Cost-effectiveness of Empagliflozin in Patients With Heart Failure With Preserved Ejection Fraction.

Importance: In the Empagliflozin Outcome Trial in Patients With Chronic Heart Failure With Preserved Ejection Fraction (EMPEROR-Preserved), empagliflozin significantly reduced hospitalizations for heart failure while improving patient-reported health status compared with placebo. The long-term cost-effectiveness of empagliflozin among patients who have heart failure with preserved ejection fraction (HFpEF) remains unclear. Objective: To estimate the cost-effectiveness of empagliflozin in patients with HFpEF. Design, Setting, and Participants: This cost-effectiveness analysis performed from October 2021 to April 2022 included a Markov model using estimates of treatment efficacy, event probabilities, and utilities from EMPEROR-Preserved and published literature. Costs were derived from national surveys and pricing data sets. Quality of life was imputed from a heart failure-specific quality-of-life measure. Two analyses were performed, with and without a treatment effect on cardiovascular mortality. Subgroup analyses were based on diabetes status, ejection fraction, and health status impairment due to heart failure. The model reproduced the event rates and risk reduction with empagliflozin observed in EMPEROR-Preserved over 26 months of follow-up; future projections extended across the lifetime of patients. Exposures: Empagliflozin or standard of care. Main Outcomes and Measures: Hospitalizations for heart failure, life-years, quality-adjusted life-years (QALYs), lifetime costs, and lifetime incremental cost-effectiveness ratio. Results: A total of 5988 patients were included in the analysis, with a mean age of 72 years, New York Heart Association class II to IV heart failure, and left ventricular ejection fraction greater than 40%. At the Federal Supply Schedule price of $327 per month, empagliflozin yielded 0.06 additional QALYs and $26 257 incremental costs compared with standard of care, producing a cost per QALY gained of $437 442. Incremental costs consisted of total drug costs of $29 586 and savings of $3329 from reduced hospitalizations for heart failure. Cost-effectiveness was similar across subgroups. The results were most sensitive to the monthly cost, quality-of-life benefit, and mortality effect of empagliflozin. A price reduction to $153 per month, incremental utility of 0.02, or 8% reduction in cardiovascular mortality would bring empagliflozin to $180 000 per QALY gained, the threshold for intermediate value. Using Medicare Part D monthly pricing of $375 after rebates and $511 before rebates, empagliflozin would remain low value at $509 636 and $710 825 per QALY gained, respectively. Cost-effectiveness estimates were robust to variation in the frequency and disutility of heart failure hospitalizations. Conclusions and Relevance: In this economic evaluation, based on current cost-effectiveness benchmarks, empagliflozin provides low economic value compared with standard of care for HFpEF, largely due to its lack of efficacy on mortality and small benefit on quality of life.

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

Importance: In the Dapagliflozin and Prevention of Adverse Outcomes in Heart Failure (DAPA-HF) trial, dapagliflozin was shown to reduce cardiovascular mortality and hospitalizations due to heart failure while improving patient-reported health status. However, the cost-effectiveness of adding dapagliflozin therapy to standard of care (SOC) is unknown. Objective: To estimate the cost-effectiveness of dapagliflozin therapy among patients with chronic heart failure with reduced ejection fraction (HFrEF). Design, Setting, and Participants: This Markov cohort cost-effectiveness model used estimates of therapy effectiveness, transition probabilities, and utilities from the DAPA-HF trial and other published literature. Costs were derived from published sources. Patients with HFrEF included subgroups based on diabetes status and health status impairment due to heart failure. We compiled parameters from the literature including DAPA-HF, on which our model is based, and many other sources from December 2019 to February 27, 2021. We performed our analysis in February 2021. Exposures: Dapagliflozin or SOC. Main Outcomes and Measures: Hospitalizations for heart failure, life-years, quality-adjusted life-years (QALYs), costs, and the cost per QALY gained (incremental cost-effectiveness ratio). Results: In the model, dapagliflozin therapy yielded a mean of 0.78 additional life-years and 0.46 additional QALYs compared with SOC at an incremental cost of $38 212, resulting in a cost per QALY gained of $83 650. The cost per QALY was similar for patients with or without diabetes and for patients with mild or moderate impairment of health status due to heart failure. The cost-effectiveness was most sensitive to estimates of the effect on mortality and duration of therapy effectiveness. If the cost of dapagliflozin decreased from $474 to $270 (43% decline), the cost per QALY gained would drop below $50 000. Conclusions and Relevance: These findings suggest that dapagliflozin provides intermediate value compared with SOC, based on American College of Cardiology/American Heart Association benchmarks. Additional data regarding the magnitude of mortality reduction would improve the precision of cost-effectiveness estimates.

County-Level Factors Associated With Cardiovascular Mortality by Race/Ethnicity.

Background Persistent racial/ethnic disparities in cardiovascular disease (CVD) mortality are partially explained by healthcare access and socioeconomic, demographic, and behavioral factors. Little is known about the association between race/ethnicity-specific CVD mortality and county-level factors. Methods and Results Using 2017 county-level data, we studied the association between race/ethnicity-specific CVD age-adjusted mortality rate (AAMR) and county-level factors (demographics, census region, socioeconomics, CVD risk factors, and healthcare access). Univariate and multivariable linear regressions were used to estimate the association between these factors; R2 values were used to assess the factors that accounted for the greatest variation in CVD AAMR by race/ethnicity (non-Hispanic White, non-Hispanic Black, and Hispanic/Latinx individuals). There were 659 740 CVD deaths among non-Hispanic White individuals in 2698 counties; 100 475 deaths among non-Hispanic Black individuals in 717 counties; and 49 493 deaths among Hispanic/Latinx individuals across 267 counties. Non-Hispanic Black individuals had the highest mean CVD AAMR (320.04 deaths per 100 000 individuals), whereas Hispanic/Latinx individuals had the lowest (168.42 deaths per 100 000 individuals). The highest CVD AAMRs across all racial/ethnic groups were observed in the South. In unadjusted analyses, the greatest variation (R2) in CVD AAMR was explained by physical inactivity for non-Hispanic White individuals (32.3%), median household income for non-Hispanic Black individuals (24.7%), and population size for Hispanic/Latinx individuals (28.4%). In multivariable regressions using county-level factor categories, the greatest variation in CVD AAMR was explained by CVD risk factors for non-Hispanic White individuals (35.3%), socioeconomic factors for non-Hispanic Black (25.8%), and demographic factors for Hispanic/Latinx individuals (34.9%). Conclusions The associations between race/ethnicity-specific age-adjusted CVD mortality and county-level factors differ significantly. Interventions to reduce disparities may benefit from being designed accordingly.

Association of Diagnostic Coding-Based Frailty and Outcomes in Patients With Heart Failure: A Report From the Veterans Affairs Health System.

Background The aim of this study was to determine whether frailty is associated with increased admission and mortality risk in the setting of heart failure. Methods and Results This retrospective cohort analysis included patients treated within the Veterans Affairs Health System who had International Classification of Diseases, Ninth Revision (ICD-9) codes for heart failure on 2 or more dates over a 2-year period. The clinical variables identifiable in claims data, such as demographic variables and markers of physical and cognitive dysfunction, were used to identify patients meeting the frailty phenotype. Of 388 785 extracted patients with coding of heart failure between 2015 and 2018, 163 085 patients (41.9%) with ejection fraction (EF) measurement were included in the present analysis (38.3% with reduced EF and 61.7% with preserved EF). There were 16 660 patients (10.2%) who were identified as frail (9.1% in heart failure with reduced EF and 10.9% in heart failure with preserved EF). Frail patients were older, more often depressed, and were likely to have been admitted in the previous year. One-year all-cause mortality rate was 9.7% and 28.1%, and admission rate was 58.1% and 79.5% for nonfrail and frail patients, respectively. Frailty was associated with mortality and admission risk compared with the nonfrail group (adjusted odds ratio [OR], 1.71; 95% CI, 1.65-1.77 for mortality; adjusted OR, 1.29; 95% CI, 1.24-1.34 for admission) independent of EF. Conclusions Frailty based on diagnostic coding was associated with particularly higher risk of mortality despite adjustment for known clinical variables. Our findings underscore the importance of nontraditional parameters in the prognostic assessment.

Trends in Readmission and Mortality Rates Following Heart Failure Hospitalization in the Veterans Affairs Health Care System From 2007 to 2017.

Importance: The Centers for Medicare & Medicaid Services and the Veterans Affairs Health Care System provide incentives for hospitals to reduce 30-day readmission and mortality rates. In contrast with the large body of evidence describing readmission and mortality in the Medicare system, it is unclear how heart failure readmission and mortality rates have changed during this period in the Veterans Affairs Health Care System. Objectives: To evaluate trends in readmission and mortality after heart failure admission in the Veterans Affairs Health Care System, which had no financial penalties, in a decade involving focus on heart failure readmission reduction (2007-2017). Design, Setting, and Participants: This cohort study used data from all Veterans Affairs-paid heart failure admissions from January 2007 to September 2017. All Veterans Affairs-paid hospital admissions to Veterans Affairs and non-Veterans Affairs facilities for a primary diagnosis of heart failure were included, when the admission was paid for by the Veterans Affairs. Data analyses were conducted from October 2018 to March 2020. Exposures: Admission for a primary diagnosis of heart failure at discharge. Main Outcomes and Measures: Thirty-day all-cause readmission and mortality rates. Results: A total of 164 566 patients with 304 374 hospital admissions were included. Among the 304 374 hospital admissions between 2007 and 2017, 298 260 (98.0%) were for male patients, and 195 205 (64.4%) were for white patients. The mean (SD) age was 70.8 (11.5) years. The adjusted odds ratio of 30-day readmission declined throughout the study period to 0.85 (95% CI, 0.83-0.88) in 2015 to 2017 compared with 2007 to 2008. The adjusted odds ratio of 30-day mortality remained stable, with an adjusted odds ratio of 1.01 (95% CI, 0.96-1.06) in 2015 to 2017 compared with 2007 to 2008. Stratification by left ventricular ejection fraction showed similar readmission reduction trends and no significant change in mortality, regardless of strata. Conclusions and Relevance: In this analysis of an integrated health care system that provided guidance and nonfinancial incentives for reducing readmissions, such as public reporting of readmission rates, risk-adjusted 30-day readmission declined despite inclusion of clinical variables in risk adjustment, but mortality did not decline. Future investigations should focus on evaluating the effectiveness of specific approaches to readmission reduction to inform efficient and effective application in individual health systems, hospitals, and practices.

Prognostic Implications of Early and Midrange Readmissions After Acute Heart Failure Hospitalizations: A Report From a Japanese Multicenter Registry.

Background Although 30-day readmission is thought to be an important quality indicator in patients with hospitalized heart failure, its prognostic impact and comparison of patients who were readmitted beyond 30 days has not been investigated. We assessed early (0-30 days) versus midrange (31-90 days) readmission in terms of incidence and distribution, and elucidated whether the timing of readmission could have a different prognostic significance. Methods and Results We examined patients with hospitalized heart failure registered in the WET-HF (West Tokyo Heart Failure) registry. The primary outcomes analyzed were all-cause death and HF readmission. Data of 3592 consecutive patients with hospitalized heart failure (median follow-up, 2.0 years [interquartile range, 0.8-3.1 years]; 39.6% women, mean age 73.9±13.3 years) were analyzed. Within 90 days after discharge, HF readmissions occurred in 11.1% patients. Of them, patients readmitted within 30 and 31 to 90 days after discharge accounted for 43.1% and 56.9%, respectively. Independent predictors of 30- and 90-day readmission were almost identical, and after adjustment, readmission for HF within 90 days (including both early and midrange readmission) was an independent predictor of subsequent all-cause death (hazard ratio, 2.36; P<0.001). Among 90-day readmitted patients, the time interval from discharge to readmission was not significantly associated with subsequent all-cause death. Conclusions Among patients readmitted within 90 days after index hospitalization discharge, ≈60% of readmission events occurred beyond 30 days. Patients readmitted within 90 days had a higher risk of long-term mortality, regardless of the temporal proximity of readmission to the index hospitalization.

A novel therapy for an unusual problem: IL-1 receptor antagonist for recurrent post-transplant pericarditis.

Heart transplant (HTx) recipients are at increased risk of pericardial disease. Idiopathic recurrent pericarditis has not been previously described following HTx. We describe a 35-year-old male who was admitted with pericarditis and moderate pericardial effusion 10 months after HTx. Two weeks before his admission, his prednisone had been tapered off. A thorough infectious workup and endomyocardial biopsy was unrevealing. He was started on colchicine with the addition of tapering prednisone regimen of 40 mg daily due to unresolved pain. Over the next several years, he had three recurrent episodes of pericarditis requiring re-initiation of prednisone with extensive investigations negative for rejection, autoimmune, and infectious causes. Cardiac MRI confirmed pericardial inflammation. Due to his recurrent course and inability to wean off prednisone, anakinra, an IL-1 receptor antagonist, was started at 100 mg sc daily. This allowed successful discontinuation of prednisone. He is now 34 months post-transplant without recurrence on anakinra and colchicine maintenance. Due to the overlap between idiopathic recurrent pericarditis and auto-inflammatory diseases, there is growing evidence for utilizing IL-1 receptor antagonists in this condition. While pericarditis is common in the HTx population, this is the first report of successful use of an IL-1 receptor blocker for pericarditis in this population.