The widespread use of dapagliflozin for treating heart failure (HF) with reduced ejection fraction (HFrEF) has the potential to improve long-term clinical outcomes and may be a cost-effective treatment, according the a recent study published in JAMA Network Open.1 In a simulation model, researchers found that adding dapagliflozin to guideline-directed medical therapy (GDMT) has the potential to produce substantial clinical gains in this patient population with an acceptable increase in associated costs.

This study found that at a willingness-to-pay threshold of $100 000 per quality-adjusted life-year (QALY) gained, treatment with dapagliflozin would be a cost-effective therapy regardless of diabetes status. “We have had a slew of new cardiovascular medications enter the market at exorbitant prices, medications that are effective but not cost-effective. In this context, the entry of SGLT2 (sodium glucose cotransporter-2) inhibitors like dapagliflozin at discounted prices, as is usually the case with diabetes medications, is a breath of fresh air,” said study corresponding author Dhruv S. Kazi, MD, associate director of the cardiac critical care unit at Beth Israel Deaconess Medical Center, and associate professor of medicine at Harvard Medical School, in Boston, Massachusetts.

HFrEF is associated with high morbidity, mortality, and health care costs.2 Dapagliflozin is the first SGTLT2 to be approved for treating these patients. The researchers conducted an economic evaluation using participants from the Dapagliflozin in Patients with Heart Failure and Reduced Ejection Fraction (DAPA-HF trial; Identifier: NCT03036124). This phase 3, placebo-controlled, double-masked, randomized trial in patients with HFrEF who had New York Heart Association class II, III, or IV symptoms and a left ventricular ejection fraction of ≤40%. The trial excluded patients with an estimated glomerular filtration rate less than 30 mL/min/1.73 m2 of body surface.

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The team employed a Markov cohort model comparing dapagliflozin and GDMT with guideline-directed medical therapy alone in a hypothetical cohort of adults with similar clinical characteristics. “This is a systematic economic evaluation using a range of data sources including clinical trials, registries, publications, census and survey data, and regulatory documents,” said Dr Kazi. “This was performed completely independent of the commercial sponsor of the drug trials. So, this is an unbiased estimate of cost-effectiveness based on best-available information. Thus, clinicians and payers can take these findings at face value”.

In this simulation, the cost of dapagliflozin was pegged at $4,192 annually and nonparametric modeling was used to estimate long-term survival. The simulated cohort at baseline had a starting median age of 66 years, and 41.8% had diabetes. The researchers found that dapagliflozin has the potential 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).

The authors note that the study has several limitations, including the fact that only one single randomized trial with a mean follow-up of 18 months was used to determine the safety and efficacy of dapagliflozin.

Effects on Healthcare Policy

With this current simulation, adding dapagliflozin to GDMT in patients with HFrEF was projected to lower the rate of HFrEF hospitalizations from 0.10 (95% CI, 0.09-0.11) to 0.07 (95% CI, 0.06-0.08) per person-year. It was also projected that it could improve quality-adjusted survival by 0.63 (95% uncertainty interval [UI], 0.25-0.94).

Patients receiving dapagliflozin incurred $27 700 (95% UI, $25 700-$29 800) in lifetime spending on dapagliflozin, which was only partially offset by savings resulting from reduced HFrEF hospitalizations. After accounting for increased health care costs related to prolonged survival, the intervention arm had a net increase in lifetime health care costs of $42 800 (95% UI, $37 100-$50 300). As a result, adding dapagliflozin to GDMT had an ICER of $68 300 per QALY gained (95% UI, $54 600-$117 600 per QALY gained) compared with GDMT alone, and was cost-effective in 94% of 10 000 probabilistic simulations.

“It is important for clinicians to remember that out-of-pocket costs can vary substantially among patients and from month-to-month for a given patient. A drug may be cost-effective but unaffordable if the patient cannot bear the out-of-pocket costs. We have seen this with cardiovascular drugs in the past,” Dr Kazi said. “As a result, clinicians should have regular conversations with their patients regarding out-of-pocket costs in order to identify and preempt cost-related non-adherence. This effective and cost-effective therapy only works if patients actually take their medications”.

Mikhail Kosiborod, MD, director of cardiometabolic research and co-director of the Saint Luke’s Michael & Marlys Haverty Cardiometabolic Center of Excellence and professor of medicine at the University of Missouri Kansas City said this study demonstrates is that dapagliflozin is not only clinically effective, but also cost-effective based on the current US-based acquisition costs, making it a good investment for the healthcare system. “This further highlights the need to focus on optimal implementation of guideline-directed therapies, including SGLT2 inhibitors such as dapagliflozin, into clinical practice as quickly as efficiently as possible, so that more individuals with heart failure can benefit by living longer, staying out of the hospital and feeling better,” Dr Kosiborod indicated.

This current study is the first systematic cost-effectiveness analysis of dapagliflozin for patients with HFrEF in the United States. Similar analyses in the United Kingdom, Germany, Spain Australia and China also projected dapagliflozin to be cost-effective in those healthcare systems. The authors write that “scalable strategies to ensure affordable access to and widespread uptake of dapagliflozin are urgently needed.”  They note that diabetes therapies, such asSGLT2 inhibitors, receive some of the largest manufacturer discounts in the US pharmaceutical system, and now there are efforts underway that would force payers to pass on at least some of the manufacturer discounts to the patients.

Naveed Amjid Sattar, FMedSci, professor of metabolic medicine at the Institute of Cardiovascular & Medical Sciences at the University of Glasgow, Scotland said this type of study is important because these costs can now be compared to the costs of newer drugs as the armamentarium grows. “The other thing this paper nicely highlights is how much more dapagliflozin is cost-effective in other countries where the drug costs are appreciably lower, in some cases around 10-fold lower,” Dr Sattar said. “Of course, dapagliflozin is soon to become off patent and so costs should decline markedly then.”


  1. Isaza N, Calvachi P, Raber I, et al. Cost-effectiveness of dapagliflozin for the treatment of heart failure with reduced ejection fraction. JAMA Netw Open. 2021;4(7):e2114501.
  2. Urbich M, Globe G, Pantiri K, et al. A systematic review of medical costs associated with heart failure in the USA (2014–2020). PharmacoEconomics. 2020;38(11):1219-1236.

This article originally appeared on The Cardiology Advisor