Alexander T. Sandhu

Cost-Effectiveness of Sacubitril–Valsartan in Patients With Heart Failure With Reduced Ejection Fraction

Heart failure continues to cause substantial morbidity despite therapeutic advances over the past 3 decades (1). One of the cornerstones of therapy for heart failure with reduced ejection fraction is treatment with an angiotensin-converting enzyme inhibitor (ACEI) or an angiotensin-receptor blocker (ARB) to inhibit the reninangiotensinaldosterone system, a neurohormonal system that plays a large role in disease progression (2, 3). The natriuretic peptide system is a distinct neurohormonal system that induces positive hemodynamic effects in patients with heart failure. Sacubitrilvalsartan (Entresto [Novartis]) is a novel medication consisting of the ARB valsartan and sacubitril, a neprilysin inhibitor that decreases the degradation of natriuretic peptides. The PARADIGM-HF (Prospective Comparison of ARNI with ACEI to Determine Impact on Global Mortality and Morbidity in Heart Failure) trial was a randomized, double-blind trial that compared twice-daily treatment with sacubitrilvalsartan (200 mg) or enalapril (10 mg) in patients with chronic heart failure and reduced ejection fraction who were tolerating therapy with an ACEI or an ARB (4). It included a sequential run-in period before randomization, during which 10.5% of enrolled patients dropped out during the enalapril phase followed by 10.4% in the sacubitrilvalsartan phase. The trial randomly assigned 8442 patients and was stopped after a median follow-up of 27 months due to an overwhelming survival benefit. The study found that treatment with sacubitrilvalsartan reduced cardiovascular mortality, decreased hospitalizations and emergency department (ED) visits for heart failure, and improved quality of life compared with enalapril therapy (4, 5). However, at

Cost-Effectiveness of Implantable Pulmonary Artery Pressure Monitoring in Chronic Heart Failure

12.50 per day, sacubitrilvalsartan represents a substantial price increase compared with generic ACEIs that can cost less than 10 cents per day (6). We performed an independent analysis of the cost-effectiveness of sacubitrilvalsartan compared with usual care in a cohort of patients with New York Heart Association (NYHA) class II to IV heart failure based on the PARADIGM-HF trial population, as well as in subgroups defined by NYHA class. Methods Decision Model We developed a Markov model to evaluate the cost-effectiveness of sacubitrilvalsartan compared with lisinopril in patients at a mean age of 64 years, NYHA class II to IV heart failure, and reduced ejection fraction (<0.40), with a subgroup composition based on that of the PARADIGM-HF trial (72.9% with class II heart failure, 26.2% with class III, and 0.9% with class IV) (4, 7). We excluded patients with class I heart failure (4.7% of the trial population), who were unintentionally enrolled because they were more ill during screening and improved during the run-in phase; we included these patients in a sensitivity analysis (4, 7). We analyzed cost-effectiveness in the subgroups of patients with class II or class III/IV heart failure. We modeled a cohort of patients based on the PARADIGM-HF trial, which excluded patients with systolic blood pressure less than 95 to 100 mm Hg, chronic kidney disease (glomerular filtration rate <30 mL/min/1.73 m2), or inability to tolerate therapy during the run-in phase (4). Patients initially received sacubitrilvalsartan, 200 mg twice daily, or lisinopril, 20 mg daily (the target dose for heart failure). We modeled lisinopril instead of enalapril (the comparator in PARADIGM-HF) because it is less expensive, is more widely used, and has demonstrated functionally equivalent benefits compared with enalapril (6, 8, 9). In the model, patients incurred a monthly risk for heart failure hospitalization, nonheart failure hospitalization, ED visit for heart failure, treatment intolerance, and cardiovascular or noncardiovascular death (Appendix Figure 1). In addition, those with severe angioedema experienced a hospitalization. Patients with treatment intolerance during receipt of sacubitrilvalsartan were switched to lisinopril, and those with intolerance while receiving lisinopril were switched to the ARB losartan (100 mg/d). We used losartan as the alternative ARB therapy because it has effects similar to those of valsartan but lower cost (6, 8). We assumed that no patients would have intolerance of losartan or would discontinue its use. Appendix Figure 1. Model schema. The square is the treatment decision to start therapy with sacubitrilvalsartan or lisinopril (angiotensin-converting enzyme inhibitor). The Ms represent monthly models during which surviving patients are at risk for multiple events at chance nodes (circles): HF hospitalization, ED visits for HF without subsequent hospitalization, non-HF hospitalization (not shown), and death. Patients are also at risk for therapy intolerance, including angioedema, and death. The triangles signify the end of a monthly cycle and the initial state of the subsequent cycle. Surviving patients receiving sacubitrilvalsartan who have therapy intolerance switch to lisinopril the following month. Those receiving lisinopril with intolerance switch to losartan. ED = emergency department; HF = heart failure. The model followed patients over their lifetime with a monthly time cycle. We used a series of willingness-to-pay thresholds based on the cost-effectiveness guidelines of the American Heart Association and the World Health Organization, with less than

Cardiovascular Testing and Clinical Outcomes in Emergency Department Patients With Chest Pain

50000 per quality-adjusted life-year (QALY) (approximately the U.S. gross domestic product per capita) considered very cost-effective,

Sacubitril-Valsartan for the Treatment of Heart Failure: Effectiveness and Value

50000 to

CardioMEMS HF for the Management of Heart Failure—Effectiveness and Value

100000 per QALY representing intermediate value, and greater than

Telomere length in patients with systemic lupus erythematosus and its associations with carotid plaque

150000 per QALY (approximately 3 times the U.S. gross domestic product per capita) considered not cost-effective (10, 11). All costs and effects were discounted at 3% annually (12). We used a societal perspective, with inclusion of all health care costs regardless of payer, and adhered to best practices (12, 13). Event Probabilities Event probabilities, excluding therapy intolerance, were assumed to be the same in patients receiving lisinopril and those receiving losartan, given the absence of evidence for differences in effectiveness (14). We estimated event probabilities for the lisinopril and losartan groups from the event rates for the enalapril group in the PARADIGM-HF trial (Table 1) (47, 1520). Rates were adjusted to account for exclusion of the NYHA class I patients by using subgroup-specific estimates of events and follow-up. Alternative estimates of follow-up were tested in sensitivity analyses (see the Supplement, for details). We adjusted cardiovascular and noncardiovascular mortality to increase with age and calibrated to mortality rates over the trial duration (21, 22). Supplement. Technical Appendix Table 1. Selected Model Inputs The probabilities of cardiovascular death, heart failure hospitalization, and ED visits for patients receiving sacubitrilvalsartan were based on the event rate in the lisinopril group and calculated rate ratios between groups. The trials subgroup-specific hazard ratio (HR) was used for cardiovascular death (see the Supplement for details). Nonheart failure hospitalization and noncardiovascular mortality probabilities for all patients were based on the trial event rates in both groups combined. The probabilities of treatment intolerance and severe angioedema were based on the rates from each group of the trial. We assumed that losartan therapy had no associated intolerance or angioedema. Costs Costs of all 3 treatments were estimated using wholesale acquisition costs from the Red Book (6). The wholesale acquisition cost is the manufacturers national list price, subject to both discounts and dispensing premiums (23). The range of prices tested in deterministic sensitivity analyses was based on the minimum and maximum observed wholesale acquisition prices of a package of 90 pills for both lisinopril and losartan (Table 2). Table 2. Health and Economic Outcomes of SacubitrilValsartan Versus Lisinopril Therapy For sacubitrilvalsartan, the range was set to 50% of the base case (

Heart failure management with ambulatory pulmonary artery pressure monitoring

12.50 per day) due to the lack of variation in listed wholesale acquisition cost and the uncertainty about discounts and markups. We also tested estimates for specific payer groups whose average price varies (see the Supplement for details) (23). The cost of heart failure hospitalization was derived from the Agency for Healthcare Research and Qualitys National Inpatient Sample along with 2015 Medicare professional fees (17, 20). The costs of medication intolerance and severe angioedema were set to the Medicare reimbursements for a primary care appointment (17) and an anaphylaxis hospitalization (24), respectively. Additional health care costs were adjusted for age and NYHA class (25). Further details are provided in the Supplement. Utilities The baseline utility was based on the average EuroQol-5D baseline measurement for the enalapril group in the PARADIGM-HF trial (18). The incremental utility of patients receiving sacubitrilvalsartan was based on the average least-squares mean of the difference between the changes from baseline in the 2 groups (18, 19). Disutilities were applied for heart failure hospitalization and nonheart failure hospitalization, which were approximately equivalent to 3 days (16). In an alternative scenario analysis, we modeled long-term disutility secondary to heart failure hospitalizations (26). Additional disutilities are described in the Supplement. Additional Sensitivity Analysis We evaluated the uncertainty of all parameters using 1-way sensitivity analyses in the entire cohort along with NYHA subgroups. We also performed 2-way sensitivity analyses on potentially correlated variables, including baseline event probabilities and effectiveness of sacubitrilvalsartan. We conducted 2 additional scenario analyses. First, we modeled treatment initiation and initial intolerance based on data from the run-in period of PARADIGM-HF. The cost of starting therapy was assumed to be equivalent to a clin

Association Between Offering Limited Left Ventricular Ejection Fraction Echocardiograms and Overall Use of Echocardiography

OBJECTIVES This study aimed to evaluate the cost-effectiveness of the CardioMEMS (CardioMEMS Heart Failure System, St Jude Medical Inc, Atlanta, Georgia) device in patients with chronic heart failure. BACKGROUND The CardioMEMS device, an implantable pulmonary artery pressure monitor, was shown to reduce hospitalizations for heart failure and improve quality of life in the CHAMPION (CardioMEMS Heart Sensor Allows Monitoring of Pressure to Improve Outcomes in NYHA Class III Heart Failure Patients) trial. METHODS We developed a Markov model to determine the hospitalization, survival, quality of life, cost, and incremental cost-effectiveness ratio of CardioMEMS implantation compared with usual care among a CHAMPION trial cohort of patients with heart failure. We obtained event rates and utilities from published trial data; we used costs from literature estimates and Medicare reimbursement data. We performed subgroup analyses of preserved and reduced ejection fraction and an exploratory analysis in a lower-risk cohort on the basis of the CHARM (Candesartan in Heart failure: Reduction in Mortality and Morbidity) trials. RESULTS CardioMEMS reduced lifetime hospitalizations (2.18 vs. 3.12), increased quality-adjusted life-years (QALYs) (2.74 vs. 2.46), and increased costs (

Original InvestigationEditorial CommentUsing Commercial Programs for Lifestyle Intervention: Not Reinventing the Wheel∗

176,648 vs.

Using Commercial Programs for Lifestyle Intervention: Not Reinventing the Wheel∗

156,569), thus yielding a cost of