FDA Expands Dapagliflozin Label to Include Reducing Risk of CV Death in Heart Failure

Just over a year since AstraZeneca announced topline results, the FDA has approved a label expansion to include reducing cardiovascular (CV) death and heart failure–related hospitalizations for dapagliflozin (Farxiga) based on results of the phase 3 DELIVER trial.

A version of this article was originally published on HCPLive®. This version has been lightly edited.

The FDA has approved a label expansion for dapagliflozin (Farxiga) to now indicate the sodium-glucose cotransporter 2 (SGLT2) inhibitor for reducing risk of cardiovascular (CV) death, hospitalization for heart failure (HF), and urgent HF visits in adults with HF, according to an announcement from AstraZeneca.1

Announced on May 9, 2023, the expanded approval is based on the results of the phase 3 DELIVER trial, which was presented at the European Society of Cardiology (ESC) 2022 Congress and shows use of the agent was associated with a relative risk reduction of 18% for the primary end point of CV death or worsening HF.1,2

“Approximately half of heart failure patients die within 5 years of diagnosis, highlighting an urgent unmet need for well-tolerated treatment options that can bring life-saving benefits and reduce the risk of cardiovascular death," said Ruud Dobber, PhD, executive vice president of the BioPharmaceuticals Business Unit at AstraZeneca.1 "The approval of Farxiga in the US not only reinforces AstraZeneca’s commitment to reducing the burden of this complex and life-threatening disease, but will help patients across the full spectrum of heart failure lead healthier lives.”

On May 6, 2020, the HF community celebrated as dapagliflozin became the first SGLT2 inhibitor to be approved for reducing the risk of CV death and hospitalization for HF in patients with HF with reduced ejection fraction, regardless of diabetes status.3 In the subsequent 3 years, multiple phase 3 trials have demonstrated the class’s efficacy in chronic kidney disease (CKD) and HF with mildly reduced or preserved ejection fraction. As a result, the agents' role has transformed and they have become a staple in treatment algorithms for patients who have HF or CKD.

In the pivotal phase 3 DELIVER trial, a cohort of 6263 patients with an ejection fraction above 40% underwent 1:1 randomization to once-daily 10-mg dapagliflozin or placebo. The primary outcome of interest for the trial was a composite of occurrence of worsening HF or CV death, with worsening HF defined as an unplanned hospitalization for HF or an urgent visit for HF.2

During a median (IQR) of 2.3 (1.7-2.8) years of follow-up, a primary outcome event was identified among 16.4% (n = 512) of the dapagliflozin group and 19.5% (n = 610) of the placebo group (HR, 0.82; 95% CI, 0.73-0.92]; P < .001), with investigators noting similar results observed for those with an ejection fraction below 60% compared with the overall population (HR, 0.83; 95% CI, 0.73-0.95; P = .009). When assessing individual components of the primary outcome, a reduction in rate of hospitalization for HF or urgent visit for HF (HR, 0.79; 95% CI, 0.69-0.91) and CV death (HR, 0.88; 95% CI, 0.74-1.05) was observed for the dapagliflozin vs the placebo group.2

Since the original presentation at ESC 2022, multiple analyses of the trial have provided further insight into the effects of use in this patient population, including those from a special session at the Heart Failure Society of America 2022 annual meeting. Among these were a prespecified time-to-benefit analysis, which showed a statistically significant benefit from use for the primary end point was observed in just 13 days.4

Another analysis concluded that more than 75% of Medicare beneficiaries hospitalized with HF at centers within the Get With The Guidelines-Heart Failure Registry would be considered candidates for dapagliflozin use using eligibility criteria from the DELIVER trial.5


1. Farxiga extended in the US to reduce risk of cardiovascular death and hospitalisation for heart failure to a broader range of patients. News release. AstraZeneca. May 9, 2023. Accessed May 9, 2023.

2. Campbell P. Dapagliflozin proves HFPEF benefit in deliver trial. HCPLive. August 27, 2022. Accessed May 9, 2023.

3. Campbell P. Dapagliflozin receives heart failure approval for non-diabetic patients. HCPLive. May 6, 2020. Accessed May 9, 2023.

4. Campbell P. Dapagliflozin’s benefit in HFPEF reaches significance within 2 weeks, study finds. HCPLive. October 3, 2022. Accessed May 9, 2023.

5. Campbell P. 8-in-10 Medicare beneficiaries hospitalized with HFPEF could be considered candidates for dapagliflozin. HCPLive. October 4, 2022. Accessed May 9, 2023.

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