What treatment adjustment is recommended for a 62-year-old female with hypothyroidism, hypertension, and heart failure with improved ejection fraction, currently experiencing New York Heart Association (NYHA) Class II symptoms, and taking sacubitril/valsartan (valsartan and sacubitril) 49 mg/51 mg orally twice daily, carvedilol 25 mg orally twice daily, and furosemide (frusemide) 40 mg orally daily, to reduce her risk of heart failure rehospitalization and cardiovascular death?

Recommended Treatment Change

Start empagliflozin 10 mg orally daily to reduce this patient's risk of heart failure rehospitalization and cardiovascular death. 1

Rationale for SGLT2 Inhibitor Addition

This patient with HFrEF (LVEF 45%) and NYHA Class II symptoms is already on three foundational therapies (sacubitril/valsartan, carvedilol, and furosemide) but is missing the fourth pillar of guideline-directed medical therapy (GDMT): an SGLT2 inhibitor. 1

The American College of Cardiology/American Heart Association/Heart Failure Society of America recommends initiating four foundational medication classes as soon as possible after diagnosis, including:

• Renin-angiotensin system inhibitors (already on sacubitril/valsartan)
• Beta-blockers (already on carvedilol)
• Mineralocorticoid receptor antagonists (MRA) - notably absent
• Sodium-glucose cotransporter 2 inhibitors (SGLT2i) - notably absent 1

SGLT2 inhibitors reduce cardiovascular death and heart failure hospitalization regardless of diabetes status, making them essential for all HFrEF patients. 1 They have minimal blood pressure effects (only -1.50 mmHg in patients with baseline SBP 95-110 mmHg), making them ideal for early initiation even in patients with borderline blood pressure like this one (110/75 mmHg). 1

Why Not the Other Options?

Increasing Carvedilol Dose

The patient is already on carvedilol 25 mg twice daily, which is the target maintenance dose for beta-blocker therapy in HFrEF. 1 Further dose escalation is not indicated and would not provide additional mortality benefit. The evidence-based beta-blockers (carvedilol, metoprolol succinate, bisoprolol) should be titrated to maximally tolerated doses proven in clinical trials, and this patient has already achieved that target. 2, 1

Increasing Furosemide Dose

The patient has no edema or rales on auscultation, indicating she is euvolemic. 1 Loop diuretics are essential for congestion control but do not reduce mortality—they are purely symptomatic therapy. 1 Increasing furosemide in a euvolemic patient would risk dehydration, electrolyte abnormalities, and renal dysfunction without improving cardiovascular outcomes. 2 The guideline principle is to titrate diuretic dose to achieve euvolemia, then use the lowest dose that maintains this state. 1

Starting Ivabradine

Ivabradine is only indicated for patients who:

1. Remain symptomatic despite optimal therapy
2. Are in sinus rhythm
3. Have heart rate ≥70 bpm
4. Are on maximally tolerated beta-blocker doses 1

This patient has a heart rate of 69 bpm, which is below the threshold for ivabradine consideration. 1 Additionally, the European Journal of Heart Failure indicates that ivabradine's survival benefit is modest or negligible in the broad HFrEF population, making it a less compelling choice than SGLT2 inhibitors. 1

Critical Missing Therapy: Mineralocorticoid Receptor Antagonist

Beyond the SGLT2 inhibitor, this patient is also missing an MRA (spironolactone or eplerenone), which is another foundational therapy. The ACC/AHA guidelines recommend aldosterone receptor antagonists for patients with NYHA class II through IV heart failure who have an ejection fraction of 35% or less. 2

While this patient's LVEF is 45% (heart failure with improved ejection fraction), the European Society of Cardiology recommends MRAs for all symptomatic patients with LVEF ≤35% to reduce mortality and hospitalization, providing at least 20% mortality reduction. 1 Given her LVEF of 45%, she may not meet strict criteria for MRA initiation, but this should be reconsidered if her LVEF decreases or symptoms worsen.

Implementation Strategy

Start empagliflozin 10 mg orally daily immediately. 1 SGLT2 inhibitors can be initiated without complex titration protocols and have minimal blood pressure effects, making them safe to start alongside her current regimen. 1 The patient's blood pressure of 110/75 mmHg is adequate for SGLT2 inhibitor initiation, as GDMT medications have proven efficacy and safety across all baseline systolic blood pressure levels, with benefits maintained even in patients with SBP <110 mmHg. 1

Common Pitfalls to Avoid

• Do not delay SGLT2 inhibitor initiation waiting to optimize other therapies—all four foundational classes should be started as soon as possible after diagnosis. 1
• Do not withhold therapy for asymptomatic low blood pressure with adequate perfusion. 1
• Do not increase diuretics in euvolemic patients—this risks adverse effects without mortality benefit. 2, 1
• Do not accept suboptimal doses of foundational therapies, but recognize when target doses have been achieved (as with this patient's carvedilol). 1

Monitoring After SGLT2 Inhibitor Initiation

Monitor for:

• Volume depletion (though rare with SGLT2 inhibitors)
• Genital mycotic infections (more common in women)
• Euglycemic diabetic ketoacidosis (if diabetic)
• Renal function and electrolytes at 1-2 weeks, then at 3 months, then every 6 months 3