BARCELONA, Spain – AstraZeneca’s SGLT-2 inhibitor Forxiga (ingredient: dapagliflozin) proved its effectiveness in reducing cardiovascular death or heart failure (HF) in patients with a mildly reduced or preserved ejection fraction (EFmrEF or HFpEF) in phase 3 DELIVER study.
Forxiga created new clinical evidence for patients with HF with improved ejection fraction (HFimpEF) with EF of more than 40 percent, becoming a treatment usable for the most extensive HF patients among existing SGLT-2 inhibitors.
Dr. Scott D. Solomon of Brigham and Women’s Hospital at Harvard Medical School released phase 3 DELIVER study results at the European Society of Cardiology Congress 2022 (ESC 2022) in Barcelona, Spain, on Saturday.
Forxiga beneficial for all HF patients regardless of EF, treatment environment
DELIVER is a phase-3, randomized, controlled trial conducted among patients with HFmrEF (heart failure with midrange ejection fraction) and HFpEF (heart failure with preserved ejection fraction). The trial drew attention because it included the broadest patient group among SGLT-2 inhibitor studies.
The study on 6,263 patients included treatment environments in real clinical settings, including patients with recent hospitalization and those with HFimpEF.
The study results showed that Forxiga reduced the combined risk of cardiovascular death or worsening heart failure (hospitalization or urgent visit for HF) regardless of EF or patients’ treatment environments (inpatients or outpatients).
It also lowered total HF events and cardiovascular deaths and improved symptom burden.
The hazard ratio of the Forxiga-treated group, with the primary outcome set as a composite of cardiovascular death and worsening HF, was 0.82, an 18 percent improvement compared to the placebo group. In addition, Forxiga’s benefits were consistent in sub-analysis by EF rate, hospitalization history, and HFrEF history.
“Dapagliflozin was also effective in patients with HFimpEF, which used to be excluded from all the other previous studies,” Solomon said. “These data provide strong evidence to support the use of an SGLT-2 as a foundational therapy in most HF patients, with or without type-2 diabetes or EF.”
Forxiga improves treatment access for HF patients
In the second presentation, Pardeep Jhund of the University of Glasgow from the U.K. provided the results of two Forxiga trials, DELIVER and DAPA-HF, analyzing the drug’s efficacy across the full EF range.
“The current guidelines recommend dapagliflozin only for patients with HFrEF with an EF of 40 percent or less,” Jhund said. “But in real clinical settings, the largest 55 percent of HF patients are those with HFmrEF and HFpEF with EF of 40 percent or more. Unfortunately, despite a poor prognosis, these patients have almost no treatment option.”
He added that empagliflozin might not benefit HF patients with high EF in the same class as dapagliflozin.
The integration of data from the DAPA-HF study on HFrEF patients and DELIVER on HFmrEF and HFpEF patients showed that the trials included 11,007 patients with left ventricular EF (LVEF), ranging from 2 percent to 88 percent. The median EF was 44 percent, and the median follow-up was 22 months.
The analysis showed that Forxiga significantly improved all outcomes, including cardiovascular death, all-cause death, major cardiovascular events, first HF hospitalization, and cardiovascular death/first HF hospitalization.
“Patients often have to wait for heart scans to measure EF and decide on treatment options. So, we can prescribe dapagliflozin before EF measurement to increase patients’ treatment access, as long as there is no contraindication,” Jhund said.
‘We should use SGLT-2 inhibitor first for all HF patients'
Dr. Muthiah Vaduganathan of Brigham and Women’s Hospital at Harvard Medical School gave the last presentation.
He presented the meta-analysis of phase 3 trials of SGLT-2 inhibitors, evaluating the class effect.
His outcomes were two kinds.
The first was a meta-analysis of the DELIVER and EMPEROR-Preserved studies on HFmrEF and HFpEF patients.
These phase 3 studies included 12,251 patients.
The results showed that SGLT-2 inhibitors (Forxiga and Jardiance) reduced the risk of cardiovascular death and first hospitalization for HF by 20 percent, compared with the placebo.
The second was the results of a meta-analysis on five phase 3 randomized, controlled trials related to HF. These studies involved SGLT-2 inhibitors in more than 1,000 HF patients.
The five studies were DAPA-HF and EMPEROR-Reduced in HFrEF patients, DELIVER, EMPEROR-Preserved, and SOLOIST-WHF in HFmrEF and HFpEF patients.
SOLOIST-WHF compared sotagliflozin with placebo in 1,222 patients with type 2 diabetes who were recently hospitalized for worsening HF.
The inclusive meta-analysis of more than 20,000 HF patients showed that SGLT-2 inhibitors extended the survival of patients, reduced cardiovascular events and symptom burden, and improved overall health conditions.