LAUSR

It can be argued that we live in the golden age of heart failure (HF) therapeutics. The recent development of sodium–glucose co-transporter 2 (SLGT2) inhibitors has now established them as the fourth pillar of guideline-directed medical therapy (GDMT) for patients with HF with reduced ejection fraction (HFrEF) in addition to beta-blockers, angiotensin-converting enzyme inhibitors/ angiotensin receptor blockers/angiotensin receptor–neprilysin inhibitors and mineralocorticoid receptor antagonists. Advances have also been noted in medical therapy for patients with HF with preserved ejection fraction (HFpEF), although the magnitude of the effect of medical therapy in these patients is less pronounced. Despite these advances in the management of chronic HF, the management of acute HF remains largely unchanged. Decongestion with oral or intravenous diuretics is the mainstay of acute HF management. However, development of worsening renal function (WRF) during the management of acute HF can be a major barrier to adequate decongestion and is associated with adverse outcomes.1 In this issue of the Journal, Emmens et al.2 analyzed patients with acute HF who were enrolled in the PROTECT and RELAX-AHF-2 trials to assess the relationship between WRF and outcomes, based on the response to diuretic therapy. PROTECT was a randomized, placebo-controlled trial of rolofylline, administered within 24 h of admission and for up to 3 days, in patients with acute HF and creatinine clearance of 20–80 ml/min.3 RELAX-AHF-2 was a randomized, placebo-controlled trial of intravenous serelaxin, administered within 16 h of admission and up to 48 h, in patients with acute HF and mild–moderate renal dysfunction (estimated glomerular filtration rate [eGFR] 25–75 ml/min/1.73 m2).4 A total of 1698 out of 2033 patients enrolled in PROTECT (median left ventricular ejection fraction [LVEF] 30%, median eGFR 46 ml/min/1.73 m2) and a total of 5586 out of 6545 patients enrolled in RELAX-AHF-2 (median LVEF 38%, median eGFR 50 ml/min/1.73 m2), who had creatinine measurements at baseline and 4 days, were included