Should empagliflozin be started in a hemodynamically stable, symptomatic post‑CABG patient with an ejection fraction of 49% (heart failure with mildly reduced ejection fraction) and no diabetes?

Empagliflozin Should Be Started Immediately in This Patient

Empagliflozin 10 mg once daily should be initiated now in this hemodynamically stable post-CABG patient with symptomatic heart failure and an ejection fraction of 49%, regardless of the absence of diabetes. 1, 2

Guideline-Based Recommendation

The 2022 ACC/AHA/HFSA guidelines provide a Class 2a, Level B-R recommendation for SGLT2 inhibitors in patients with heart failure with mildly reduced ejection fraction (HFmrEF, LVEF 41-49%) to decrease hospitalizations and cardiovascular mortality, with particular benefit in patients with LVEF on the lower end of this spectrum. 1, 3

• Empagliflozin is specifically recommended for all symptomatic chronic heart failure patients regardless of ejection fraction or diabetes status. 2, 3
• The benefit in EMPEROR-Preserved was consistent across LVEF subgroups, though there was a signal for greater benefit at lower ejection fractions (closer to 50%). 1

Evidence Supporting Use in This Clinical Scenario

Efficacy in Non-Diabetic Patients with HFmrEF

• Empagliflozin reduced cardiovascular death or heart failure hospitalization by 21% (HR 0.79,95% CI 0.69-0.90; P<0.001) in EMPEROR-Preserved, which enrolled patients with LVEF >40%. 1, 4
• The benefit was identical in patients without diabetes (HR 0.78,95% CI 0.64-0.95) compared to those with diabetes (HR 0.79,95% CI 0.67-0.94), with no interaction by diabetes status (P-interaction=0.92). 4
• This 21% reduction was driven primarily by a 29% reduction in heart failure hospitalizations (HR 0.71,95% CI 0.60-0.83). 1

Additional Benefits Relevant to Post-CABG Patients

• Empagliflozin significantly slowed the decline in estimated glomerular filtration rate, providing renal protection that is particularly important in post-surgical patients. 1, 4
• Quality of life improved modestly at 52 weeks, addressing the symptomatic burden in this patient. 1
• Empagliflozin reduced left ventricular end-systolic and end-diastolic volumes, suggesting favorable reverse remodeling that may be particularly beneficial post-revascularization. 5

Clinical Implementation Algorithm

Initiation Criteria (All Met in This Patient)

1. Symptomatic heart failure (patient is symptomatic) 1, 2
2. LVEF 41-49% (patient has EF 49%) 1, 3
3. Hemodynamically stable (no increase in IV diuretics for ≥6 hours, no IV vasodilators or inotropes for ≥24 hours) 3, 6
4. eGFR ≥20 mL/min/1.73m² (verify renal function) 2, 6

Dosing

• Start empagliflozin 10 mg once daily 2, 3, 7
• No dose titration is required, unlike other heart failure medications 3, 6
• Continue all existing guideline-directed medical therapy (ACE inhibitors/ARBs/ARNI, beta-blockers, mineralocorticoid receptor antagonists) 3, 6

Timing

• Initiate during hospitalization or at first post-discharge visit once hemodynamically stable 3, 6
• Do not defer initiation, as delaying treatment results in many eligible patients never receiving the medication within one year 3, 6
• Benefits occur within weeks of initiation, with empagliflozin showing a 58% relative risk reduction as early as 12 days after starting therapy 3, 6

Safety Monitoring

Expected and Manageable Effects

• Monitor for symptomatic hypotension (occurred in only 5.7% vs 5.5% with placebo in EMPEROR-Reduced), particularly in elderly patients or those on high-dose diuretics 2, 6
• Expect a mild, transient decrease in eGFR after initiation—this does not indicate kidney injury and should not prompt discontinuation 2, 6
• Watch for genital mycotic infections (1.5-1.7%) and urinary tract infections (2.3-2.7%), which are generally manageable 2, 6

Contraindications to Verify

• eGFR <20 mL/min/1.73m² 2, 6
• History of serious hypersensitivity to empagliflozin 2
• Polycystic kidney disease or recent immunosuppressive therapy for kidney disease 2

Critical Clinical Pitfalls to Avoid

1. Do not withhold empagliflozin because the patient lacks diabetes—cardiovascular benefits are independent of glucose-lowering effects and occur equally in non-diabetic patients. 2, 4, 8

2. Do not wait for "optimization" of other medications—empagliflozin provides additive benefit regardless of background therapy and requires no titration. 3, 6

3. Do not discontinue for mild eGFR decline—a transient drop in eGFR after initiation is expected and provides long-term kidney protection. 2, 6

4. Do not substitute other SGLT2 inhibitors without heart failure trial data—only empagliflozin and dapagliflozin have dedicated outcome trials in heart failure. 3, 6

Comparison with Alternative SGLT2 Inhibitors

Both empagliflozin and dapagliflozin are considered equivalent and interchangeable for heart failure treatment, with the choice guided by formulary availability and cost. 6

• Dapagliflozin reduced worsening heart failure or cardiovascular death by 18% (HR 0.82,95% CI 0.73-0.92) in the DELIVER trial (HFmrEF/HFpEF population). 3, 6
• Empagliflozin reduced the same composite by 21% (HR 0.79,95% CI 0.69-0.90) in EMPEROR-Preserved. 1, 4
• Both carry Class I, Level A recommendations from ACC/AHA/HFSA for heart failure therapy regardless of diabetes status. 6

Mechanism of Benefit Beyond Glucose Control

The cardiovascular benefits of empagliflozin in this non-diabetic patient occur through direct cardiovascular mechanisms:

• Favorable reverse left ventricular remodeling with reduction in LV volumes 5
• Natriuresis and enhanced diuretic efficacy through proximal tubular sodium-glucose reabsorption inhibition 6
• Shift in cardiac metabolism toward more efficient ketone utilization 6
• Reduction in cardiac fibrosis and adverse remodeling 6
• Preservation of kidney function through afferent arteriolar vasoconstriction that prevents glomerular hyperfiltration 6