Analysis of phase III DECLARE-TIMI 58 trial showed that Farxiga reduced the risk of adverse CV events

Positive results from a pre-specified sub-analysis of the Phase III DECLARE-TIMI 58 trial showed that Farxiga (dapagliflozin) from AstraZeneca, reduced the relative risk of major adverse cardiovascular events (MACE) by 16% compared to placebo in patients with type-2 diabetes (T2D) who had a prior heart attack (myocardial infarction).

In another pre-specified sub-analysis, Farxiga compared to placebo reduced the relative risk of hospitalisation for heart failure (hHF) in patients with T2D regardless of their ejection fraction (EF) status, a measurement of the percentage of blood leaving the heart with each contraction. The data were presented at the American College of Cardiology’s (ACC) 68th Annual Scientific Session, New Orleans, USA and were published in Circulation.

These pre-specified sub-analyses of DECLARE-TIMI 58 add to the positive primary results of the trial presented in November 2018, which showed that Farxiga significantly reduced the risk of the composite of hHF or CV death compared to placebo, consistently across the trial’s entire patient population. Additionally, there were fewer major adverse cardiovascular events observed with Farxiga in the broad patient population, however this did not reach statistical significance.

About DECLARE-TIMI 58 : DECLARE (Dapagliflozin Effect on Cardiovascular Events)-TIMI 58 is an AstraZeneca-sponsored, randomised, double-blinded, placebo-controlled, multicentre trial designed to evaluate the effect of Farxiga compared with placebo on CV outcomes in adults with T2D at risk of CV events, including patients with multiple CV risk factors or established CV disease. DECLARE included more than 17,000 patients across 882 sites in 33 countries and was independently run in collaboration with academic investigators from the TIMI study group (Boston, USA) and the Hadassah Hebrew University Medical Center (Jerusalem, Israel).

About DapaCare : DECLARE is part of the extensive DapaCare clinical programme for Farxiga, which will enrol patients in randomised clinical trials including a wide range of mechanistic trials and is supported by a multinational real-world evidence study (CVD-REAL). The DapaCare clinical programme will generate data across a spectrum of people with CV risk factors, established CV disease and varying stages of renal disease, both with and without T2D. DECLARE is paving the way for three Phase III trials: Dapa-HF, DELIVER and Dapa-CKD. Farxiga is not indicated to reduce the risk of CV events, CV death, or hHF, or the treatment of CKD.

Comment: AstraZeneca had reported that Farxiga met one of two primary endpoints in DECLARE TIMI-58, reducing the risk of cardiovascular death or hospitalization for heart failure, but the drug did not significantly reduce the risk of major adverse cardiovascular events, or MACE, compared to placebo. This sub-analysis expanded on that result, showing Farxiga's benefit to be greater in those with reduced left ventricular ejection fraction, defined in the study as less than 45%. All patients experienced a reduced risk of hospitalization for heart failure. But in those with lower ejection fraction, the risk reduction extended to cardiovascular death and all-cause mortality as well. Also among patients who had a previous heart attack, Farxiga reduced the risk of MACE by 16% compared to placebo.