Neutrophil-to-Lymphocyte Ratio in Patients With Heart Failure: Findings From The EMPEROR Program

Background Sodium–glucose cotransporter 2 inhibitors (SGLT2i) are a cornerstone of treatment for chronic heart failure (CHF), a condition characterised by systemic inflammation and congestion. Objectives We investigated the relationship between the neutrophil-to-lymphocyte ratio (NLR), which is thought to reflect both inflammation and congestion, and the clinical characteristics and outcomes of patients with CHF. Additionally, we sought to evaluate the effects of empagliflozin on NLR and across NLR quintiles. Methods For this post-hoc analysis, we used the EMPEROR-Pooled database, which combines the EMPEROR-Reduced (NCT03057977) and EMPEROR-Preserved (NCT03057951) trials, in which 9706 patients with CHF were randomised to empagliflozin or placebo and had NLR available at baseline. The primary outcome was time to first heart failure hospitalisation or cardiovascular death; secondary endpoints included all-cause mortality and renal outcomes. Results Compared with patients in the lowest NLR quintile, those in the highest quintile were older, more likely to be men, more symptomatic, had higher plasma NT-proBNP and more likely to be treated with loop diuretics. Compared to the lowest NLR quintile, patients in the highest quintile had a greater risk of the primary outcome (14.9% versus 27.3% events; adjusted hazard ratio 1.44 (1.16-1.80); p=0.001), mainly due to more heart failure hospitalisations. Baseline NLR did not modify the effect of empagliflozin on either primary and secondary endpoints. NLR increased during follow-up but this was not affected by empagliflozin. Conclusions In patients with CHF, a higher NLR was associated with greater congestion and poorer prognosis. The efficacy of empagliflozin was consistent, regardless of baseline NLR.