Budget Impact Analysis of Vericiguat for the Treatment of Chronic Heart Failure with Reduced Ejection Fraction Following a Worsening Event.
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ABSTRACT: Introduction
In the USA, patients with chronic heart failure (HF) with reduced ejection fraction (HFrEF) following a worsening HF event (WHFE) have significantly increased healthcare resource use and medical costs. This analysis aimed to estimate the budget impact of vericiguat as an add-on therapy to guideline-directed medical therapy (GDMT) for the treatment of chronic HFrEF following a WHFE from a US commercial payer perspective.Methods
A model was developed to estimate the budget impact of adding vericiguat to the formulary by comparing a current scenario (GDMT) and a new scenario (vericiguat plus GDMT) to a hypothetical 10-million-member commercial payer over a 3-year time horizon. Epidemiology data was obtained from literature. Treatment utilization rates of GDMT and clinical inputs (HF hospitalization and cardiovascular [CV] morality) were based on the VICTORIA trial in which patients with chronic HFrEF following a WHFE were randomized to GDMT plus placebo or GDMT plus vericiguat. Costs (2020 US$) included drug acquisition, hospitalization, routine care, and mortality.Results
Approximately 20,510 prevalent cases in year 1 and 3109 annual incident cases in subsequent years were estimated to be eligible for treatment with vericiguat. At a utilization rate of 5%, 10%, and 15% for vericiguat over years 1-3, the per member per month (PMPM) budget impact was estimated to be $0.048, $0.064, and $0.086, respectively, associated with 44, 32, and 30 fewer HF hospitalizations and 7, 12, and 18 fewer CV deaths, respectively. Reduction in HF hospitalizations and CV deaths reduced the budget impact by 14% in total over 3 years.Conclusion
Adding vericiguat to commercial plan formulary was associated with limited budget impact, primarily driven by drug acquisition costs but partially offset by reduced cost of HF hospitalizations and CV deaths.
SUBMITTER: Alsumali A
PROVIDER: S-EPMC8107071 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:ObjectiveGiven the high economic burden of disease among adult patients with chronic heart failure with reduced ejection fraction (HFrEF) following a worsening heart failure event in the US, this study aimed to estimate the cost effectiveness of vericiguat plus prior standard-of-care therapies (PSoCT) versus PSoCT alone from a US Medicare perspective.MethodsA four-state Markov model (alive prior to heart failure hospitalization, alive during heart failure hospitalization, alive post-heart failure hospitalization, and death) was developed to predict clinical and economic outcomes, based on the results of the VICTORIA trial, in which patients with chronic HFrEF following a worsening heart failure were randomized to placebo or vericiguat, in addition to PSoCT, which consisted of β-blockers, renin-angiotensin-aldosterone inhibitors, mineralocorticoid receptor antagonists, and the angiotensin receptor-neprilysin inhibitor sacubitril/valsartan. Risks of heart failure hospitalization and cardiovascular mortality were based on multivariable regression models derived from VICTORIA data. Utilities were derived from VICTORIA EQ-5D data and the literature. Costs included drug acquisition, heart failure hospitalization, routine care, and terminal care. Primary outcomes included heart failure hospitalization, cardiovascular mortality, life-years, quality-adjusted life-years (QALYs), and incremental costs per QALY gained over a 30-year lifetime horizon, discounted at 3.0% annually.ResultsFor the VICTORIA overall intent-to-treat population, compared with PSoCT, vericiguat plus PSoCT resulted in 19 fewer heart failure hospitalizations and 13 fewer cardiovascular deaths per 1000 patients, as well as 0.28 QALY gained per patient at an incremental cost of $23,322, leading to $82,448 per QALY gained.ConclusionsBased on the results of VICTORIA, patients treated with vericiguat had lower rates of heart failure hospitalization and cardiovascular death. The addition of vericiguat to PSoCT was estimated to increase QALYs and to be cost effective at a willingness-to-pay threshold of $100,000 per QALY gained.
| S-EPMC8516766 | biostudies-literature
Project description:IntroductionA worsening heart failure event (WHFE) is defined as progressively escalating heart failure signs/symptoms requiring intravenous diuretic treatment or hospitalization. No studies have compared the burden of chronic heart failure with reduced ejection fraction (HFrEF) following a WHFE versus stable disease to inform healthcare decision makers.MethodsA retrospective study using the IBM® MarketScan® Commercial Database included patients younger than 65 years of age with HFrEF (one inpatient or two outpatient claims of systolic HF or one outpatient claim of systolic HF plus one outpatient claim of any HF). The first claim for HFrEF during 2016 was the index date. Patients were followed for the first 12 months after the index date (the worsening assessment period) to identify a WHFE, and for an additional 12 months or until the end of continuous enrollment (the post-worsening assessment period). Mean per patient per month (PPPM) health care resource use (HCRU) and costs were compared between patients following a WHFE and stable patients during the two periods using generalized linear models adjusting for patient characteristics.ResultsOf 16,646 patients with chronic HFrEF, 26.8% developed a WHFE. Adjusted all-cause hospitalizations (0.16 vs. 0.02 PPPM, P < 0.0001), outpatient visits (3.54 vs. 2.73 PPPM, P < 0.0001), and emergency department visits (0.25 vs. 0.06 PPPM, P < 0.0001) were higher in patients following a WHFE than stable patients during the worsening assessment period. Similar differences in HCRU were observed between the two cohorts during the post-worsening assessment period. Mean total adjusted cost of care PPPM was $8657 in patients with HFrEF following a WHFE versus $2195 in stable patients during the worsening assessment period, and $6809 versus $2849, respectively, during the post-worsening assessment period.ConclusionHCRU and costs were significantly greater in patients with chronic HFrEF following a WHFE compared to those who remained stable, suggesting an unmet need to improve clinical and economic outcomes among these patients.
| S-EPMC7444407 | biostudies-literature
Project description:AimsThe aim of this study is to characterize healthcare resource utilization and costs in patients with heart failure with reduced ejection fraction (HFrEF) following a worsening heart failure event.Methods and resultsThis was a retrospective observational cohort analysis. Patients with HFrEF were identified from the PINNACLE Registry and linked to a nationwide pharmacy and medical claims database. Worsening heart failure was defined as stable heart failure with a subsequent hospitalization and/or intravenous diuretic therapy. Healthcare resource use and costs in 2015 US dollars were analysed for dispensed prescriptions, outpatient encounters, and hospital encounters. Among 11 064 patients with HFrEF, 3087 (27.9%) experienced a worsening heart failure event during an average follow-up of 973 days. During the first 30 days after the worsening event, 19.8% of patients had hospital readmissions with heart failure as the primary or secondary diagnosis. During that same time period, mean per patient heart failure-related healthcare resource use included 1.3 prescriptions, 0.5 practitioner visits, and 0.5 hospital encounters (admissions, observations, or emergency care), for an average total medical cost of $8779 per patient including $5359 in heart failure-related costs. During the first year following worsening heart failure onset, mean per patient total and heart failure-related costs were $62 615 and $35 329, respectively.ConclusionsThe economic burden following a worsening heart failure event calls for further review of methods to prevent progressive disease, improve adherence to guideline-directed therapy, and develop novel treatments and care strategies to moderate further progression.
| S-EPMC8120411 | biostudies-literature
Project description:Heart failure with reduced ejection fraction is a chronic and progressive syndrome that continues to be a substantial financial burden for health systems in Western countries. Despite remarkable advances in pharmacologic and device-based therapy over the last few years, patients with heart failure with reduced ejection fraction have a high residual risk of adverse outcomes, even when treated with optimal guideline-directed medical therapy and in a clinically stable state. Worsening heart failure episodes represent a critical event in the heart failure trajectory, carrying high residual risk at discharge and dismal short- or long-term prognosis. Recently, vericiguat, a soluble guanylate cyclase stimulator, has been proposed as a novel drug whose use is already associated with a reduction in heart failure-related hospitalizations in patients in guideline-directed medical therapy. In this review, we summarized the pathophysiology of the nitric oxide-soluble guanylate cyclase-cyclic guanosine monophosphate cascade in patients with heart failure with reduced ejection fraction, the pharmacology of vericiguat as well as the evidence regarding their use in patients with HFrEF. Finally, tips and tricks for its use in standard clinical practice are provided.
| S-EPMC10531735 | biostudies-literature
Project description:Background Contemporary trials of patients with heart failure with reduced ejection fraction (HFrEF) required a recent worsening heart failure (WHF) event for inclusion. We aimed to describe characteristics and outcomes of patients with HFrEF and a recent WHF event at a large tertiary referral center. Methods and Results We identified adult patients with chronic symptomatic HFrEF (ejection fraction ≤35%) treated at Duke University between January 1, 2009, and December 31, 2018, and applied a set of exclusion criteria to generate a cohort similar to those enrolled in contemporary heart failure trials. Patients were stratified by presence or absence of a recent WHF event, defined as an emergency department visit for heart failure or hospitalization for heart failure in the prior 12 months. Characteristics and outcomes including death and hospitalization were assessed. Of 3867 patients with HFrEF meeting study criteria, 2823 (73.0%) had a WHF event in the prior 12 months. Compared with patients without a WHF event, those with a WHF event were more likely to be under-represented racial and ethnic groups and had lower ejection fraction, a greater burden of comorbidities, and more echocardiographic evidence of cardiac dysfunction. Despite higher use of guideline-directed therapies, patients with a WHF event had higher rates of death (hazard ratio, 2.30; 95% CI, 2.01-2.63), all-cause hospitalization (hazard ratio, 1.56; 95% CI, 1.42-1.71), and heart failure hospitalization (hazard ratio, 1.59; 95% CI, 1.44-1.75) through 5 years compared with those without a recent WHF event. Conclusions WHF events are common in patients with HFrEF and are associated with more advanced disease. Patients with recent WHF have high rates of death and hospitalization, underscoring the need for novel therapies in this large subgroup of patients with HFrEF.
| S-EPMC8649225 | biostudies-literature
Project description:BackgroundVericiguat, a stimulator of soluble guanylate cyclase, has been developed as a first-in-class therapy for worsening chronic heart failure in adults with left ventricular ejection fraction < 45%.ObjectiveThe objective of this article was to characterize the pharmacokinetics and pharmacokinetic variability of vericiguat combined with guideline-directed medical therapy (standard of care), and identify exposure-response relationships for safety (hemodynamics) and pharmacodynamic markers of efficacy (N-terminal pro-B-type natriuretic peptide concentration [NT-proBNP]) in patients with heart failure and left ventricular ejection fraction < 45% in the SOCRATES-REDUCED study (NCT01951625).MethodsVericiguat and NT-proBNP plasma concentrations in 454 and 432 patients in SOCRATES-REDUCED, respectively, were analyzed using nonlinear mixed-effects modeling.ResultsVericiguat pharmacokinetics were well described by a one-compartment model with apparent clearance, apparent volume of distribution, and absorption rate constant. Age, bodyweight, plasma bilirubin, and creatinine clearance were identified as significant covariates on apparent clearance; sex and bodyweight on apparent volume of distribution; and bodyweight and plasma albumin level on absorption rate constant. Pharmacokinetic/pharmacodynamic analysis showed initial minor and transient effects of vericiguat on blood pressure with low clinical impact. There were no changes in heart rate following initial or repeated vericiguat administration. An exposure-dependent and time-dependent turnover pharmacokinetic/pharmacodynamic model for NT-proBNP described production and elimination rates and an demonstrated exposure-dependent reduction in [NT-proBNP] by vericiguat plus standard of care compared with placebo plus standard of care. This effect was dependent on baseline [NT-proBNP].ConclusionsVericiguat has predictable pharmacokinetics, with no long-term effects on blood pressure in patients with heart failure and left ventricular ejection fraction < 45%. A pharmacokinetic/pharmacodynamic model described a vericiguat exposure-dependent reduction of NT-proBNP.Clinical trial identifierNCT01951625.
| S-EPMC8585847 | biostudies-literature
Project description:AimsVericiguat reduced the primary composite outcome of cardiovascular death or heart failure (HF) hospitalization in patients with worsening HF with reduced ejection fraction (HFrEF) and a lower limit of baseline estimated glomerular filtration rate (eGFR) of 15 mL/min/1.73 m2 . We evaluated the relationship between the efficacy of vericiguat and baseline and subsequent changes in renal function.Methods and resultsIn VICTORIA, core laboratory serum creatinine was measured at baseline (n = 4956) and weeks 16, 32, and 48. Worsening renal function (WRF), defined as an increase ≥0.3 mg/dL in creatinine from baseline to week 16, was assessed via a Cox model with respect to subsequent primary events. Mean age was 69 years, 24% were female, and mean baseline eGFR was 61 mL/min/1.73 m2 . During 48 weeks of treatment, the trajectories in eGFR and creatinine with vericiguat were similar to placebo (P = 0.50 and 0.18). The beneficial effects of vericiguat on the primary outcome were not influenced by baseline eGFR (interaction P = 0.48). WRF occurred in 15% of patients and was associated with worse outcomes (adjusted hazard ratio 1.28, 95% confidence interval 1.11-1.47; P < 0.001), but the beneficial effects of vericiguat on the primary outcome were similar in patients with or without WRF (interaction P = 0.76).ConclusionRenal function trajectories were similar between vericiguat- and placebo-treated patients and the beneficial effects of vericiguat on the primary outcome were consistent across the full range of eGFR and irrespective of WRF.
| S-EPMC8453520 | biostudies-literature
Project description:AimsTreatment response to vericiguat, based on baseline N-terminal pro-brain natriuretic peptide (NT-proBNP) subgroups specified in the protocol, was evaluated in the heart failure (HF) VICTORIA trial population by post hoc analysis of combined lower three quartiles [Q1-Q3] vs. the upper quartile [Q4].Methods and resultsVICTORIA participants with available baseline NT-proBNP levels (n = 4805; 95.1% of total) were included. Compared with patients in Q1-Q3 (NT-proBNP: Q1, ≤1556 pg/mL; Q2, >1556-2816 pg/mL; and Q3, >2816-5314 pg/mL), patients in Q4 (NT-proBNP: >5314 pg/mL) were older (69.2 ± 12.0 vs. 66.6 ± 12.1 years), had lower mean ejection fraction (27.2 ± 8.3% vs. 29.5 ± 8.2%; P < 0.0001), and were more likely to be in New York Heart Association (NYHA) Class III (51.8 vs. 35.6%) or IV (2.4 vs. 1.0%). Compared with Q1-Q3, patients in Q4 had higher mean Meta-Analysis Global Group in Chronic Heart Failure risk score (27.3 ± 6.6 vs. 23.5 ± 6.4; P < 0.0001), had lower mean estimated glomerular filtration rate (eGFR; 51.5 ± 25.5 vs. 65.0 ± 26.8 mL/min/1.73 m2 ; P < 0.0001) and haemoglobin (12.8 ± 2.0 vs. 13.6 ± 1.9 g/dL; P < 0.0001), and more had atrial fibrillation (48.7% vs. 43.1%; P = 0.0007) and were randomized while hospitalized for HF (14.8 vs. 9.9%; P < 0.0001). Target dose was achieved in 72.3 and 63.7% of patients in Q1-Q3 and Q4, respectively (P < 0.0001). Primary outcome (composite of time to cardiovascular death or first HF hospitalization) rates were 24.5 and 31.7 per 100 patient-years for vericiguat and placebo in Q1-Q3 [hazard ratio (HR) 0.78; 95% confidence interval (CI) 0.69-0.88, P < 0.001] and 73.6 and 63.6 in Q4 (HR 1.15; 95% CI 0.99-1.34, P = 0.070). Serious adverse events were more frequent in NT-proBNP Q4 (total population) compared with Q1-Q3 (38.3 vs. 32.3%; P = 0.0001), driven mainly by the placebo group. Adverse events leading to death were more frequent in Q4 than Q1-Q3 (5.8 vs. 2.4%; P < 0.0001).ConclusionsPlasma NT-proBNP may help identify patients with worsening HF with reduced ejection fraction, in whom the beneficial effects of vericiguat may be highest. Patients with highest NT-proBNP values are probably too far advanced, suffering more co-morbidities, or still clinically unstable after decompensation to derive benefit from vericiguat.
| S-EPMC9773767 | biostudies-literature
Project description:BackgroundHospitalization is recognized as a sentinel event in the disease trajectory of patients with heart failure (HF), but not all patients experiencing clinical decompensation are ultimately hospitalized. Outpatient intensification of diuretics is common in response to symptoms of worsening HF, yet its prognostic and clinical relevance, specifically for patients with HF with mildly reduced or preserved ejection fraction, is uncertain.MethodsIn this prespecified analysis of the DELIVER trial (Dapagliflozin Evaluation to Improve the Lives of Patients With Preserved Ejection Fraction Heart Failure), we assessed the association between various nonfatal worsening HF events (those requiring hospitalization, urgent outpatient visits requiring intravenous HF therapies, and outpatient oral diuretic intensification) and rates of subsequent mortality. We further examined the treatment effect of dapagliflozin on an expanded composite end point of cardiovascular death, HF hospitalization, urgent HF visit, or outpatient oral diuretic intensification.ResultsIn DELIVER, 4532 (72%) patients experienced no worsening HF event, whereas 789 (13%) had outpatient oral diuretic intensification, 86 (1%) required an urgent HF visit, 585 (9%) had an HF hospitalization, and 271 (4%) died of cardiovascular causes as a first presentation. Patients with a first presentation manifesting as outpatient oral diuretic intensification experienced rates of subsequent mortality that were higher (10 [8-12] per 100 patient-years) than those without a worsening HF event (4 [3-4] per 100 patient-years) but similar to rates of subsequent death after an urgent HF visit (10 [6-18] per 100 patient-years). Patients with an HF hospitalization as a first presentation of worsening HF had the highest rates of subsequent death (35 [31-40] per 100 patient-years). The addition of outpatient diuretic intensification to the adjudicated DELIVER primary end point (cardiovascular death, HF hospitalization, or urgent HF visit) increased the overall number of patients experiencing an event from 1122 to 1731 (a 54% increase). Dapagliflozin reduced the need for outpatient diuretic intensification alone (hazard ratio, 0.72 [95% CI, 0.64-0.82]) and when analyzed as a part of an expanded composite end point of worsening HF or cardiovascular death (hazard ratio, 0.76 [95% CI, 0.69-0.84]).ConclusionsIn patients with HF with mildly reduced or preserved ejection fraction, worsening HF requiring oral diuretic intensification in ambulatory care was frequent, adversely prognostic, and significantly reduced by dapagliflozin.RegistrationURL: https://www.clinicaltrials.gov; Unique identifier: NCT03619213.
| S-EPMC10664793 | biostudies-literature
Project description:AimsThis study aimed to investigate the prognostic value of dynamic changes in left ventricular ejection fraction (EF) for cardiovascular (CV) outcomes in an all-comer heart failure (HF) population with reduced EF (HFrEF, EF < 40%). We sought to identify independent factors related to improvement in EF and to identify risk factors for increased risk of CV events in the subgroups of improved EF (iEF) and non-improved EF (niEF), respecively.Methods and resultsThis is a retrospective sub-analysis from the REDEAL HF trial, which included consecutive patients with chronic HF who were hospitalized from July 2009 to December 2017. Baseline and follow-up echocardiography data (interval ≥12 months) of 573 consecutive patients with HFrEF were analysed. iEF was defined as absolute improvement in EF ≥ 10% and follow-up EF over 40%. The primary endpoint was defined as a composite endpoint of cardiovascular (CV) death, CV hospitalization, or appropriate implantable cardioverter-defibrillator (ICD) therapy for ventricular arrhythmia. EF improved in 37.2% of patients with HFrEF during follow-up (median period of 17 months). iEF was independently associated with shorter HF duration (>4 vs. ≤4 years, odd ratio [OR] = 0.477, 95% CI 0.305-0.745), no coronary artery disease (CAD vs. no CAD, OR = 0.583, 95% CI 0.396-0.858), and no ICD implantation (ICD vs. no ICD, OR = 0.341, 95% CI 0.228-0.511). Compared with niEF, iEF was significantly and independently associated with lower all-cause mortality (22.1% vs. 31.1%, P = 0.019; hazard ratio [HR] = 0.674, 95% CI 0.469-0.968), lower CV mortality (8.9% vs. 16.1%, P = 0.015; HR = 0.539, 95% CI 0.317-0.916), and lower CV events risk (27.2% vs. 49.2%, P < 0.001; HR 0.519, 95% CI 0.381-0.708), after adjustment for age, sex, duration of HF, and other clinical risk factors. Hypertension (HR = 2.452, P = 0.032) and elevated N-terminal prohormone of brain natriuretic peptide (NT-proBNP >1153 pg/mL, HR = 4.372, P < 0.001) were identified as independent risk factors for CV events in the iEF subgroup. ICD implantation (HR = 1.533, P = 0.011), elevated NT-proBNP (HR = 1.626, P = 0.018), increased left atrial volume index (HR = 1.461, P = 0.021), reduced lateral mitral annular plane systolic excursion (HR = 1.478, P = 0.025), and reduced tricuspid plane systolic excursion (HR = 1.491, P = 0.039) were identified as risk factors for CV events in the niEF subgroup.ConclusionsImprovement in EF is independently related to the longer survival and lower CV related mortality and hospitalization rate of HFrEF. Elevated baseline NT-proBNP is identified as the strongest prognostic factor associated with increased CV events risk in HFrEF patients both with and without improved EF, regardless of age, sex, duration of HF, and other clinical risk factors.
| S-EPMC10053299 | biostudies-literature