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

Abstract

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.

Figure 1.. Cost-effectiveness Based on the Monthly Price of Empagliflozin

The incremental cost-effectiveness ratio is plotted across a broad range of price points for empagliflozin in 2021 dollars. Scenarios with and without treatment effect on cardiovascular mortality are shown. Light shaded and darker shaded regions indicate intermediate and high value of treatment, respectively. Vertical lines are plotted at different monthly costs associated with empagliflozin: A, Medicaid price of $121.86; B, VA price of $195.69; C, base case of $326.69; D, Medicare Part D price of $375.24 after mean rebate (26.5%); E, wholesale acquisition cost of $548.54; F, retail pharmacy price of $644.50. CV indicates cardiovascular; QALY, quality-adjusted life-year; VA, Department of Veterans Affairs; WTP, willingness to pay.

Figure 2.. Tornado Plot Demonstrating 1-Way Sensitivity Analyses for Relevant Parameters

The 1-way sensitivity analyses were performed for scenarios with and without treatment effect on cardiovascular mortality. Parameters were tested across 95% CIs where available or across reasonable uncertainty intervals otherwise. CVD indicates cardiovascular death; HFH, heart failure hospitalization; HR, hazard ratio; NCVD, noncardiovascular death; RR, rate ratio; QALY, quality-adjusted life-year.

Figure 3.. Select 2-Way Sensitivity Analyses

The 2-way sensitivity analyses were performed for scenarios with and without treatment effect on cardiovascular mortality. Light shaded and darker shaded regions indicate intermediate and high value of treatment, respectively. A and B, Incremental utility (KCCQ change) and monthly cost of empagliflozin are simultaneously varied. The base case quality-of-life benefit of empagliflozin, as well as higher estimates from other trials of sodium-glucose cotransporter-2 inhibitors, are shown as vertical lines. C and D, Monthly rate and duration of disutility of hospitalization for heart failure are simultaneously varied. The base case rate of hospitalization for heart failure is shown as a vertical line. Duration of disutility may also be interpreted as severity of quality-of-life impairment (eg, 2 months of disutility equivalent to 1 month of disutility twice as severe as the base case estimate). CV indicates cardiovascular; HFH, heart failure hospitalization; ICER, incremental cost-effectiveness ratio; KCCQ, Kansas City Cardiomyopathy Questionnaire; RR, rate ratio; QALY, quality-adjusted life-year.