What is the optimal treatment approach for an older adult patient with heart failure with preserved ejection fraction (HFpEF), hypertension, diabetes, and obesity?

Treatment for Heart Failure with Preserved Ejection Fraction (HFpEF)

Start dapagliflozin 10 mg or empagliflozin 10 mg once daily immediately as first-line disease-modifying therapy for all patients with HFpEF, regardless of diabetes status, as this reduces heart failure hospitalizations by 21-23% and the composite of cardiovascular death or worsening heart failure by 18-21%. 1, 2

Disease-Modifying Pharmacotherapy

SGLT2 Inhibitors (First-Line Therapy)

• Initiate either dapagliflozin 10 mg daily or empagliflozin 10 mg daily as the cornerstone of HFpEF treatment (Class 2a recommendation from the American College of Cardiology). 3, 1, 2
• Dapagliflozin reduced worsening heart failure and cardiovascular death by 18% (HR 0.82,95% CI 0.73-0.92) in the DELIVER trial, with a 23% reduction in heart failure hospitalizations specifically (HR 0.77,95% CI 0.67-0.89). 1, 2
• Empagliflozin reduced heart failure hospitalization or cardiovascular death by 21% (HR 0.79,95% CI 0.69-0.90) in EMPEROR-PRESERVED. 1, 2
• Verify eGFR >30 mL/min/1.73m² for dapagliflozin and >60 mL/min/1.73m² for empagliflozin before starting. 2

Mineralocorticoid Receptor Antagonists (Second-Line Consideration)

• Consider adding spironolactone 12.5-25 mg daily (Class 2b recommendation) particularly in patients with LVEF in the lower preserved range (40-50%). 3, 2
• Spironolactone reduced heart failure hospitalizations by 17% (HR 0.83,95% CI 0.69-0.99) in the TOPCAT trial, though it did not reduce the primary composite outcome overall. 2
• Monitor potassium and renal function closely when prescribing spironolactone to minimize hyperkalemia risk. 2

Angiotensin Receptor-Neprilysin Inhibitors (Selective Use)

• Sacubitril/valsartan may be considered (Class 2b recommendation) specifically for women and patients with LVEF 45-57%, as these subgroups showed benefit in PARAGON-HF post-hoc analyses. 3, 2
• The overall PARAGON-HF trial did not achieve statistical significance for the primary endpoint (rate ratio 0.87; 95% CI 0.75-1.01; p=0.06). 2

Symptom Management with Diuretics

Loop Diuretics for Congestion

• Start loop diuretics immediately to relieve congestion: furosemide 20-40 mg daily, bumetanide 0.5-1.0 mg daily, or torsemide 5-10 mg daily. 1, 4, 5
• For acute decompensation with orthopnea or paroxysmal nocturnal dyspnea, use intravenous loop diuretics at a dose greater than or equal to the patient's chronic oral daily dose. 4, 2
• Titrate to the lowest effective dose to maintain euvolemia ("dry weight") based on daily weight monitoring, symptoms, and physical exam findings. 1, 5
• If inadequate response despite dose increases, consider switching to a different loop diuretic or adding a thiazide diuretic for sequential nephron blockade. 2

Management of Comorbidities

Blood Pressure Control

• Target blood pressure <130/80 mmHg using medications already prescribed for heart failure. 1, 2
• Use ACE inhibitors or ARBs as first-line agents for additional blood pressure control if needed beyond SGLT2 inhibitors. 1, 4

Diabetes Management

• Prioritize SGLT2 inhibitors for glycemic control given their dual benefit for both diabetes and heart failure. 4, 2

Obesity Management

• Recommend dietary sodium restriction to <2-3 g/day to help control volume status and reduce congestion. 1
• Diet-induced weight loss produces clinically meaningful increases in functional capacity and quality of life. 5

Non-Pharmacological Interventions

Exercise Training (Class 1 Recommendation)

• Prescribe supervised exercise training programs as this improves aerobic exercise capacity by 12-14% (2.0-2.2 mL/kg/min increase in peak VO2) and quality of life with clinically meaningful benefits. 3, 1, 2
• Exercise training programs typically involve 3 sessions per week for 1-8 months at 40-90% of exercise capacity, using walking, stationary cycling, or high-intensity interval training. 3
• The meta-analysis treatment effect showed a 2.8 mL/kg/min improvement in peak VO2 with exercise training versus control. 3

Heart Failure Self-Care Education

• Educate patients on medication adherence, dietary sodium restriction, daily weight monitoring, and symptom recognition to avoid heart failure decompensation. 5

Critical Medications to Avoid

Absolute Contraindications

• Never use nondihydropyridine calcium channel blockers (diltiazem, verapamil) as they have negative inotropic effects and increase the risk of heart failure worsening and hospitalization. 1, 2
• Avoid thiazolidinediones (pioglitazone, rosiglitazone) entirely as they cause fluid retention and worsen heart failure. 1
• Avoid nitrates as they are associated with a signal of harm in HFpEF. 1

Use with Extreme Caution

• Avoid alpha-blockers (doxazosin) as the ALLHAT trial showed a 2-fold increase in risk of developing heart failure compared with chlorthalidone. 1
• Avoid centrally acting agents like moxonidine, which was associated with increased mortality in heart failure. 1
• Use NSAIDs with extreme caution due to effects on blood pressure, volume status, and renal function. 1

Treatment Algorithm for Older Adults with HFpEF, Hypertension, Diabetes, and Obesity

Step 1: Initiate Disease-Modifying Therapy

• Start SGLT2 inhibitor (dapagliflozin 10 mg or empagliflozin 10 mg daily) immediately. 1, 2

Step 2: Manage Congestion

• If signs of volume overload (orthopnea, edema, elevated JVP), start loop diuretic at appropriate dose. 1, 2
• Titrate diuretic to maintain euvolemia with daily weight monitoring. 1

Step 3: Optimize Blood Pressure

• Target BP <130/80 mmHg using SGLT2 inhibitor effects plus ACE inhibitor or ARB if needed. 1, 2

Step 4: Consider Additional Therapy

• If LVEF is in the lower preserved range (40-50%), add spironolactone 12.5-25 mg daily with close monitoring of potassium and renal function. 3, 2

Step 5: Non-Pharmacological Interventions

• Refer to supervised exercise training program (3 sessions/week). 3, 1
• Recommend sodium restriction <2-3 g/day. 1
• For obesity, recommend diet-induced weight loss. 5

Step 6: Monitoring

• Assess volume status, renal function, and electrolytes regularly, especially with MRA therapy. 2
• Monitor symptoms and functional capacity to guide treatment adjustments. 2

Common Pitfalls to Avoid

• Do not treat HFpEF patients the same as those with reduced ejection fraction, as response to therapies differs significantly between these populations. 2
• Avoid excessive diuresis which may lead to hypotension and worsening renal function. 2
• Do not overlook the importance of managing comorbidities (hypertension, diabetes, obesity, atrial fibrillation), which significantly impact outcomes in HFpEF. 3, 2
• Do not use beta-blockers routinely unless there is a specific indication (prior MI within 3 years, angina, or atrial fibrillation), and monitor for chronotropic incompetence. 3

Important Note on Mortality

No pharmacological agent has been definitively proven to reduce mortality in HFpEF as a standalone outcome. 2 The benefits of SGLT2 inhibitors are driven primarily by reductions in heart failure hospitalizations rather than mortality alone, though they do reduce the composite endpoint of cardiovascular death or worsening heart failure. 2 Therefore, the treatment goal in HFpEF focuses on alleviating symptoms, improving quality of life, and reducing hospitalizations. 2