In-hospital initiation of an SGLT2 inhibitor in an elderly patient with acute heart failure
15 Feb 2024
byDr. Kevin Kam
Presentation and management
A 76-year-old female was hospitalized in July 2023 due to a 3-month history of shortness of breath (SoB), lower limb oedema and reduced exercise tolerance with New York Heart Association (NYHA) functional class II. At the time of hospitalization, she experienced acute pulmonary oedema, which was effectively treated with intravenous furosemide supported by a short course of continuous positive airway pressure (CPAP) ventilation. The patient also had multiple comorbidities on background medications, including hypertension treated with losartan 25 mg daily and amlodipine 10 mg daily, type 2 diabetes mellitus (T2DM) treated with metformin 500 mg BID, atrial fibrillation treated with apixaban 5 mg BID, as well asobesity and obstructive sleep apnoea.
Upon hospital admission, point-of-care ultrasound (POCUS) of heart showed an ejection fraction (EF) of 55–60 percent, and visual assessment suggested moderate concentric left ventricular hypertrophy (LVH) and significant left atrial enlargement (LAE). Right heart function and size were within normal range without evidence of pericardial effusion. Findings were compatible with acute heart failure (HF) with preserved ejection fraction (HFpEF), given the underlying structural heart abnormalities including LVH and LAE. The patient had moderate renal impairment (estimated glomerular filtration rate [eGFR], 45 mL/min/1.73 m2) and proteinuria (urine total protein/creatinine ratio, 450 mg/g) due to diabetic nephropathy. No electrolyte imbalance was observed. Her blood pressure (BP) was 180/110 mm Hg, for which losartan was uptitrated to 50 mg daily. On day 4 of hospitalization, spironolactone 25 mg daily and empagliflozin 10 mg daily were added as guideline-directed medical therapy (GDMT) for HFpEF. 1-3
Having adequate diuresis with intravenous frusemide followed by two days of empagliflozin initiation, the patient became euvolemic with no adverse effects reported. She was then discharged from our hospital and further managed at our Ambulatory Heart Failure Clinic, where formal echocardiography assessment confirmed the diagnosis of HFpEF (LVEF, 60 percent) that was consistent with POCUS findings.
Two weeks after discharge, the patient’s SoB improved, with NYHA functional class I. At 1 month after discharge, her clinical condition continued to improve, with resolution of limb oedema and resumption of usual activities. N-terminal pro B-type natriuretic peptide (NT-proBNP) was substantially reduced to 940 pg/mL, eGFR increased to 50 mL/min/1.73 m2, and proteinuria was down to 340 mg/g. Four months after discharge, her BP normalized (120/80 mm Hg) and body weight was reduced by 2 kg. In October 2023 (ie, 3-month postdischarge), she remained well, and was discharged to our General Cardiology Clinic. As winter approached, the patient was encouraged to receive influenza vaccination to prevent influenza-related decompensation and pneumonia.
Discussion
Patients hospitalized for acute HFare particularly vulnerable in the first 90 days after discharge, during which mortality and readmission rates are increased to nearly 15 percent and 30 percent, respectively.4 Complete decongestion is therefore one of the principal treatment goals as residual congestion at hospital discharge contributes to cardiac decompensation, resulting in rehospitalization and poor prognosis.5
Initiation of GDMT is shown to improve symptoms as well as reduce morbidity and mortality in both acute and chronic HFpEF.3 Sodium-glucose cotransporter 2 (SGLT2) inhibitors, such as empagliflozin and dapaglifozin, are now a part of GDMT for HFpEF recommended by the European Society of Cardiology (ESC; class I recommendation) and the American College of Cardiology (ACC; class 2A recommendation).2,3 The recommendations were based on phase III randomized controlled trials, including EMPEROR-Preserved, which showed a significantly reduced risk of cardiovascular death or HF hospitalization with empagliflozin vs placebo (hazard ratio, 0.79; 95 percent confidence interval [CI], 0.69–0.90; p<0.001) in patients with chronic HFpEF or HF with mildly reduced EF.2,3,6
Furthermore, the ESC and ACC support early initiation of empagliflozin based on studies including EMPULSE, which included 530 patients with acute de novo or decompensated chronic HF.2,3,7 They were randomized in hospital to receive empagliflozin 10 mg daily or placebo for up to 90 days. Results showed that in-hospital initiation of empagliflozin was associated with a statistically significant clinical benefit (ie, a hierarchical composite of death from any cause, number of HF events and time to first HF event, or a ≥5-point difference in change from baseline in the Kansas City Cardiomyopathy Questionnaire Total Symptom Score at 90 days) vs placebo (stratified win ratio, 1.36; 95 percent CI, 1.09–1.68; p=0.0054). (Figure) The beneficial effect was consistent across the spectrum of LVEF, HF status (acute de novo or decompensated chronic HF), and presence or absence of diabetes. Empagliflozin was also associated with a greater NTproBNP reduction at day 30 (adjusted geometric mean ratio, 0.90; 95 percent CI, 0.82–0.98) vs placebo.7
In two analyses of EMPULSE, empagliflozin demonstrated significantly greater reductions in all studied markers of decongestion at all time points at days 15, 30 and 90 (all p<0.05), indicating that in-hospital initiation of empagliflozin provides early, effective and sustained decongestion.5 Although empagliflozin caused an initial dip in eGFR (-2 mL/min/1.73 m2 at day 15 vs placebo), the eGFR was similar between empagliflozin and placebo at day 90. Importantly, the overall clinical benefit of empagliflozin was unaffected by baseline eGFR.8 As shown in our patient’s case, early decongestion was achieved, and renal function improved after in-hospital initiation of empagliflozin.
Empagliflozin is well tolerated. When initiated during HF hospitalization, empagliflozin was associated with fewer serious adverse events vs placebo (32.3 percent vs 43.6 percent), and no ketoacidosis events were reported. The most common side effects were urinary tract infections and female genital mycotic infections.7
In light of the proven clinical benefit, in-hospital initiation of empagliflozin is warranted and should be considered in all individuals with HFpEF unless contraindicated. Empagliflozin should be initiated once patients become clinically stable.2
In the absence of echocardiography, POCUS may help identify HF phenotype.9 Notably, empagliflozin’s HFpEF indication has been enlisted in the Hospital Authority’s Drug Formulary since October 2023, making it the only SGLT2 inhibitor indicated across HF phenotypes (with or without T2DM).1,10 In our patient, in-hospital initiation of empagliflozin was well tolerated and optimized clinical outcome, providing improvements in symptoms and functional capacity. Importantly, our patient remained free of rehospitalization for ≥3 months from discharge.
