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

Abstract

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.

Figure 1.. Tornado Plot Demonstrating 1-Way Sensitivity Analysis for the Most Relevant Parameters

Parameters were tested across 95% CIs where available or across a reasonable distribution otherwise. CVD indicates cardiovascular death; HFH, heart failure hospitalization; HR, hazard ratio; NCVD, noncardiovascular death; QALY, quality-adjusted life year; and RR, rate ratio.

Figure 2.. Sensitivity Analysis of the Price of Dapagliflozin

The incremental cost-effectiveness ratio is plotted across a broad range of costs of dapagliflozin for the full cohort as well as each of our subgroups. The lower bound of costs of dapagliflozin is the lower limit of our 95% CI, but the upper bound was extended beyond the uninsured cost because our 95% CI did not include the uninsured cost. Vertical lines are plotted at different costs associated with dapagliflozin with the base case (Medicare Part D paid price to pharmacies). A indicates estimated generic cost ($0.17/d); B, Medicare Part D price after mean rebate (28.8%) ($9.99/d); C, Department of Veterans Affairs, Department of Defense, Public Health Service, and the Coast Guard (Big 4) ($11.50/d); D, base case ($15.79/d) and National Average Drug Acquisition Cost ($15.76/d); E, Federal Supply Schedule ($16.00/d); F, list price ($16.41/d); G, wholesale acquisition cost ($16.91/d); H, retail pharmacy price ($20.14/d); I, average wholesale price ($20.29/d); J, uninsured price ($24.18/d); HF, heart failure; and QALY, quality-adjusted life-year.

Figure 3.. Sensitivity Analyses

A, Two-way sensitivity analysis of monthly probability of cardiovascular death (CVD) and hazard ratio (HR) for CVD at different willingness-to-pay thresholds. The monthly probability of CVD and the HR for CVD with dapagliflozin treatment were simultaneously varied across their respective distributions. For each level of monthly probability of CVD, the mean survival in the standard of care arm in years was calculated and plotted as the y-axis. Combinations of monthly probability of CVD and HR for CVD with dapagliflozin treatment that result in incremental cost-effectiveness ratios (ICERs) of less than $50 000, $50 000 to $100 000, greater than $100 000 to $150 000, and greater than $150 000 per quality-adjusted life-year (QALY) gained. The black dot represents the ICER of $75 661 at the base case values of probability of CVD and HR for CVD with dapagliflozin treatment. B, Probabilistic sensitivity analysis of cost-effectiveness acceptability curve in the base case. All model parameters were independently varied across their distributions in a probabilistic sensitivity analysis for 10 000 iterations. We have plotted the percentage of iterations that were cost-effective across willingness-to-pay thresholds.