November 15, 2018 — AstraZeneca announced positive full results from the DECLARE-TIMI 58 cardiovascular (CV) outcomes trial (CVOT) for Farxiga (dapagliflozin) as a late-breaking abstract at the American Heart Association (AHA) Scientific Sessions 2018, Nov. 10-12 in Chicago. Results were simultaneously published in the New England Journal of Medicine (NEJM).1
DECLARE-TIMI 58 is the largest SGLT-2 inhibitor (SGLT-2i) CVOT conducted to date, including more than 17,000 patients across 33 countries. Results showed that Farxiga significantly reduced the risk of hospitalization for heart failure (hHF) or CV death composite vs. placebo by 17 percent (4.9 percent vs. 5.8 percent; HR 0.83 [95 percent CI 0.73-0.95], p=0.005), one of the two primary efficacy endpoints. The reduction in hHF or CV death was consistent across the entire patient population, which included those with CV risk factors and those with established CV disease.1 Farxiga is not indicated to reduce the risk of CV events or hHF.
Additionally, there were fewer major adverse cardiovascular events (MACE) observed with Farxiga for the other primary efficacy endpoint, however this did not reach statistical significance (8.8 percent for Farxiga vs. 9.4 percent for placebo; HR 0.93 [95 percent CI 0.84-1.03], p=0.17).1
DECLARE-TIMI 58 also confirmed the safety profile for Farxiga, which met the primary safety endpoint of non-inferiority vs. placebo, demonstrating no increase in the composite of MACE, defined as CV death, heart attack or stroke.1
On other relevant safety measures, the trial showed no imbalance with Farxiga vs. placebo in amputations (1.4 percent vs. 1.3 percent), fractures (5.3 percent vs. 5.1 percent), bladder cancer (0.3 percent vs. 0.5 percent) or Fournier’s gangrene (1 case vs. 5 cases). The respective incidences of diabetic ketoacidosis (0.3 percent vs. 0.1 percent) and genital infections (0.9 percent vs. 0.1 percent) were rare.1
Although secondary endpoints were only nominally significant, the renal composite endpoint showed that Farxiga reduced the rate of new or worsening nephropathy by 24 percent vs. placebo across the broad patient population studied (4.3 percent vs. 5.6 percent; HR 0.76 [95 percent CI 0.67-0.87]), and there were fewer all-cause mortality events with Farxiga vs. placebo (6.2 percent vs. 6.6 percent; HR 0.93 [95 percent CI 0.82-1.04]).1
Farxiga is not indicated to reduce the risk of HF, other CV outcomes, nephropathy or all-cause mortality.
FDA Clears Dapagliflozin to Reduce Heart Failure Hospitalizations — October 2019 update
For more information: www.nejm.org
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February 09, 2024 
