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


Announced just more than a year after AstraZeneca announced topline results, the FDA has approved a label expansion to include reducing cardiovascular death and HF hospitalizations for dapagliflozin based on results of the phase 3 DELIVER trial.

US Food and Drug Administration Logo in black over a white background | Credit: US Food and Drug Administration Logo

Credit: US Food and Drug Administration

The US Food and Drug Administration has approved a label expansion for dapagliflozin (Farxiga), which now indicates the SGLT2 inhibitor for reducing risk of cardiovascular death, hospitalization for heart failure, and urgent heart failure visits in adults with heart failure, according to an announcement from AstraZeneca.1

Announced on May 9, 2023, the agent’s 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 found use of the agent was associated with a relative risk reduction of 18% for the primary endpoint of cardiovascular death or worsening heart failure.1,2

“Approximately half of heart failure patients die within five 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, 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 heart failure community celebrated as dapagliflozin became the first SGLT2 inhibitor to be approved for reducing the risk of cardiovascular death and hospitalization for heart failure in patients with heart failure with reduced ejection fraction (HFrEF), regardless of diabetes status.3 In the subsequent 3 years, multiple phase 3 trials have demonstrated the class’s efficacy in CKD and heart failure with mildly reduced or preserved ejection fraction. As a result, the agents role transformed and have become a staple in treatment algorithms for heart failure and chronic kidney disease (CKD) patients.

In the pivotal phase 3 DELIVER trial, a cohort of 6263 patients with an ejection fraction greater than 40% underwent randomization in1:1 ratio to once daily 10 mg dapagliflozin or placebo therapy. The primary outcome of interest for the trial was a composite of occurrence of worsening heart failure or cardiovascular death, with worsening heart failure defined as an unplanned hospitalization for heart failure or an urgent visit for heart failure.2

During a median of 2.3 (IQR, 1.7-2.8) years of follow-up, a primary outcome event was identified among 16.4% (n=512) of the dapagliflozin group and among 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 of less than 60% compared to those of 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 heart failure or urgent visit for heart failure (HR, 0.79 [95% CI, 0.69-0.91]) and cardiovascular death (HR, 0.88 [95% CI, 0.74-1.05]) was observed for the dapagliflozin group compared to the placebo group.2

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

Another analysis concluded more than 75% of Medicare beneficiaries hospitalized with heart failure at centers within the Get With The Guidelines-Heart Failure (GWTG-HF) Registry would be considered candidates for dapagliflozin use using eligibility criteria from the DELIVER trial.5 For more insight on this analysis, check out the video below with Stephen Greene, MD, assistant professor of medicine at Duke University School of Medicine:


  1. Farxiga extended in the US to reduce risk of cardiovascular death and hospitalisation for heart failure to a broader range of patients. AstraZeneca. May 9, 2023. Accessed May 9, 2023. https://www.astrazeneca.com/media-centre/press-releases/2023/farxiga-extended-in-the-us-for-heart-failure.html.
  2. Campbell P. Dapagliflozin proves HFPEF benefit in deliver trial. HCP Live. August 27, 2022. Accessed May 9, 2023. https://www.hcplive.com/view/dapagliflozin-proves-hfpef-benefit-in-deliver-trial.
  3. Campbell P. Dapagliflozin receives heart failure approval for non-diabetic patients. HCP Live. May 6, 2020. Accessed May 9, 2023. https://www.hcplive.com/view/farxiga-dapagliflozin-heart-failure-approval-for-nondiabetic-patients.
  4. Campbell P. Dapagliflozin’s benefit in HFPEF reaches significance within 2 weeks, study finds. HCP Live. October 3, 2022. Accessed May 9, 2023. https://www.hcplive.com/view/dapagliflozin-benefit-in-hfpef-reaches-significance-within-2-weeks-study-finds.
  5. Campbell P. 8-in-10 Medicare beneficiaries hospitalized with HFPEF could be considered candidates for Dapagliflozin. HCP Live. October 4, 2022. Accessed May 9, 2023. https://www.hcplive.com/view/8-in-10-medicare-beneficiares-hospitalized-with-hfpef-considered-candidates-for-dapagliflozin.
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