Milton Packer During a median 16 months of treatment, 19.4% of the 1863 patients randomly assigned to take empagliflozin 10 mg/day had a primary endpoint event of death from cardiovascular causes or hospitalization for HF, compared with 24.7% of the 1867 patients taking placebo.

“This decline is expected whenever hospitalizations that are not particularly influenced by a treatment are added in a stepwise manner to the analysis of events in a trial of patients with heart failure and a preserved ejection fraction, in whom only 46% of the hospital admissions are related to a cardiovascular reason and only 18% are related to worsening heart failure,” say Milton Packer (Baylor Heart and Vascular Institute, Dallas, Texas, USA) and study co-authors.

This suggests “that eGFR slope analysis has limitations as a surrogate for predicting the effect of drugs on renal outcomes in patients with heart failure,” write Milton Packer (Baylor University Medical Center, Dallas, Texas, USA) and study co-authors.

These participants’ clinical features and treatment history suggest “a degree of diuretic resistance, a finding supported by the lower values of serum chloride in these patients,” write Milton Packer (Baylor University Medical Center, Dallas, Texas, USA) and co-researchers in the Journal of the American College of Cardiology .

Milton Packer (Baylor University Medical Center, Dallas, Texas, USA) and study co-authors note that their findings are in line with those from DAPA-HF, but based on a larger proportion of study participants taking neprilysin inhibitors and a higher rate of endpoint events.

Milton Packer (Baylor University Medical Center, Dallas, Texas, USA) and study co-authors believe that this may underlie the positive effect of neprilysin inhibition on kidney function, given the “effects of increased renal cGMP on proximal tubular reabsorption of sodium and protein, tubuloglomerular feedback, and renal fibrosis that have been shown in experimental models.”