From the Guidelines
The combination of hydralazine and nitrates provides benefit in heart failure beyond just the African-American population, though the evidence is strongest in Black patients. This combination is recommended for patients with heart failure with reduced ejection fraction (HFrEF) who remain symptomatic despite standard therapy with ACE inhibitors/ARBs, beta-blockers, and mineralocorticoid receptor antagonists, or for those who cannot tolerate these medications due to side effects like hypotension or renal dysfunction, as stated in the 2022 AHA/ACC/HFSA guideline 1. The typical dosing regimen is hydralazine 25-75 mg three times daily and isosorbide dinitrate 20-40 mg three times daily, titrated as tolerated.
Key Points
- The benefit of hydralazine and nitrates in non-African American populations is less clear, but earlier trials like V-HeFT I and II showed benefit in broader populations before racial differences were specifically analyzed 1.
- The mechanism involves complementary vasodilation effects - hydralazine primarily affects arterial vessels while nitrates predominantly dilate venous vessels, reducing both afterload and preload.
- Monitoring for side effects including headache, dizziness, and lupus-like syndrome is important when initiating this therapy.
- Referral to a HF specialist can provide guidance for further management because the use of hydralazine and isosorbide dinitrate in patients who cannot receive first-line agents is uncertain, as noted in the 2022 guideline 1.
Considerations
- The 2013 ACCF/AHA guideline recommends the combination of hydralazine and isosorbide dinitrate for African Americans with HFrEF who remain symptomatic despite concomitant use of ACE inhibitors, beta blockers, and aldosterone antagonists 1.
- The benefit in both trials was seen only at doses achieved in those trials that are higher than doses typically used in clinical practice and with short-acting nitrate therapy, as mentioned in the 2022 guideline 1.
- Uptake of this regimen has been modest as a result of the complexity of the medical regimen and the array of drug-related adverse effects.
From the Research
CHF Benefit for Hydralazine and Nitrates
- The combination of hydralazine and nitrates has been shown to have a beneficial effect on heart failure with reduced ejection fraction (HFrEF) in certain populations 2, 3, 4.
- However, the evidence suggests that this benefit is mainly seen in African American patients 4, 5.
- In the African American Heart Failure Trial (A-HeFT), the combination of hydralazine and nitrates reduced mortality by 43% compared to placebo in African American patients with HFrEF 2.
- A systematic review of randomized trials found that the combination of hydralazine and nitrates reduced all-cause mortality and cardiovascular mortality in patients with CHF, but this benefit was not seen when compared to angiotensin-converting enzyme inhibitors (ACEIs) 6.
- There is limited evidence to support the use of hydralazine or nitrates alone in the treatment of CHF, and they may be inferior to ACEIs 6.
- The use of hydralazine and nitrates in non-African American populations is not well established, and more research is needed to determine their effectiveness in these groups 2, 3, 5.