What is the 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 an SGLT2 inhibitor (dapagliflozin 10 mg or empagliflozin 10 mg once daily) immediately as first-line disease-modifying therapy, combined with loop diuretics titrated to relieve congestion, while aggressively managing hypertension, diabetes, and obesity. 1, 2, 3

First-Line Disease-Modifying Pharmacotherapy

SGLT2 inhibitors are the cornerstone of HFpEF treatment and should be initiated in all patients regardless of diabetes status. 4, 1, 2

• Dapagliflozin 10 mg daily reduced the composite endpoint of worsening heart failure and cardiovascular death by 18% (HR 0.82,95% CI 0.73-0.92) and heart failure hospitalizations by 23% (HR 0.77,95% CI 0.67-0.89) in the DELIVER trial 1, 2, 3
• Empagliflozin 10 mg daily reduced heart failure hospitalization or cardiovascular death by 21% (HR 0.79,95% CI 0.69-0.90) in EMPEROR-PRESERVED 4, 1, 2, 3
• These benefits occur independent of glucose-lowering effects and represent a Class 2a recommendation from the 2022 ACC/AHA/HFSA guidelines 4, 1
• Ensure eGFR >30 mL/min/1.73m² for dapagliflozin and >60 mL/min/1.73m² for empagliflozin before initiation 1

Immediate Symptom Management with Diuretics

Loop diuretics must be started immediately to relieve congestion but should be titrated to the lowest effective dose to maintain euvolemia. 1, 2, 3

• Start furosemide 20-40 mg daily (or bumetanide 0.5-1.0 mg, or torsemide 5-10 mg) based on congestion severity 1, 2, 3
• Train patients to self-adjust diuretic doses based on daily weight monitoring—increases of 2-3 pounds over 2-3 days warrant dose escalation 3
• Avoid excessive diuresis, which leads to hypotension, renal dysfunction, and reduced cardiac output—particularly problematic in HFpEF where cardiac output is already compromised 1, 3
• If inadequate response despite dose increases, consider switching to a different loop diuretic or adding a thiazide for sequential nephron blockade 1

Blood Pressure Management

Target blood pressure <130/80 mmHg using medications already prescribed for heart failure, with RAAS antagonists as first-line agents for additional control. 4, 1, 2, 3

• The SGLT2 inhibitor and loop diuretic will contribute to blood pressure control 3
• ACE inhibitors or ARBs are reasonable for additional blood pressure control if needed, given their experience in HFpEF trials, though they have not shown mortality benefit 4, 3
• Beta-blockers may be used for blood pressure control and are particularly reasonable if atrial fibrillation is present for rate control 4, 3

Additional Pharmacological Options for Selected Patients

Consider adding spironolactone 12.5-25 mg daily (titrating to 50 mg) particularly if LVEF is in the lower preserved range (40-50%). 4, 1, 2, 3

• Spironolactone has a Class 2b recommendation based on the TOPCAT trial showing reduction in heart failure hospitalizations (HR 0.83,95% CI 0.69-0.99) but no significant mortality benefit 4, 1, 3
• Monitor potassium and renal function closely—check within 1 week of initiation and after dose changes, as hyperkalemia is a significant risk 3

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. 4, 1, 2

• The overall PARAGON-HF trial did not achieve a significant reduction in the primary composite endpoint (rate ratio 0.87; 95% CI 0.75-1.01; p=0.06) 1
• Prespecified subgroup analyses showed potential benefit in patients with LVEF below the median (45%-57%) (rate ratio 0.78; 95% CI 0.64-0.95) and in women (rate ratio 0.73; 95% CI 0.59-0.90) 1

Diabetes Management in HFpEF Patients

For patients with diabetes, the SGLT2 inhibitor provides dual benefits for both conditions and should be the first-line agent regardless of glycemic control needs. 3

• If additional glucose lowering is needed after starting an SGLT2 inhibitor, prioritize GLP-1 receptor agonists (such as semaglutide, dulaglutide, or liraglutide) which provide additional cardiovascular protection 3
• Metformin can be continued or added for glycemic control but does not provide specific heart failure benefits 3
• Avoid thiazolidinediones (pioglitazone, rosiglitazone) entirely, as they cause fluid retention and worsen heart failure 2, 3

Obesity Management

For obese patients with HFpEF, diet-induced weight loss produces clinically meaningful increases in functional capacity and quality of life. 5

• GLP-1 receptor agonists can be particularly beneficial in this population, providing both weight loss and cardiovascular protection 3

Non-Pharmacological Interventions

Prescribe supervised exercise training programs (Class 1 recommendation) as they improve aerobic exercise capacity by 12-14% and quality of life with clinically meaningful benefits. 1, 2, 5

• 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 1
• Recommend dietary sodium restriction to <2-3 g/day to help control volume status and reduce congestion 2, 3
• Education in HF self-care (adherence to medications and dietary restrictions, monitoring of symptoms and vital signs) can help avoid HF decompensation 5

Critical Medications to Avoid

Never use nondihydropyridine calcium channel blockers (diltiazem, verapamil), as they have negative inotropic effects and increase the risk of heart failure worsening and hospitalization. 2

• Avoid nitrates, as they are associated with a signal of harm in HFpEF and routine use is ineffective for increasing activity or quality of life 4, 2
• Use NSAIDs with extreme caution due to effects on blood pressure, volume status, and renal function 2
• Avoid centrally acting agents like moxonidine, which was associated with increased mortality in heart failure 2
• Use alpha-blockers (doxazosin) with caution or avoid, as the ALLHAT trial showed a 2-fold increase in risk of developing heart failure 2

Monitoring and Follow-Up

Assess volume status, renal function, electrolytes, and symptoms at each visit, adjusting diuretic doses based on congestion status. 1, 3

• Regular monitoring is particularly important when using MRAs due to hyperkalemia risk 1, 3
• Monitor functional capacity to guide treatment adjustments 1
• Consider wireless, implantable pulmonary artery monitors in selected patients for optimizing volume status 1

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. 1, 6

• Medications that are highly effective in HFrEF (such as beta-blockers, ACE inhibitors, ARBs) have not shown mortality benefit in HFpEF, though they may reduce hospitalizations 6
• The burden of non-cardiac comorbidities increases as LVEF increases, requiring comprehensive comorbidity management 6
• Do not overlook the importance of managing comorbidities such as hypertension, diabetes, obesity, and atrial fibrillation, which significantly impact outcomes in HFpEF 1, 2

Advanced Treatment Options

For patients with advanced HFpEF refractory to standard therapies, consider referral to an advanced heart failure specialist team. 1

• Cardiac transplantation can be considered in eligible patients with advanced HFpEF 1

Current Evidence on Mortality Reduction

No pharmacological agent has definitively shown isolated mortality reduction in HFpEF; SGLT2 inhibitors reduce composite cardiovascular outcomes driven primarily by reductions in heart failure hospitalizations rather than mortality alone. 1, 6

• Multiple other agents, including perindopril, irbesartan, beta-blockers, digoxin, ivabradine, sildenafil, and serelaxin, have failed to show any mortality benefit in HFpEF 1
• The goal of therapy in HFpEF is to alleviate symptoms, improve quality of life, and reduce hospitalizations 1, 5