New Data From the Phase III DAPA-HF Trial Showed FARXIGA Reduced the Worsening of Heart Failure or Cardiovascular Death in HFrEF Patients With and Without Chronic Kidney Disease

AstraZeneca today announced a pre-specified sub-analysis from the landmark Phase III DAPA-HF trial investigating FARXIGA (dapagliflozin) for the treatment of heart failure (HF). The data showed that FARXIGA on top of standard of care reduced the incidence of the primary composite endpoint of cardiovascular (CV) death or worsening of HF in patients with HF with reduced ejection fraction (HFrEF), irrespective of the presence of chronic kidney disease (CKD).

These data were presented today at the American Society of Nephrology (ASN) Kidney Week 2019, which takes place from November 5-10, 2019 in Washington, DC.

Elisabeth Björk, Senior Vice President, Head of Late-stage Development, Cardiovascular, Renal and Metabolism, BioPharmaceuticals R&D, said: “These results underscore our commitment to reduce the burden of cardiovascular, renal and metabolic diseases. Heart failure affects 64 million patients worldwide, and more than 40% of people living with heart failure have chronic kidney disease, considerably worsening their prognoses and reducing their probability of survival. We are proud our research will help support potential solutions for the millions of people impacted by these interrelated diseases.”

DAPA-HF is the first outcomes trial with an SGLT2 inhibitor investigating the treatment of HF in patients with HFrEF with and without type 2 diabetes (T2D). In the sub-analysis, FARXIGA treatment was associated with a 28% relative risk reduction (absolute risk reduction 19.9% vs 26.3%, HR 0.72 [95% CI 0.59-0.86]) for the composite of CV death or worsening HF event in patients with CKD (estimated glomerular filtration rate [eGFR] < 60 ml/min/1.73m² at baseline) and by a similar magnitude in those patients without CKD (13.8% vs 17.6%, HR 0.76 [95% CI 0.63, 0.92]).

The sub-analysis also suggested that FARXIGA may attenuate the long-term decline in glomerular filtration rate (GFR) in patients with HF after the expected initial small reduction in eGFR. The rates of amputation, fracture, volume depletion and renal adverse events were balanced between treatment groups in both the patients with and without CKD.

These data add to the scientific evidence for FARXIGA, which is now approved in the US to reduce the risk of hospitalization for heart failure (hHF) in adults with T2D and established CV disease or multiple CV risk factors, based on results from the landmark Phase III DECLARE-TIMI 58 trial.

DECLARE-TIMI 58 is the largest CV outcomes trial conducted for an SGLT2 inhibitor to date, evaluating T2D patients with multiple CV risk factors or established CV disease. A new sub-analysis from that trial showed that FARXIGA slowed the progression of renal disease across all subgroups of patients with T2D, including patients with normal kidney function and in patients with normo-albuminuria. FARXIGA attenuated the eGFR decline in patients with T2D overall and in subgroups based on baseline eGFR, urine albumin-to-creatinine ratio (UACR), use of ACEi/ARB and diuretics. Although only nominally significant, as endpoints were exploratory, fewer patients experienced an eGFR decline of 30% (HR 0.68 [95% CI 0.58, 0.79], p<0.002), 40% (HR 0.54 [95% CI 0.43, 0.67], p<0.002), or 50% (HR 0.57 [95% CI 0.40, 0.81], p<0.002) to eGFR <60 ml/min/1.73m² with FARXIGA versus placebo.