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

Abstract

Importance: Heart failure with reduced ejection fraction produces substantial morbidity, mortality, and health care costs. Dapagliflozin is the first sodium-glucose cotransporter 2 inhibitor approved for the treatment of heart failure with reduced ejection fraction.

Objective: To examine the cost-effectiveness of adding dapagliflozin to guideline-directed medical therapy for heart failure with reduced ejection fraction in patients with or without diabetes.

Design, setting, and participants: This economic evaluation developed and used a Markov cohort model that compared dapagliflozin and guideline-directed medical therapy with guideline-directed medical therapy alone in a hypothetical cohort of US adults with similar clinical characteristics as participants of the Dapagliflozin in Patients with Heart Failure and Reduced Ejection Fraction (DAPA-HF) trial. Dapagliflozin was assumed to cost $4192 annually. Nonparametric modeling was used to estimate long-term survival. Deterministic and probabilistic sensitivity analyses examined the impact of parameter uncertainty. Data were analyzed between September 2019 and January 2021.

Main outcomes and measures: Lifetime incremental cost-effectiveness ratio in 2020 US dollars per quality-adjusted life-year (QALY) gained.

Results: The simulated cohort had a starting age of 66 years, and 41.8% had diabetes at baseline. Median (interquartile range) survival in the guideline-directed medical therapy arm was 6.8 (3.5-11.3) years. Dapagliflozin was projected to add 0.63 (95% uncertainty interval [UI], 0.25-1.15) QALYs at an incremental lifetime cost of $42 800 (95% UI, $37 100-$50 300), for an incremental cost-effectiveness ratio of $68 300 per QALY gained (95% UI, $54 600-$117 600 per QALY gained; cost-effective in 94% of probabilistic simulations at a threshold of $100 000 per QALY gained). Findings were similar in individuals with or without diabetes but were sensitive to drug cost.

Conclusions and relevance: In this study, adding dapagliflozin to guideline-directed medical therapy was projected to improve long-term clinical outcomes in patients with heart failure with reduced ejection fraction and be cost-effective at current US prices. Scalable strategies for improving uptake of dapagliflozin may improve long-term outcomes in patients with heart failure with reduced ejection fraction.

Figure 1.. Model Structure

The Markov cohort model used in this study simulated a hypothetical cohort of patients with heart failure with reduced ejection fraction (HFrEF) with clinical characteristics similar to the participants of the Dapagliflozin in Patients with Heart Failure and Reduced Ejection Fraction trial. The model compared guideline-directed medical therapy (GDMT) in the control arm with dapagliflozin added to GDMT in the intervention arm. In monthly cycles, patients could continue to live with HF, experience an urgent HF visit, experience a HF hospitalization (with or without a readmission in the first 30 days after the index hospitalization), develop incident diabetes, or die from any cause.

Figure 2.. Sensitivity Analyses

In panel A, the blue dashed line indicates the assumed cost-effectiveness threshold of $100 000 per quality-adjusted life years (QALYs) gained (blue dashed line). Adding dapagliflozin to GDMT was cost-effective in 94% of 10 000 probabilistic simulations.

Figure 3.. Incremental Cost-effectiveness of Dapagliflozin in Treatment of Heart Failure With Reduced Ejection Fraction

We varied the annual cost of dapagliflozin, holding all other input parameters at their base-case value. The different annual costs analyzed included: (1) Federal Supply Schedule (base case, $4192); (2) wholesale acquisition price ($6188); (3) the price obtained if the wholesale acquisition were discounted by 40% (average value of rebates and discounts on diabetes pharmaceuticals) ($3713); and (4) a heavily discounted net price at which dapagliflozin is available in some US markets ($953). The color quadrants indicate the annual cost at which adding dapagliflozin to guideline-directed medical therapy would be cost-effective relative to guideline-directed medical therapy alone at thresholds of $50 000, $100 000, and $150 000 per quality-adjusted life year (QALY) gained. These results permit health systems and clinicians to estimate the incremental cost-effectiveness of dapagliflozin for HFrEF in the context of their cost of a year’s supply of dapagliflozin.