Since its approval in July 2015, it cost Medicare 4.51 billion USD. The Mineralocorticoid Receptor Antagonist class was the least costly class of GDMT. CONCLUSION: The rise in the cost of GDMT is not proportionate amongst the different classes of GDMT. Newer classes of medications cast a significant cost on Medicare in recent years.

Cost-effectiveness of empagliflozin as add-on to standard of care for chronic kidney disease management in the United Kingdom.

OBJECTIVE: The sodium-glucose co-transporter-2 inhibitor empagliflozin was approved for treatment of adults with chronic kidney disease (CKD) on the basis of its demonstrated ability to slow CKD progression and reduce the risk of cardiovascular death. This analysis was performed to assess the cost-effectiveness of empagliflozin plus standard of care (SoC) vs SoC alone in the treatment of CKD in the UK. METHODS: A comprehensive, patient-level CKD progression model that simulates the evolution of risk factors for disease progression based on CKD-specific equations and clinical data was used to project a broad range of CKD-related complications. Patient baseline characteristics, distribution across Kidney Disease Improving Global Outcomes (KDIGO) health states, and changes in estimated glomerular filtration rate (eGFR), urine albumin-creatinine ratio (uACR), and other parameters while on treatment were derived from the EMPA-KIDNEY trial. UK cost and utilities/disutilities were sourced from the literature. Univariate and probabilistic sensitivity analyses were conducted. Annual discounting of 3.5% was applied on costs and outcomes. RESULTS: Over a 50-year horizon, SoC resulted in per-patient costs, life years, and QALYs of £95,930, 8.55, and 6.28, respectively. Empagliflozin plus SoC resulted in an incremental gain in life years (+1.04) and QALYs (+0.84), while decreasing per-patient costs by £6,019. Empagliflozin was more effective and less costly (dominant) with a net monetary benefit of £22,849 at the willingness-to-pay threshold of £20,000. Although treatment cost was higher for empagliflozin, this was more than offset by savings in kidney replacement therapy. Empagliflozin remained highly cost-effective in patients with and without diabetes, and across scenario and sensitivity analyses. LIMITATIONS: This analysis is limited by reliance on short-term clinical trial data and by uncertainties in modelling CKD progression. CONCLUSIONS: Empagliflozin as an add-on to SoC for treatment of adults with CKD represents cost-effective use of UK National Health Service (NHS) resources.

Cost-effectiveness of sotagliflozin for the treatment of patients with diabetes and recent worsening heart failure.

Aim: To assesses the cost-effectiveness of sotagliflozin for the treatment of patients hospitalized with heart failure and comorbid diabetes. Materials & methods: A de novo cost-effectiveness model with a Markov structure was created for patients hospitalized for heart failure with comorbid diabetes. Outcomes of interest included hospital readmissions, emergency department visits and all-cause mortality measured over a 30-year time horizon. Baseline event frequencies were derived from published real-world data studies; sotagliflozin's efficacy was estimated from SOLOIST-WHF. Health benefits were calculated quality-adjusted life years (QALYs). Costs included pharmaceutical costs, rehospitalization, emergency room visits and adverse events. Economic value was measured using the incremental cost-effectiveness ratio (ICER). Results: Sotagliflozin use decreased annualized rehospitalization rates by 34.5% (0.228 vs 0.348, difference: -0.120), annualized emergency department visits by 40.0% (0.091 vs 0.153, difference: -0.061) and annualized mortality by 18.0% (0.298 vs 0.363, difference: -0.065) relative to standard of care, resulting in a net gain in QAYs of 0.425 for sotagliflozin versus standard of care. Incremental costs using sotagliflozin increased by $19,374 over a 30-year time horizon of the patient, driven largely by increased pharmaceutical cost. Estimated ICER for sotagliflozin relative to standard of care was $45,596 per QALY. Conclusion: Sotagliflozin is a cost-effective addition to standard of care for patients hospitalized with heart failure and comorbid diabetes.

Comparing the effectiveness and cost-effectiveness of sulfonylureas and newer diabetes drugs as second-line therapy for patients with type 2 diabetes.

INTRODUCTION: We aimed to compare the effectiveness and cost-effectiveness profiles of glucagon-like peptide-1 receptor agonist (GLP-1-RA), sodium-glucose cotransporter 2 inhibitor (SGLT2i), and dipeptidyl peptidase-4 inhibitor (DPP-4i) compared with sulfonylureas and glinides (SU). RESEARCH DESIGN AND METHODS: Population-based retrospective cohort study based on linked regional healthcare utilization databases. The cohort included all residents in Lombardy aged ≥40 years, treated with metformin in 2014, who started a second-line treatment between 2015 and 2018 with SU, GLP-1-RA, SGLT2i, or DPP-4i. For each cohort member who started SU, one patient who began other second-line treatments was randomly selected and matched for sex, age, Multisource Comorbidity Score, and previous duration of metformin treatment. Cohort members were followed up until December 31, 2022. The association between second-line treatment and clinical outcomes was assessed using Cox proportional hazards models. The incremental cost-effectiveness ratios (ICERs) were calculated and compared between newer diabetes drugs and SU. RESULTS: Overall, 22 867 patients with diabetes were included in the cohort, among which 10 577, 8125, 2893 and 1272 started a second-line treatment with SU, DPP-4i, SGLT2i and GLP-1-RA, respectively. Among these, 1208 patients for each group were included in the matched cohort. As compared with SU, those treated with DPP-4i, SGLT2i and GLP-1-RA were associated to a risk reduction for hospitalization for major adverse cardiovascular events (MACE) of 22% (95% CI 3% to 37%), 29% (95% CI 12% to 44%) and 41% (95% CI 26% to 53%), respectively. The ICER values indicated an average gain of €96.2 and €75.7 each month free from MACE for patients on DPP-4i and SGLT2i, respectively. CONCLUSIONS: Newer diabetes drugs are more effective and cost-effective second-line options for the treatment of type 2 diabetes than SUs.

Cost-Effectiveness of Medical Therapy for Heart Failure With Mildly Reduced and Preserved Ejection Fraction.

BACKGROUND: Three medications are now guideline-recommended treatments for heart failure with mildly reduced or preserved ejection fraction (HFmrEF/HFpEF), however, the cost-effectiveness of these agents in combination has yet to be established. OBJECTIVES: The purpose of this study was to determine the cost-effectiveness of mineralocorticoid receptor antagonists (MRA), angiotensin receptor-neprilysin inhibitors (ARNIs), and sodium glucose co-transporter 2 inhibitors (SGLT2is) in individuals with HFmrEF/HFpEF. METHODS: Using a 3-state Markov model, we performed a cost-effectiveness study using simulated cohorts of 1,000 patients with HFmrEF and HFpEF. Treatment with 1-, 2-, and 3-drug combinations was modeled. Based on a United States health care sector perspective, outcome data was used to calculate incremental cost-effectiveness ratios (ICERs) in 2023 United States dollars based on a 30-year time horizon. RESULTS: Treatment with MRA, MRA+SGLT2i, and MRA+SGLT2i+ARNI therapy resulted in an increase in life years of 1.04, 1.58, and 1.80 in the HFmrEF subgroup, respectively, and 0.99, 1.54, and 1.77 in the HFpEF subgroup, respectively, compared with placebo. At a yearly cost of $18, MRA therapy resulted in ICERs of $10,000 per quality-adjusted life year (QALY) in both subgroups. The ICER for the addition of SGLT2i therapy ($4,962 per year) was $113,000 per QALY in the HFmrEF subgroup and $141,000 in the HFpEF subgroup. The addition of ARNI therapy ($5,504 per year) resulted in ICERs >$250,000 per QALY in both subgroups. If SGLT2i and ARNI were available at generic pricing the ICERs become <$10,000 per QALY in both EF subgroups. Outcomes were highly sensitive to assumed benefit in cardiovascular death. CONCLUSIONS: For patients with heart failure, MRA was of high value, SGLT2i was of intermediate value, and ARNI was of low value in both HFmrEF and HFpEF subgroups. For patients with HFmrEF/HFpEF increased use of MRA and SGLT2i therapies should be encouraged and be accompanied with efforts to lower the cost of SGLT2i and ARNI therapies.

Health and economic impact of dapagliflozin for type 2 diabetes patients who had or were at risk for atherosclerotic cardiovascular disease in the Italian general practitioners setting: a budget impact analysis.

AIM: In 2022, in Italy, general practitioners (GPs) have been allowed to prescribe SGLT2i in Type 2 Diabetes (T2D) under National Health Service (NHS) reimbursement. In the pivotal clinical trial named DECLARE-TIMI 58, dapagliflozin reduced the risk of hospitalization for heart failure, CV death and kidney disease progression compared to placebo in a population of T2D patients. This study evaluated the health and economic impact of dapagliflozin for T2D patients who had or were at risk for atherosclerotic cardiovascular disease in the Italian GPs setting. METHODS: A budget impact model was developed to assess the health and economic impact of introducing dapagliflozin in GPs setting. The analysis was conducted by adopting the Italian NHS perspective and a 3-year time horizon. The model estimated and compared the health outcomes and direct medical costs associated with a scenario with dapagliflozin and other antidiabetic therapies available for GPs prescription (scenario B) and a scenario where only other antidiabetic therapies are available (scenario A). Rates of occurrence of cardiovascular and renal complications as well as adverse events were captured from DECLARE-TIMI 58 trial and the literature, while cost data were retrieved from the Italian tariff and the literature. One-way sensitivity analyses were conducted to test the impact of model parameters on the budget impact. RESULTS: The model estimated around 442.000 patients eligible for the treatment with dapagliflozin in the GPs setting for each simulated year. The scenario B compared to scenario A was associated with a reduction in the occurrence of cardiovascular and renal complication (-1.83%) over the 3 years simulated. Furthermore, the scenario A allowed for an overall cost saving of 102,692,305€: 14,521,464€ in the first year, 33,007,064€ in the second and 55,163,777€ in the third. The cost of cost of drug acquisition, the probability of cardiovascular events and the percentage of patients potentially eligible to the treatment were the factor with largest impact on the results. CONCLUSIONS: The use of dapagliflozin in GPs setting reduce the number of CVD events, kidney disease progression and healthcare costs in Italy. These data should be considered to optimize the value produced for the T2D patients who had or were at risk for atherosclerotic cardiovascular disease.

Cost-Effectiveness of Newer Pharmacologic Treatments in Adults With Type 2 Diabetes: A Systematic Review of Cost-Effectiveness Studies for the American College of Physicians.

BACKGROUND: In the United States, costs of antidiabetes medications exceed $327 billion. PURPOSE: To systematically review cost-effectiveness analyses (CEAs) of newer antidiabetes medications for type 2 diabetes. DATA SOURCES: Bibliographic databases from 1 January 2010 through 13 July 2023, limited to English. STUDY SELECTION: Nonindustry-funded CEAs, done from a U.S. perspective that estimated cost per quality-adjusted life-year (QALY) gained for newer antidiabetic medications. Two reviewers screened the literature; disagreements were resolved with a third reviewer. DATA EXTRACTION: Cost-effectiveness analyses were reviewed for treatment comparisons, model inputs, and outcomes. Risk of bias (RoB) of the CEAs was assessed using Drummond criteria and certainty of evidence (CoE) was assessed using GRADE (Grading of Recommendations Assessment, Development, and Evaluations). Certainty of evidence was determined using cost per QALY thresholds predetermined by the American College of Physicians Clinical Guidelines Committee; low (>$150 000), intermediate ($50 to $150 000), or high (<$50 000) value per QALY compared with the alternative. DATA SYNTHESIS: Nine CEAs were eligible (2 low, 1 high, and 6 some concerns RoB), evaluating glucagon-like peptide-1 agonists (GLP1a), dipeptidyl peptidase-4 inhibitors (DPP4i), sodium-glucose cotransporter-2 inhibitors (SGLT2i), glucose-dependent insulinotropic peptide agonist (GIP/GLP1a), and insulin. Comparators were metformin, sulfonylureas, neutral protamine Hagedorn (NPH) insulin, and others. Compared with metformin, GLP1a and SGLT2i are low value as first-line therapy (high CoE) but may be of intermediate value when added to metformin or background therapy compared with adding nothing (low CoE). Insulin analogues may be similarly effective but more expensive than NPH insulin (low CoE). The GIP/GLP1a value is uncertain (insufficient CoE). LIMITATIONS: Cost-effectiveness analyses varied in methodological approach, assumptions, and drug comparisons. Risk of bias and GRADE method for CEAs are not well established. CONCLUSION: Glucagon-like peptide-1 agonists and SGLT2i are of low value as first-line therapy but may be of intermediate value when added to metformin or other background therapy compared with adding nothing. Other drugs and comparisons are of low or uncertain value. Results are sensitive to drug effectiveness and cost assumptions. PRIMARY FUNDING SOURCE: American College of Physicians. (PROSPERO: CRD42022382315).

Cost-effectiveness of dapagliflozin for patients with heart failure across the spectrum of ejection fraction: A pooled analysis of DAPA-HF and DELIVER data.

AIM: To assess the cost-effectiveness of dapagliflozin in addition to usual care, compared with usual care alone, in a large population of patients with heart failure (HF), spanning the full range of left ventricular ejection fraction (LVEF). METHODS AND RESULTS: Patient-level data were pooled from HF trials (DAPA-HF, DELIVER) to generate a population including HF with reduced, mildly reduced and preserved LVEF, to increase statistical power and enable exploration of interactions among LVEF, renal function and N-terminal pro-B-type natriuretic peptide levels, as they are relevant determinants of health status in this population. Survival and HF recurrent event risk equations were derived and applied to a lifetime horizon Markov model with health states defined by Kansas City Cardiomyopathy Questionnaire total symptom score quartiles; costs and utilities were in the UK setting. The base case incremental cost-effectiveness ratio (ICER) was £6470 per quality-adjusted life year (QALY) gained, well below the UK willingness-to-pay (WTP) threshold of £20 000/QALY gained. In interaction sensitivity analyses, the highest ICER was observed for elderly patients with preserved LVEF (£16 624/QALY gained), and ranged to a region of dominance (increased QALYs, decreased costs) for patients with poorer renal function and reduced/mildly reduced LVEF. Results across the patient characteristic interaction plane were mostly between £5000 and £10 000/QALY gained. CONCLUSIONS: Dapagliflozin plus usual care, versus usual care alone, yielded results well below the WTP threshold for the UK across a heterogeneous population of patients with HF including the full spectrum of LVEF, and is likely a cost-effective intervention.

Cost-Effectiveness of New Quadruple Therapy Compared With Standard Treatment for Patients With Heart Failure in China.

ABSTRACT: This study aimed to compare the cost-effectiveness of the new quadruple therapy regimen of adding sodium-glucose-linked transporter 2 (SGLT2) inhibitors, with standard treatment for patients with heart failure (HF) in China. From the payer's perspective, the dates of cardiovascular event recurrences were extracted from a meta-analysis including 6 trials, combined with the treatment cost for patients with HF in China to construct a Markov model. The outcomes included per capita medical costs and incremental cost-effectiveness ratio, using quality-adjusted life years (QALYs) data. Single-factor, probability sensitivity analysis, and scenario analysis were used to explore the potential uncertainties of the model. The per capita costs of the new quadruple therapy regimen and standard treatment were $87441.26 and $87087.54, respectively. The new regimen was associated with a mean of 21.44 QALYs gained, compared with 18.60 QALYs gained with the standard treatment. The incremental cost-effectiveness ratio was $124.03 per QALY gained. The sensitivity analysis revealed that changes in the parameters within the set range did not affect the model results. In China, compared with standard treatment, the new quadruple therapy regimen with SGLT2 inhibitors reduce the frequency of cardiovascular events among patients with HF, and it has economic advantages.

The health and budget impact of sodium-glucose co-transporter-2 inhibitors (SGLT2is) in The Netherlands.

OBJECTIVES: Type-2 Diabetes mellitus (T2DM) increases both the patient risk of cardiovascular disease (CVD) and renal outcomes, such as chronic kidney disease (CKD). Recent clinical trials of the glucose-lowering drug-class of sodium-glucose co-transporter-2 inhibitors (SGLT2is) have shown benefits in preventing CVD events and progression of CKD, leading to an update of the Dutch T2DM treatment guideline for patients at risk. The aim of this study is to assess the health and economic impact of the guideline-recommended utilization of SGLT2is in the Netherlands. METHODS: The patient population at risk was determined by multiplying Dutch T2DM prevalence rates with the total numbers of inhabitants of the Netherlands in 2020. Subsequently, two analyses, comparing a treatment setting before and after implementation of the new guideline for SGLT2is, were conducted. Clinical and adverse event rates in both settings as well as direct healthcare costs were sourced from the literature. Total costs were calculated by multiplying disease prevalence, event rates and costs associated to outcomes. One-time disutilities per event were included to estimate the health impact. The potential health and economic impact of implementing the updated guideline was calculated. RESULTS: Using a 5-year time horizon, the guideline-suggested utilization of SGLT2is resulted in a health impact equal to 4835 quality adjusted life years gained (0.0031 per patient per year) and €461 million cost-savings. The costs of treatment with SGLT2is were €813 million. Hence the net budget impact was €352 million for the total Dutch T2DM population, which translated to €0,57 per patient per day. CONCLUSION: SGLT2is offer an option to reduce the number of CVD and CKD related events and associated healthcare costs and health losses in the Netherlands. Further research is needed to include the benefits of improved T2DM management options from a broader societal perspective.HighlightsThe glucose-lowering drug-class of sodium-glucose co-transporter-2 inhibitors (SGLT2is) has shown benefits in preventing cardiovascular events and progression of kidney disease in patients with type-2 diabetes leading to a revision of the respective Dutch treatment guideline.The 5-year budget impact of the adoption of SGLT2is in the new treatment guideline was equal to €352 million or €0.57 per patient per day, with a total of 4385 quality adjusted life years gained.The introduction of SGLT2is for Dutch type-2 diabetes patients has the potential to substantially reduce the number of cardiovascular as well as renal disease events and related healthcare costs while also delivering a health benefit.

New Therapeutic Horizons in Chronic Kidney Disease: The Role of SGLT2 Inhibitors in Clinical Practice.

Chronic kidney disease (CKD) is a serious, progressive condition associated with significant patient morbidity. Hypertension control and use of renin-angiotensin system blockers are the cornerstones of treatment for CKD. However, even with these treatment strategies, many individuals will progress towards kidney failure. Recently, sodium-glucose cotransporter 2 (SGLT2) inhibitor clinical trials with primary renal endpoints have firmly established SGLT2 inhibition, in addition to standard of care, as an effective strategy to slow down the progression of CKD and reduce some of its associated complications. The emergence of this new clinical evidence supports the use of SGLT2 inhibitors in the management of CKD in people with and without diabetes. As licensing and guidelines for SGLT2 inhibitors are updated, there is a need to adapt CKD treatment pathways and for this class of drugs to be included as part of standard care for CKD management. In this article, we have used consensus opinion alongside the available evidence to provide support for the healthcare community involved in CKD management, regarding the role of SGLT2 inhibitors in clinical practice. By highlighting appropriate prescribing and practical considerations, we aim to encourage greater and safe use of SGLT2 inhibitors for people with CKD, both with and without diabetes.

Cost-effectiveness evaluation of add-on dapagliflozin for heart failure with reduced ejection fraction from perspective of healthcare systems in Asia-Pacific region.

BACKGROUND: With emerging evidence on the efficacy of adding dapagliflozin to standard care for patients with heart failure with reduced ejection fraction (HFrEF), this study assessed the cost-effectiveness of add-on dapagliflozin to standard care versus standard care alone for HFrEF from the perspective of healthcare systems in the Asia-Pacific region. METHODS: A Markov model was applied to project the outcomes of treatment in terms of lifetime medical cost and quality-adjusted life-years. The transition probabilities between health states in the model were obtained from the Dapagliflozin in Patients with Heart Failure and Reduced Ejection Fraction trial. Country-specific costs and utilities were extracted for modeling. The incremental cost-effectiveness ratio against a country-specific willingness-to-pay threshold was applied to determine the cost-effectiveness of treatment. A series of sensitivity analyses were performed to ensure the robustness of the study results. Costs are presented in 2020 United States dollars. RESULTS: The incremental cost-effectiveness ratios for add-on dapagliflozin versus standard care alone were $5277, $9980, $12,305, $16,705, and $23,227 per quality-adjusted life-year gained in Korea, Australia, Taiwan, Japan, and Singapore, respectively. When using add-on dapagliflozin to standard care versus standard care alone, ~ 100% of simulations were cost-effective at a willingness-to-pay threshold of one gross domestic product per capita of the given Asia-Pacific country; however, the probability of being cost-effective for using add-on dapagliflozin decreased when the time horizon for simulation was restricted to 18 months and when the cardiovascular mortality for the two treatments (43.8% and 33.0%, respectively) was assumed to be the same. The cost-effectiveness results were most sensitive to cardiovascular mortality of treatment. CONCLUSIONS: Adding dapagliflozin to standard care is cost-effective for HFrEF in healthcare systems in the Asia-Pacific region, which supports the rational use of dapagliflozin for HFrEF in this region.

Cost-effectiveness of Dapagliflozin for the Treatment of Heart Failure With Reduced Ejection Fraction.

Importance: Heart failure with reduced ejection fraction produces substantial morbidity, mortality, and health care costs. Dapagliflozin is the first sodium-glucose cotransporter 2 inhibitor approved for the treatment of heart failure with reduced ejection fraction. Objective: To examine the cost-effectiveness of adding dapagliflozin to guideline-directed medical therapy for heart failure with reduced ejection fraction in patients with or without diabetes. Design, Setting, and Participants: This economic evaluation developed and used a Markov cohort model that compared dapagliflozin and guideline-directed medical therapy with guideline-directed medical therapy alone in a hypothetical cohort of US adults with similar clinical characteristics as participants of the Dapagliflozin in Patients with Heart Failure and Reduced Ejection Fraction (DAPA-HF) trial. Dapagliflozin was assumed to cost $4192 annually. Nonparametric modeling was used to estimate long-term survival. Deterministic and probabilistic sensitivity analyses examined the impact of parameter uncertainty. Data were analyzed between September 2019 and January 2021. Main Outcomes and Measures: Lifetime incremental cost-effectiveness ratio in 2020 US dollars per quality-adjusted life-year (QALY) gained. Results: The simulated cohort had a starting age of 66 years, and 41.8% had diabetes at baseline. Median (interquartile range) survival in the guideline-directed medical therapy arm was 6.8 (3.5-11.3) years. Dapagliflozin was projected to add 0.63 (95% uncertainty interval [UI], 0.25-1.15) QALYs at an incremental lifetime cost of $42 800 (95% UI, $37 100-$50 300), for an incremental cost-effectiveness ratio of $68 300 per QALY gained (95% UI, $54 600-$117 600 per QALY gained; cost-effective in 94% of probabilistic simulations at a threshold of $100 000 per QALY gained). Findings were similar in individuals with or without diabetes but were sensitive to drug cost. Conclusions and Relevance: In this study, adding dapagliflozin to guideline-directed medical therapy was projected to improve long-term clinical outcomes in patients with heart failure with reduced ejection fraction and be cost-effective at current US prices. Scalable strategies for improving uptake of dapagliflozin may improve long-term outcomes in patients with heart failure with reduced ejection fraction.