Treatment of severe heart failure (HF) across the spectrum of LVEF with the SGLT2 inihbitor dapagliflozin appeared to be safe and effective in reducing the risk of cardiovascular death or worsening HF, according to an analysis of results from the DAPA-HF and DELIVER clinical trials published March 5 in JACC: Heart Failure.

While SGLT2 inhibitors have consistently shown benefit in decreasing morbidity and mortality among patients with chronic HF across the LVEF spectrum, there remains an unmet need for patients with more severe stages of HF. Riccardo M. Inciardi, MD, PhD, et al., conducted a post hoc pooled participant-level analysis of the placebo-controlled randomized trial DAPA-HF and DELIVER trials to examine the safety and efficacy of dapagliflozin according to HF severity. Severe HF was defined as NYHA functional class III/IV, evidence of HF with reduced, mildly reduced or preserved LVEF, HF hospitalization within the previous 12 months and adverse patient-reported symptom burden (Kansas City Cardiomyopathy Questionnaire-Total Symptoms Score <75).

Of the 10,948 patients in the analysis, 730 (6.7%) met the definition of severe HF; 6.2% with LVEF ≤40%, 9.1% with LVEF 41-49% and 5.6% with LVEF ≥50%.

Results showed that the primary endpoint of cardiovascular death or first worsening HF event by severe HF status occurred in 231 patients, at a rate of 20 per 100-patient years over the median 22 months of follow-up. Furthermore, the rate of primary outcome events was higher among those with than those without severe HF (adjusted hazard ratio, 1.85), regardless of LVEF (Pinteraction, 0.98). The risk of the primary endpoint was consistently reduced with dapagliflozin regardless of severe HF status across the spectrum of LVEF. Similarly, the safety of the drug was consistent regardless of severe HF status.

Patients with severe HF were more likely to be female, White, have a higher BMI and originate from Europe or Saudi Arabia, and had a higher burden of comorbidities including diabetes, atrial fibrillation and chronic kidney disease.

The authors write that in a large global contemporary HF population, these "data support the role of [SGLT2 inhibitors] in patients with more advanced HF stages for whom current treatment options might be limited or not well tolerated."