Celine Deschaseaux

Thirty Years of Evidence on the Efficacy of Drug Treatments for Chronic Heart Failure With Reduced Ejection Fraction: A Network Meta-Analysis.

Background— Treatments that reduce mortality and morbidity in patients with heart failure with reduced ejection fraction, including angiotensin-converting enzyme inhibitors (ACEI), angiotensin receptor blockers (ARB), &bgr;-blockers (BB), mineralocorticoid receptor antagonists (MRA), and angiotensin receptor–neprilysin inhibitors (ARNI), have not been studied in a head-to-head fashion. This network meta-analysis aimed to compare the efficacy of these drugs and their combinations regarding all-cause mortality in patients with heart failure with reduced ejection fraction. Methods and Results— A systematic literature review identified 57 randomized controlled trials published between 1987 and 2015, which were compared in terms of study and patient characteristics, baseline risk, outcome definitions, and the observed treatment effects. Despite differences identified in terms of study duration, New York Heart Association class, ejection fraction, and use of background digoxin, a network meta-analysis was considered feasible and all trials were analyzed simultaneously. The random-effects network meta-analysis suggested that the combination of ACEI+BB+MRA was associated with a 56% reduction in mortality versus placebo (hazard ratio 0.44, 95% credible interval 0.26–0.66); ARNI+BB+MRA was associated with the greatest reduction in all-cause mortality versus placebo (hazard ratio 0.37, 95% credible interval 0.19–0.65). A sensitivity analysis that did not account for background therapy suggested that ARNI monotherapy is more efficacious than ACEI or ARB monotherapy. Conclusions— The network meta-analysis showed that treatment with ACEI, ARB, BB, MRA, and ARNI and their combinations were better than the treatment with placebo in reducing all-cause mortality, with the exception of ARB monotherapy and ARB plus ACEI. The combination of ARNI+BB+MRA resulted in the greatest mortality reduction.

Treatment Initiation Patterns, Modifications, and Medication Adherence Among Newly Diagnosed Heart Failure Patients: A Retrospective Claims Database Analysis

BACKGROUND Heart failure (HF) is a debilitating disease associated with high mortality and frequent hospitalizations. American College of Cardiology Foundation and American Heart Association (ACCF/AHA) guidelines recommend the following drug classes for HF treatment: angiotensin-converting enzyme inhibitor (ACEI), angiotensin receptor II blocker (ARB) for patients intolerant to ACEI, beta blocker (BB), and aldosterone antagonist (AA). OBJECTIVE To examine, in a real-word setting, the treatment initiation pattern among newly diagnosed HF patients in the United States, subsequent treatment modifications, hospitalizations and the impact of hospitalizations on therapy changes, and treatment adherence and persistence. METHODS Using medical and pharmacy claims data from the Truven Health MarketScan database, this retrospective cohort study included adult patients with ≥ 2 medical claims corresponding to an HF diagnosis (ICD-9-CM codes 428.x, 402.11, 402.91, 404.01, 404.11, 404.91, 404.03, 404.13, and 404.93) between April 2009 and March 2012. The date of the first claim was defined as the index date. Patients with continuous medical and pharmacy eligibility for a minimum of 12 months pre- and post-index were included in the analysis. Patients with an HF diagnosis in the 12 months before the index date were excluded. Index treatment (within 30 days post-index), subsequent treatment modification (class addition/removal) during the study period, hospitalization, and change in treatment after hospitalization (within 15 days after hospital discharge) were determined. Adherence was evaluated using the proportion of days covered (PDC) method, and persistence was defined as the proportion of patients remaining on index treatment after a defined period of time (12 months). RESULTS A total of 235,758 patients meeting the sample selection criteria were included in the analysis and were followed for a median of 28 months after the index date. Approximately 42% of patients were not prescribed any HF-specific treatment within 30 days post-index. Among those treated, prescriptions for ACEIs were filled by 46.42% of patients, ARBs by 17.07%, BBs by 75.62%, and AAs by 9.83%. Based on HF therapy class, monotherapy was prescribed to 51% of patients, bi-therapy to 40%, and triple therapy to 9%. More than 80% of patients experienced treatment modification during the median 28 months of follow-up. A total of 174,563 (74.0%) patients had at least 1 all-cause hospitalization (mean 1.11 [SD = 0.98]) per year, with a mean length of stay (LOS) of 7.19 [SD = 8.69] days. Within 12 months post-index, 85.7% of these patients experienced an all-cause hospitalization, with 29.6% having HF-related hospitalization (mean 0.18 [0.36]) and mean LOS of 5.85 [5.45] days. More than 60% of patients continued on the same therapy after all-cause or HF hospitalization. More patients on multiple therapies remained on the same treatment (73%-89%) compared with those treated with monotherapy (60%-73%) after the first HF hospitalization. Among patients untreated before hospitalization, 9.8% and 17% received treatment after all-cause and HF hospitalization, respectively. During the entire study period (median 28 months), 29% of patients did not have a prescription fill for HF-specific treatments. The median PDC was > 0.65, and considering a gap of 30 days between ends of supply from 1 medication fill to the subsequent fill, persistence ranged from 41% (AA) to 52% (BB). CONCLUSIONS Findings of this claims database analysis among 235,758 HF patients suggest that more than one third of newly diagnosed HF patients do not receive HF-specific medication within 30 days following initial diagnosis. Despite ACCF/AHA recommendations of initiating treatment with a combination of 2 HF drug classes, only 40% of patients had a prescription fill for bi-therapy. Hospitalization did not have a major impact on HF therapy prescribing patterns. To our knowledge, this is the first study to establish the impact of hospitalization on HF-specific treatment among newly diagnosed patients. Adherence and persistence were moderate across all HF therapies of interest. This analysis reveals the need for further research to better understand the reasons for the demonstrated delay in HF treatment initiation and limited use of guideline-directed medical therapy after initial diagnosis. DISCLOSURES This study was funded by Novartis Pharma AG, Basel, Switzerland. Deschaseaux, McSharry, Hudson, Agrawal, and Turner are permanent employees of Novartis. Concept and study design were contributed by Deschaseaux, Hudson, and Turner, along with McSharry. McSharry took the lead in data collection, along with Deschaseaux, Hudson, and Turner. Data interpretation was performed by Hudson, along with the other authors. The manuscript was written by Agrawal, along with Deschaseaux and Turner, and revised by Deschaseaux and Turner, along with the other authors.

Cost-effectiveness of sacubitril/valsartan in the treatment of heart failure with reduced ejection fraction

Objective Chronic heart failure with reduced ejection fraction (HF-REF) represents a major public health issue and is associated with considerable morbidity and mortality. We evaluated the cost-effectiveness of sacubitril/valsartan (formerly LCZ696) compared with an ACE inhibitor (ACEI) (enalapril) in the treatment of HF-REF from the perspective of healthcare providers in the UK, Denmark and Colombia. Methods A cost-utility analysis was performed based on data from a multinational, Phase III randomised controlled trial. A decision-analytic model was developed based on a series of regression models, which extrapolated health-related quality of life, hospitalisation rates and survival over a lifetime horizon. The primary outcome was the incremental cost-effectiveness ratio (ICER). Results In the UK, the cost per quality-adjusted life-year (QALY) gained for sacubitril/valsartan (using cardiovascular mortality) was £17 100 (€20 400) versus enalapril. In Denmark, the ICER for sacubitril/valsartan was Kr 174 000 (€22 600). In Colombia, the ICER was COP

A New Cost-Effectiveness Modelling Approach In Chronic Heart Failure With Reduced Ejection Fraction

39.5 million (€11 200) per QALY gained. Deterministic sensitivity analysis showed that results were most sensitive to the extrapolation of mortality, duration of treatment effect and time horizon, but were robust to other structural changes, with most scenarios associated with ICERs below the willingness-to-pay threshold for all three country settings. Probabilistic sensitivity analysis suggested the probability that sacubitril/valsartan was cost-effective at conventional willingness-to-pay thresholds was 68%–94% in the UK, 84% in Denmark and 95% in Colombia. Conclusions Our analysis suggests that, in all three countries, sacubitril/valsartan is likely to be cost-effective compared with an ACEI (the current standard of care) in patients with HF-REF.

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

Objectives: As new therapies for chronic heart failure with reduced ejection fraction (HFrEF) emerge, health technology assessments (HTAs) will require cost-effectiveness analyses to inform decision making. The objective was to develop a model framework for evaluating the cost-effectiveness of LCZ696, a novel oral therapy proposed for the treatment of HFrEF. Methods: A systematic literature review was performed. Searches were conducted in MEDLINE, EMBASE, EconLit, and Cochrane Library databases, with supplementary hand searching of conferences and HTA websites. Of 63 distinct analyses identified, 33 used decision-analytic models. Structures were most commonly described as Markov models (n=27), but methods employed were heterogeneous. The health states most frequently employed were ‘alive’ and ‘dead’, with outcomes such as hospitalization or New York Heart Association (NYHA) class distribution most commonly considered within the ‘alive’ state. Results: A 2-state Markov model with ‘alive’ and ‘dead’ states was developed using three multivariate regression models to predict the risks of mortality, hospitalisation and the trajectory of health-related quality of life over time within the ‘alive’ state. NYHA class was not used as a basis for health states, as the extrapolation of clinical improvements beyond the observed data was considered clinically implausible. Parametric survival models, negative binomial models and multilevel models are used to predict mortality, hospitalisation, and HRQL, respectively, allowing extrapolation to a lifetime time horizon. The model of HRQL attempts to capture the effects of baseline characteristics, hospitalisation, adverse events and time on EQ-5D. Clinical experts were consulted to validate the regression models and their respective predictions. Conclusions: The new framework employs similar methods to decision analytic models developed previously in heart failure, however models health-related quality of life as a function of time directly, thereby providing a parsimonious approach with improved clinical plausibility compared to other model structures in the literature.

Cost-effectiveness of sacubitril/valsartan in chronic heart-failure patients with reduced ejection fraction

Abstract 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.

GW24-e2140 Real-world resource utilisation and costs following hospitalisation of patients with heart failure and preserved ejection fraction in five regions of China

AIMS We aimed to assess the cost effectiveness of sacubitril/valsartan compared to angiotensin-converting enzyme inhibitors (ACEIs) for the treatment of individuals with chronic heart failure and reduced-ejection fraction (HFrEF) from the perspective of the Swiss health care system. METHODS The cost-effectiveness analysis was implemented as a lifelong regression-based cohort model. We compared sacubitril/valsartan with enalapril in chronic heart failure patients with HFrEF and New York-Heart Association Functional Classification II-IV symptoms. Regression models based on the randomised clinical phase III PARADIGM-HF trials were used to predict events (all-cause mortality, hospitalisations, adverse events and quality of life) for each treatment strategy modelled over the lifetime horizon, with adjustments for patient characteristics. Unit costs were obtained from Swiss public sources for the year 2014, and costs and effects were discounted by 3%. The main outcome of interest was the incremental cost-effectiveness ratio (ICER), expressed as cost per quality-adjusted life years (QALYs) gained. Deterministic sensitivity analysis (DSA) and scenario and probabilistic sensitivity analysis (PSA) were performed. RESULTS In the base-case analysis, the sacubitril/valsartan strategy showed a decrease in the number of hospitalisations (6.0% per year absolute reduction) and lifetime hospital costs by 8.0% (discounted) when compared with enalapril. Sacubitril/valsartan was predicted to improve overall and quality-adjusted survival by 0.50 years and 0.42 QALYs, respectively. Additional net-total costs were CHF 10 926. This led to an ICER of CHF 25 684. In PSA, the probability of sacubitril/valsartan being cost-effective at thresholds of CHF 50 000 was 99.0%. CONCLUSION The treatment of HFrEF patients with sacubitril/valsartan versus enalapril is cost effective, if a willingness-to-pay threshold of CHF 50 000 per QALY gained ratio is assumed.

The Caregiver Burden Questionnaire for Heart Failure (CBQ-HF): face and content validity

Objectives There are limited data on the humanistic and economic burden of heart failure with preserved ejection fraction (HFpEF) in China. Therefore, we aimed to collect real-world data on the resource utilisation, treatment patterns and costs of managing HFpEF in China. Methods A retrospective chart review was conducted in 10 hospitals in 5 regions of China (Beijing, Shanghai, Chengdu, Guangzhou, and Wuhan) to identify patients hospitalised for heart failure (HF) between 2005 and 2008. Charts were reviewed for healthcare treatment between 2000 and 2011 and data collected from the index HF hospitalisation to last date of entry or death. Results This study included 805 patients, of which 282 had HFpEF. Mean follow-up was 2.8 years. For patients with HFpEF, the mean age was 65 years and 57% were male. There was a high prevalence of hypertension (73%), and 31, 40, 21 and 8% of patients had New York Heart Association (NYHA) class I, II, III and IV HF, respectively, at index hospitalisation. For patients with HFpEF, 34% were rehospitalized following the index hospitalisation and the mean number of hospitalizations was 2.8. The mean length of stay for the index hospitalisation was 12 days, increasing to 18, 19 and 16 days for the second, third and fourth hospitalizations, respectively. The total cost of index hospitalisation was 27066 (US

PCV90 A Novel Conceptual Model of Caregiver Burden in Chronic Heart Failure: A Qualitative Study

3998), 18269 (US

Psychometric Validation of the Heart Failure Caregiver Questionnaire (HF-CQ ® )

2698) and 1039 (US