Current Guideline Medications for Diastolic Heart Failure (HFpEF)
SGLT2 inhibitors (empagliflozin or dapagliflozin) are the first-line disease-modifying therapy for HFpEF, with the strongest evidence for reducing heart failure hospitalizations and cardiovascular mortality. 1
First-Line Pharmacotherapy
SGLT2 Inhibitors (Class 2a Recommendation)
- Empagliflozin or dapagliflozin should be initiated in all patients with HFpEF (LVEF ≥50%) regardless of diabetes status. 1, 2
- These agents reduce the composite endpoint of heart failure hospitalization and cardiovascular death by approximately 20% (HR 0.79-0.82). 2, 3
- Empagliflozin requires eGFR >60 mL/min/1.73m², while dapagliflozin requires eGFR >30 mL/min/1.73m². 2
Diuretics for Symptom Management
- Loop diuretics (furosemide 20-40 mg initially, bumetanide 0.5-1.0 mg, or torasemide 5-10 mg) should be used at the lowest effective dose to achieve euvolemia. 1, 2
- Titrate based on daily weights and symptoms to avoid excessive diuresis, which can cause hypotension and renal dysfunction. 1, 2
- If inadequate response occurs, increase the loop diuretic dose before adding a thiazide (avoid thiazides if eGFR <30 mL/min). 1, 2
Second-Line Pharmacotherapy (Class 2b Recommendations)
Mineralocorticoid Receptor Antagonists (MRAs)
- Spironolactone 12.5-25 mg daily may be considered, particularly in patients with LVEF in the lower preserved range (40-50%). 1, 2
- This reduces heart failure hospitalizations (HR 0.83) but did not show mortality benefit in TOPCAT. 2, 3
- Monitor potassium and renal function closely to prevent hyperkalemia. 2, 3
Angiotensin Receptor-Neprilysin Inhibitors (ARNi)
- Sacubitril/valsartan may be considered for selected patients, especially women and those with LVEF 45-57%. 1
- The PARAGON-HF trial showed a trend toward benefit (rate ratio 0.87, p=0.06) that was significant in subgroups with lower LVEF and women. 1, 2
Angiotensin Receptor Blockers (ARBs)
- ARBs (candesartan, valsartan) may be considered to decrease hospitalizations, particularly in patients with LVEF closer to 50%. 1, 3
- The CHARM-Preserved trial showed no reduction in the primary endpoint, but there was a trend toward reduced hospitalizations. 1
Essential Comorbidity Management (Class 1 Recommendation)
Blood Pressure Control
- Hypertension must be aggressively treated to target <130/80 mmHg using guideline-directed antihypertensive medications. 1, 2, 3
Atrial Fibrillation Management (Class 2a Recommendation)
- Rate control of atrial fibrillation is useful to improve symptoms. 1
- Beta-blockers or rate-limiting calcium channel blockers (verapamil, diltiazem) can be used for rate control in HFpEF, unlike in HFrEF. 1
Medications to Avoid (Class 3: No Benefit)
- Nitrates and phosphodiesterase-5 inhibitors (sildenafil) should not be routinely used, as they do not improve activity or quality of life. 1
- Thiazolidinediones and saxagliptin should be avoided due to increased heart failure risk. 3
Treatment Algorithm
- Start with SGLT2 inhibitor (empagliflozin or dapagliflozin) as foundational therapy 1, 2
- Add loop diuretic at lowest effective dose for congestion management 1, 2
- Optimize blood pressure to target <130/80 mmHg 1, 2
- Consider adding MRA if LVEF is 40-50% and patient tolerates monitoring 1, 2
- Consider ARNi for women or those with LVEF 45-57% 1
- Manage atrial fibrillation with rate control if present 1
Critical Pitfalls to Avoid
- Do not treat HFpEF patients identically to HFrEF patients—ACE inhibitors, ARBs, and beta-blockers lack mortality benefit in HFpEF unless indicated for other conditions (hypertension, coronary disease, atrial fibrillation). 4, 5
- Avoid excessive diuresis, which reduces cardiac output in HFpEF and causes hypotension and renal dysfunction. 1, 2
- Do not use diltiazem or verapamil with beta-blockers in atrial fibrillation patients. 3
- Monitor potassium and renal function closely when using MRAs to prevent life-threatening hyperkalemia. 2, 3