Is hydralazine (direct vasodilator) a suitable option for a patient with Heart Failure with preserved Ejection Fraction (HFpEF)?

Hydralazine in Heart Failure with Preserved Ejection Fraction (HFpEF)

Hydralazine alone is not recommended for patients with Heart Failure with Preserved Ejection Fraction (HFpEF), as there is no evidence supporting its use as monotherapy in this specific condition. 1

Appropriate Use of Hydralazine in Heart Failure

Hydralazine in HFrEF (not HFpEF)

• Hydralazine is only recommended in combination with isosorbide dinitrate, not as monotherapy, and primarily for patients with Heart Failure with Reduced Ejection Fraction (HFrEF), not HFpEF 1
• The combination of hydralazine and isosorbide dinitrate is specifically recommended for:
  • Self-identified African American patients with NYHA class III-IV HFrEF who are already receiving optimal medical therapy with ACEi/ARB, beta-blockers, and MRA 1
  • Patients with HFrEF who cannot tolerate ACEi, ARB, or ARNi due to drug intolerance, hypotension, or renal insufficiency 1

Evidence for HFpEF

• Current guidelines do not recommend hydralazine (alone or in combination) for HFpEF management 1
• Only preclinical research in animal models suggests potential benefits of combination sodium nitrite and hydralazine therapy in HFpEF, but this has not been validated in human clinical trials 2

Management Recommendations for HFpEF

First-line Approaches for HFpEF

• Systolic and diastolic blood pressure control according to published guidelines is the primary approach for preventing morbidity in HFpEF 1
• Diuretics should be used for symptom relief due to volume overload in HFpEF patients 1

Medication Selection for HFpEF

• For blood pressure control in HFpEF, the following medications are preferred:
  • Diuretics (particularly thiazide or thiazide-like) for volume control and blood pressure management 1
  • ACE inhibitors, ARBs, or beta-blockers may be used for blood pressure control 1

Cautions and Contraindications

Drugs to Avoid in Heart Failure

• Certain medications should be avoided in heart failure patients, including:
  • Non-dihydropyridine calcium channel blockers (verapamil, diltiazem) due to negative inotropic effects 1
  • Moxonidine (and potentially other centrally-acting agents like clonidine) 1
  • Alpha-blockers should be used with caution and only if other agents are inadequate 1
  • NSAIDs should be used with caution as they can worsen renal function and cause fluid retention 1

Practical Considerations

• If hydralazine is used (in combination with nitrates for HFrEF), dosing should be carefully titrated as the beneficial effects seen in clinical trials were at higher doses than typically used in practice 1
• Adherence can be challenging due to the complexity of the regimen and potential adverse effects 1

Emerging Research

• Animal studies suggest that combination therapy with sodium nitrite and hydralazine may have potential benefits in HFpEF by restoring NO bioavailability and reducing oxidative stress, but this requires further clinical validation 2
• The combination of hydralazine and nitrates has arterial and venous vasodilating properties that can decrease preload and afterload, but these benefits have only been established in HFrEF, not HFpEF 3, 4