What is the optimal medication regimen for a patient with hypertensive heart disease and heart failure with preserved ejection fraction (left‑ventricular ejection fraction 60‑65%, grade I diastolic dysfunction), currently taking nifedipine extended‑release 90 mg daily, carvedilol 25 mg twice daily, isosorbide mononitrate extended‑release 30 mg daily, and hydrochlorothiazide 100 mg three times daily, with a history of hypertensive urgency?

Optimal Medication Regimen for HFpEF with Hypertensive Heart Disease

Critical Medication Changes Required

Your current regimen needs significant modification: discontinue isosorbide mononitrate immediately, add an SGLT2 inhibitor as first-line disease-modifying therapy, and reconsider the appropriateness of nifedipine and hydralazine in favor of evidence-based HFpEF therapies.

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Immediate Actions: Discontinue Ineffective/Harmful Medications

Stop Isosorbide Mononitrate

• Nitrates are ineffective and potentially harmful in HFpEF 1
• The NEAT-HFpEF trial randomized 110 patients with EF ≥50% to isosorbide mononitrate vs. placebo and found no beneficial effects on activity levels, quality of life, exercise tolerance, or NT-proBNP levels 1
• Routine use of nitrates in HFpEF carries a Class III: No Benefit recommendation from the 2022 ACC/AHA/HFSA guidelines 1
• The only exception is if the patient has symptomatic coronary artery disease requiring nitrates for angina relief 1

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Add First-Line Disease-Modifying Therapy

Initiate SGLT2 Inhibitor (Class 2a Recommendation)

Start either dapagliflozin 10 mg daily OR empagliflozin 10 mg daily immediately 1, 2

• This is the cornerstone of HFpEF treatment with the strongest evidence for reducing heart failure hospitalizations and cardiovascular outcomes 2, 3
• EMPEROR-Preserved showed empagliflozin reduced HF hospitalization or cardiovascular death by 21% (HR 0.79,95% CI 0.69-0.90), driven by a 29% reduction in HF hospitalizations 1, 2
• DELIVER trial showed dapagliflozin reduced worsening HF and cardiovascular death by 18% (HR 0.82,95% CI 0.73-0.92) and HF hospitalizations by 23% (HR 0.77,95% CI 0.67-0.89) 2, 3
• Benefits occur independent of diabetes status and represent a class effect for cardiovascular protection 2, 3
• Ensure eGFR >30 mL/min/1.73m² before initiation 3

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Optimize Current Medications

Carvedilol 25 mg Twice Daily - CONTINUE

• Beta-blockers are reasonable in HFpEF, particularly for blood pressure control and rate control if atrial fibrillation develops 1, 3
• The J-DHF study showed that standard doses of carvedilol (>7.5 mg/day) significantly reduced cardiovascular death and hospitalization (HR 0.539,95% CI 0.303-0.959) in HFpEF patients 4
• Your current dose of 25 mg twice daily (50 mg/day total) is appropriate and should be continued 4
• Monitor for chronotropic incompetence, as this can contribute to exercise intolerance in some HFpEF patients 1

Nifedipine ER 90 mg Daily - REASSESS

• Dihydropyridine calcium channel blockers like nifedipine are not specifically recommended for HFpEF in current guidelines 1
• However, nifedipine can be used for blood pressure control in hypertensive heart disease 5
• Given your history of hypertensive urgency, nifedipine may be appropriate for blood pressure management, but RAAS antagonists (ACE inhibitors, ARBs, or ARNi) should be considered as first-line agents for additional blood pressure control given their experience in HFpEF trials 1, 2
• Target blood pressure <130/80 mmHg 1, 2, 3

Hydralazine 100 mg Three Times Daily - RECONSIDER

• Hydralazine is not evidence-based therapy for HFpEF and does not appear in any guideline recommendations for this condition 1
• This medication is primarily used in HFrEF (reduced ejection fraction) as part of the hydralazine-isosorbide dinitrate combination, particularly in African American patients 1
• Consider discontinuing or replacing with evidence-based HFpEF therapy such as an ACE inhibitor, ARB, or mineralocorticoid receptor antagonist 1, 2

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Consider Adding Additional Evidence-Based Therapies

Mineralocorticoid Receptor Antagonist (Class 2b Recommendation)

Consider adding spironolactone 12.5-25 mg daily, particularly since your LVEF of 60-65% is in the preserved range 1, 2

• The TOPCAT trial showed spironolactone reduced HF hospitalizations (HR 0.83,95% CI 0.69-0.99) in HFpEF patients 1, 2, 3
• Greater benefit is seen in patients with LVEF on the lower end of the preserved spectrum (closer to 45-50%) 1, 2
• Critical monitoring required: Check potassium and renal function within 1 week of initiation and after dose changes 1, 3
• Creatinine should be <2.5 mg/dL in men or <2.0 mg/dL in women (or eGFR >30 mL/min) and potassium should be <5.0 mEq/L before initiation 1

Angiotensin Receptor-Neprilysin Inhibitor (Class 2b Recommendation)

Sacubitril/valsartan may be considered as an alternative to ACE inhibitor/ARB, particularly if you are female or have LVEF 45-57% 1, 2

• The PARAGON-HF trial showed 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, 2
• However, the primary endpoint was not met in the overall population 1
• This is a Class 2b recommendation (may be considered) 1

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Diuretic Management for Congestion

Loop Diuretic - ADD IF NEEDED

• Loop diuretics should be used at the lowest effective dose to manage congestion and relieve symptoms 1, 2, 3
• Start furosemide 20-40 mg daily (or bumetanide 0.5-1.0 mg, or torsemide 5-10 mg) and titrate based on symptoms, weight, and volume status 3
• Avoid excessive diuresis, which can lead to hypotension, renal dysfunction, and reduced cardiac output—particularly problematic in HFpEF 3, 6
• Train yourself to self-adjust diuretic doses based on daily weight monitoring and symptoms of congestion 3

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Blood Pressure Management Strategy

Target Blood Pressure <130/80 mmHg

• Strict blood pressure control is essential given your history of hypertensive urgency and hypertensive heart disease 1, 2, 3
• The SPRINT trial established that intensive blood pressure control in patients with high cardiovascular risk significantly reduces HF and other cardiovascular outcomes 1
• RAAS antagonists (ACE inhibitors, ARBs, or ARNi) should be first-line agents for additional blood pressure control given their experience in HFpEF trials 1, 2
• The SGLT2 inhibitor, beta-blocker (carvedilol), and potentially MRA will contribute to blood pressure control 3

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Recommended Medication Regimen

Continue:

1. Carvedilol 25 mg twice daily 4

Add:

1. Dapagliflozin 10 mg daily OR empagliflozin 10 mg daily (first-line disease-modifying therapy) 1, 2, 3
2. Spironolactone 12.5-25 mg daily (monitor potassium and renal function closely) 1, 2, 3
3. Loop diuretic (furosemide 20-40 mg daily) if congestion present 3

Discontinue:

1. Isosorbide mononitrate 30 mg daily (ineffective in HFpEF) 1

Reassess/Replace:

1. Nifedipine ER 90 mg daily - Consider replacing with ACE inhibitor or ARB for blood pressure control 1, 2
2. Hydralazine 100 mg three times daily - Consider discontinuing as it lacks evidence in HFpEF 1

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Critical Monitoring Parameters

• Potassium and renal function: Check within 1 week of starting spironolactone and after dose changes 1, 3
• Blood pressure: Monitor closely given history of hypertensive urgency, target <130/80 mmHg 1, 2, 3
• Volume status: Assess at each visit and adjust diuretic doses based on congestion 3
• Symptoms and functional capacity: Monitor to guide treatment adjustments 2
• Daily weight monitoring: Train patient to self-adjust diuretics based on weight changes 3

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Common Pitfalls to Avoid

• Do not continue nitrates in HFpEF unless symptomatic coronary artery disease is present 1
• Avoid nondihydropyridine calcium channel blockers (diltiazem, verapamil) as they have negative inotropic effects and increase risk of HF worsening 2
• Do not delay initiation of SGLT2 inhibitors, which have the strongest evidence for reducing HF hospitalizations 2, 3, 6
• Avoid excessive diuresis leading to hypotension and renal dysfunction 3, 6
• Do not treat HFpEF patients the same as HFrEF patients, as response to therapies differs 2