How should I manage a patient with heart failure caused by long‑standing hypertension, including optimal blood‑pressure control and guideline‑directed therapy for reduced ejection fraction?

Management of Hypertensive Heart Failure

Immediately initiate all four foundational guideline-directed medical therapy (GDMT) classes simultaneously—SGLT2 inhibitor, mineralocorticoid receptor antagonist (MRA), beta-blocker, and ARNI (or ACE inhibitor if ARNI not tolerated)—along with loop diuretics for volume control, targeting a blood pressure of <130/80 mmHg while aggressively uptitrating to target doses regardless of blood pressure readings above 100 mmHg systolic. 1, 2

Blood Pressure Targets in Hypertensive Heart Failure

Target systolic/diastolic blood pressure of <130/80 mmHg with a lower safety threshold of >120/70 mmHg for patients with heart failure and reduced ejection fraction (HFrEF). 2 This target is extrapolated from hypertension guidelines and applies to most patients with hypertensive heart failure. 1

• For elderly patients (generally >65-70 years), a slightly less aggressive target of <140/80 mmHg may be acceptable, though <130/80 mmHg remains preferred when tolerated. 2
• Systolic and diastolic blood pressure should be controlled in accordance with published clinical practice guidelines to prevent morbidity in patients with heart failure and preserved ejection fraction (HFpEF). 1
• The optimal blood pressure goal and antihypertensive regimens are not definitively established for patients with HFpEF, but treatment should follow similar strategies to HFrEF. 1

Foundational Quadruple GDMT for HFrEF

Start all four medication classes simultaneously as soon as possible after diagnosis, beginning with SGLT2 inhibitor and MRA first since they have minimal blood pressure effects. 1, 2, 3

1. SGLT2 Inhibitors (First Priority)

• Dapagliflozin 10 mg once daily (if eGFR ≥20 mL/min/1.73 m²) or empagliflozin 10 mg once daily (if eGFR ≥30 mL/min/1.73 m²). 2, 3
• Produces minimal SBP reduction (average -1.5 mmHg, falling to <1 mmHg after 4 months), making it ideal for patients with borderline blood pressure. 2
• Reduces cardiovascular death and heart failure hospitalization regardless of diabetes status, with benefits occurring within weeks of initiation. 1, 3
• No dose titration required—maximal benefit achieved at starting dose. 3

2. Mineralocorticoid Receptor Antagonists (First Priority)

• Spironolactone 12.5-25 mg daily or eplerenone 25 mg daily for patients with NYHA class II-IV symptoms and LVEF ≤35%. 1, 2, 4
• Provides at least 20% mortality reduction and reduces sudden cardiac death with negligible blood pressure impact. 2, 3
• Can be used if eGFR >30 mL/min/1.73 m² and potassium <5.0 mEq/L. 1, 3
• Uptitrate to spironolactone 25-50 mg daily or eplerenone 50 mg daily as tolerated. 2

3. Beta-Blockers (Second Priority)

• Use only evidence-based beta-blockers: carvedilol, metoprolol succinate, or bisoprolol. 1, 3
• Provide the largest relative mortality reduction (≈34%) among GDMT classes and should not be withheld for SBP 100-130 mmHg. 2, 3
• Start at low doses and uptitrate every 1-2 weeks to target doses:
  • Carvedilol: 3.125 mg twice daily → 25 mg twice daily (50 mg twice daily if >85 kg)
  • Metoprolol succinate: 12.5-25 mg daily → 200 mg daily
  • Bisoprolol: 1.25 mg daily → 10 mg daily 2, 3

4. ARNI (Angiotensin Receptor-Neprilysin Inhibitor) or ACE Inhibitor/ARB

• Sacubitril/valsartan (ARNI) is preferred over ACE inhibitors for symptomatic patients (NYHA class II-IV), providing superior mortality reduction of at least 20%. 1, 3
• Start sacubitril/valsartan 24/26 mg or 49/51 mg twice daily, uptitrating to target dose of 97/103 mg twice daily over 3-6 weeks. 1, 3
• Should be titrated to target dose even when SBP is 100-130 mmHg. 2
• Wait 36 hours after stopping ACE inhibitor before starting ARNI to avoid angioedema risk. 1, 3
• If ARNI not tolerated, use ACE inhibitor (enalapril, lisinopril, ramipril) or ARB (losartan, valsartan, candesartan). 1

5. Loop Diuretics for Volume Management

• Essential for congestion control but do not reduce mortality. 3
• Starting doses: furosemide 20-40 mg once or twice daily, torsemide 10-20 mg once daily, or bumetanide 0.5-1.0 mg once or twice daily. 3
• Titrate to achieve euvolemia (no edema, no orthopnea, no jugular venous distension), then use lowest dose that maintains this state. 3

Blood Pressure-Guided GDMT Initiation Strategy

SBP Range	Recommended Strategy	Rationale
130-160 mmHg	Initiate all four GDMT classes simultaneously	Higher baseline BP allows full-spectrum initiation [2]
110-129 mmHg	Start SGLT2i and MRA first, then add beta-blocker and ARNI	Prioritize medications with minimal BP effect [2]
90-109 mmHg	Begin SGLT2i and MRA; add low-dose beta-blocker or ARNI cautiously	BP-neutral profile of SGLT2i and MRA [2]
<90 mmHg or symptomatic hypotension	Address reversible causes first (stop alpha-blockers, adjust diuretics); start SGLT2i once stable	Eliminate non-HF medications interfering with GDMT [2]

Managing Low Blood Pressure During GDMT Optimization

Never discontinue or down-titrate GDMT for asymptomatic hypotension with adequate perfusion—GDMT medications maintain efficacy and safety even in patients with baseline SBP <110 mmHg. 2, 3

Step 1: Address Reversible Non-HF Causes

• Stop alpha-blockers (tamsulosin, doxazosin, terazosin, alfuzosin) as they interfere with GDMT optimization. 2, 3
• Discontinue other non-essential BP-lowering medications. 2
• Evaluate for dehydration, infection, or acute illness. 2, 3

Step 2: Non-Pharmacological Interventions

• Compression leg stockings for orthostatic symptoms. 3
• Exercise and physical training programs. 3
• Adequate salt and fluid intake if not volume overloaded. 3

Step 3: Adjust GDMT Only If Symptoms Persist

• If heart rate >70 bpm: Reduce ACEi/ARB/ARNI dose first. 3
• If heart rate <60 bpm: Reduce beta-blocker dose first. 3
• Always maintain SGLT2 inhibitor and MRA (minimal BP effects). 3

Additional Therapies for Specific Populations

For Self-Identified Black Patients

• Hydralazine/isosorbide dinitrate is indicated for Black patients with NYHA class III-IV symptoms despite optimal GDMT. 1, 3
• Starting dose: hydralazine 25 mg three times daily + isosorbide dinitrate 20 mg three times daily, uptitrating to hydralazine 75 mg three times daily + isosorbide dinitrate 40 mg three times daily. 1, 3
• Insufficient data for concomitant use with ARNI; monitor BP carefully if combining. 1

For Patients with Persistent Tachycardia

• Ivabradine may be considered if heart rate ≥70 bpm in sinus rhythm despite maximally tolerated beta-blocker. 1, 3
• Starting dose: 2.5-5 mg twice daily, uptitrating to 7.5 mg twice daily. 3
• Survival benefit is modest or negligible in the broad HFrEF population. 3

Management of HFpEF with Hypertension

• Use beta-blocking agents, ACE inhibitors, and ARBs to control blood pressure in patients with HFpEF. 1
• Diuretics should be used for relief of symptoms due to volume overload. 1
• In appropriately selected patients with HFpEF (EF ≥45%, elevated BNP levels or HF admission within 1 year, eGFR >30 mL/min, creatinine <2.5 mg/dL, potassium <5.0 mEq/L), aldosterone receptor antagonists might be considered to decrease hospitalizations. 1
• SGLT2 inhibitors (empagliflozin) showed benefit in HFpEF with LVEF >40%, driven by 29% reduction in HF hospitalization. 1

Monitoring Requirements

Check blood pressure, heart rate, renal function, and electrolytes 1-2 weeks after each GDMT dose increment. 2, 3

• Creatinine rise up to 30% above baseline is acceptable and should not trigger drug discontinuation. 2, 3
• Potassium levels require close monitoring with MRAs; consider potassium binders (patiromer) if hyperkalemia develops rather than discontinuing life-saving medications. 3
• Discontinuing RAAS inhibitors after hypotension is linked to 2- to 4-fold higher risk of adverse events compared with continuation. 2, 3

Critical Contraindications and Medications to Avoid

• Avoid diltiazem and verapamil in HFrEF—they increase risk of worsening heart failure and hospitalization. 1, 3
• Do not combine ACE inhibitor with ARNI due to angioedema risk. 1, 3
• Avoid triple combination of ACE inhibitor + ARB + MRA due to hyperkalemia and renal dysfunction risk. 1, 3
• Discontinue alpha-blockers as they impede GDMT optimization. 2, 3
• Do not use non-evidence-based beta-blockers (e.g., atenolol, metoprolol tartrate). 3

Common Pitfalls to Avoid

• Delaying initiation of all four medication classes—simultaneous or rapid sequential initiation is recommended. 1, 3
• Accepting suboptimal doses in the SBP 100-130 mmHg range—clinical trials demonstrate benefit only at target doses. 2, 3
• Stopping medications for asymptomatic hypotension—adverse events occur in 75-85% of HFrEF patients regardless of treatment, with no substantial difference between GDMT and placebo. 3
• Inadequate monitoring of renal function and electrolytes during uptitration. 3
• Withholding beta-blockers for SBP 100-130 mmHg—they provide the greatest mortality reduction and are safe in this range. 2

Expected Mortality Benefit

Optimizing all four foundational GDMT classes yields an ≈73% reduction in 2-year mortality compared to no treatment. 1, 2 Transitioning a 55-year-old patient from traditional dual therapy (ACE inhibitor and beta-blocker) to quadruple medical therapy would extend life expectancy by approximately 6 years. 1