Heart Failure with Reduced Ejection Fraction Management

Guideline-Directed Medical Therapy (GDMT) for HFrEF

The American College of Cardiology recommends initiating all four medication classes (ACEi/ARB/ARNi, beta-blockers, MRAs, and SGLT2i) simultaneously at low doses as soon as HFrEF is diagnosed, regardless of symptom severity, with sequential uptitration to target doses as tolerated 1, 2
The American College of Cardiology suggests that all four medication classes should be started early in the disease course for patients with HFrEF (LVEF ≤40%) 1, 2
The American Heart Association recommends that medications may be initiated simultaneously at low doses or sequentially, without waiting to achieve target doses before starting the next medication 3
The American College of Cardiology recommends starting with low doses as recommended in guidelines (e.g., bisoprolol, spironolactone) and uptitrating doses at 2-week intervals if the preceding dose was well tolerated 2
The American College of Cardiology suggests continuing uptitration even if symptoms improve at lower doses, as clinical trials demonstrated benefits at target doses 4, 2

The American College of Cardiology recommends that ARNi (sacubitril/valsartan) is preferred over ACEi/ARB in NYHA class II-III patients to further reduce morbidity and mortality 3
The American Heart Association suggests that one of three evidence-based beta-blockers (bisoprolol, carvedilol, metoprolol succinate) should be used 3
The American College of Cardiology recommends that beta-blockers reduce mortality by 34% (the highest relative risk reduction among the four classes) 4, 2
The American College of Cardiology suggests that MRAs provide substantial mortality benefit with NNT of 6 over 36 months 4

The American College of Cardiology recommends that SGLT2i have a Class 2a recommendation for Heart Failure with Mildly Reduced Ejection Fraction (HFmrEF, LVEF 41-49%) 1
The European Society of Cardiology suggests that treatment of hypertension is a Class 1 recommendation for Heart Failure with Preserved Ejection Fraction (HFpEF, LVEF ≥50%) 1, 5

The American College of Cardiology recommends assessing renal function and electrolytes before initiation and periodically thereafter 2
The American Heart Association suggests evaluating for clinical improvement in symptoms, exercise tolerance, and quality of life 6

The American College of Cardiology recommends avoiding delaying initiation of all four medication classes due to concerns about polypharmacy 1, 2
The American College of Cardiology suggests avoiding failing to uptitrate to target doses used in clinical trials 4, 2
The American Heart Association recommends avoiding discontinuing medications when LVEF improves 1

The American College of Cardiology recommends choosing one beta-blocker to continue, either bisoprolol or metoprolol succinate, as both are guideline-recommended, but never both simultaneously 7, 8
The current bisoprolol dose is only 25% of target, while metoprolol succinate dose is not specified but target is 200 mg daily, and one beta-blocker should be discontinued immediately and the remaining one uptitrated toward target dose before adding empagliflozin 7, 8

The American College of Cardiology recommends SGLT2 inhibitors, such as empagliflozin or dapagliflozin, as Class 1A recommendations for all patients with HFrEF to reduce cardiovascular mortality and heart failure hospitalizations 7
The 2022 ACC/AHA/HFSA guidelines recommend initiating all four medication classes, including SGLT2i, simultaneously at low doses as soon as HFrEF is diagnosed 7

Empagliflozin is fully compatible with the patient's current regimen, including sacubitril/valsartan, spironolactone, and beta-blockers, once beta-blocker duplication is corrected 7, 8

The American College of Cardiology recommends starting empagliflozin 10 mg once daily in the morning, with no titration required, as 10 mg daily is the evidence-based dose from clinical trials 7, 8
Before initiating empagliflozin, verify eGFR >20 mL/min/1.73m², adequate volume status, and no active diabetic ketoacidosis 7

The American College of Cardiology recommends uptitrating sacubitril/valsartan every 2-4 weeks to target dose, and continuing spironolactone 25 mg daily with potassium monitoring 7, 8

Empagliflozin actually has mild potassium-lowering effects, which may partially offset the hyperkalemia risk from ARNi + MRA 7
The American College of Cardiology recommends monitoring potassium at baseline, 1 week, 4 weeks, then monthly for 3 months, then every 6 months, and adjusting spironolactone dose accordingly 7