AstraZeneca’s heart failure drug first to show all-inclusive mortality benefit

Pharma News: In an increasingly competitive heart failure (HF) market, AstraZeneca’s latest data, which was presented at the European Society of Cardiology (ESC) congress 26-29 August 2022, made an impression as it demonstrated the benefits of its sodium-glucose cotransporter 2 (SGLT2) inhibitor, Forxiga (dapagliflozin), for patients with heart failure irrespective of ejection fraction.

In Australia, Forxiga is PBS listed for the treatment of type 2 diabetes mellitus and in December 2021 its listing was extended to treat symptomatic heart failure with reduced ejection fraction (HFrEF). Forxiga is the third SGLT2 inhibitor approved for HF. The others are Novartis’ Entresto (sacubitril-valsartan) and Eli Lilly and Boehringer Ingelheim’s Jardiance (empagliflozin).

At the ESC Congress, Professor Pardeep Jhund from the University of Glasgow in the UK, presented a pooled analysis from the Phase III DAPA-HF and DELIVER trials.

Across the 11,007 patients in the two trials and with median follow up of 1.8 years, the drug reduced the risk of CV death by 14% (p=0.01, absolute risk reduction [ARR] 1.5%) over the median follow-up of 22 months, death from any cause by 10% (p=0.03,), total hospitalisation for HF (hHF) by 29% (p < 0.001), and the composite of death from CV causes, myocardial infarction, or stroke by 10% (p=0.045), in patients with HF irrespective of ejection fraction.

Prof. Jhund remarked “Our findings confirm that all patients with HF, regardless of ejection fraction, may benefit from dapagliflozin in addition to any other HF therapy they are receiving.”

Delving further into the class effects of SGLT2 inhibitors in HF patients with mildly reduced and preserved ejection fraction, Dr Muthiah Vaduganathan from Brigham And Women’s Hospital, Harvard Medical School in Boston USA, presented a prespecified meta-analysis of participant-level data from DELIVER (Farxiga) and from EMPEROR-Preserved (Jardiance) clinical trials.

When the data were pooled (n=12,251), the SGLT2 inhibitors were shown to reduce the risk of the primary outcome of CV death or first hospitalisation for HF by 20% (p<0.001). Substantial reductions in HF hospitalisations were observed (HR 0.74), with more modest reductions in CV death (HR 0.88).

SGLT2 inhibitors reduced total HF hospitalisations by 27%, urgent HF visits by 35% and all-cause hospitalisations by 7%, but with no significant effect on all-cause death. Treatment effects were consistent across all 12 subgroups including patients at the highest end of the ejection fraction spectrum and those already treated with other HF medicines.

Dr. Vaduganathan concluded “This meta-analysis summarises the totality of evidence on SGLT2 inhibitors in HF with an LVEF above 40% and supports their use as foundational therapy in this population.”