What is the role of hydralazine in myocardial infarction (MI)?

Role of Hydralazine in Myocardial Infarction (MI)

Hydralazine is not recommended as monotherapy in myocardial infarction due to potential risks of provoking myocardial ischemia, but may be used in combination with isosorbide dinitrate in specific patient populations with heart failure following MI, particularly in African American patients or those intolerant to ACE inhibitors. 1

Mechanism and Risks in MI

• Hydralazine is an arterial vasodilator with relatively little effect on venous tone and cardiac filling pressures 1
• It can provoke myocardial ischemic events in patients with coronary artery disease due to:
  • Reflex tachycardia which increases myocardial oxygen demand 2
  • Preservation of elevated left ventricular preload (unlike nitrates which reduce preload) 3
  • "Hyperdynamic" circulation that may accentuate specific cardiovascular inadequacies 2
• Case reports document myocardial infarction following hydralazine overdose 4
• In a study of 52 patients with heart failure due to coronary artery disease, 23% experienced ischemic events with hydralazine administration, including 4 myocardial infarctions 3

Appropriate Use in Post-MI Heart Failure

• Hydralazine is primarily used in combination with isosorbide dinitrate rather than as monotherapy in heart failure following MI 1
• The combination provides complementary effects:
  • Hydralazine: arterial vasodilation
  • Isosorbide dinitrate: venous vasodilation 1
• This combination has shown mortality benefit in specific populations:
  • African American patients with NYHA class III-IV heart failure (Class I recommendation) 1
  • Patients who cannot tolerate ACE inhibitors (Class IIa recommendation) 1

Clinical Trial Evidence

• Large-scale trials showed the hydralazine-isosorbide dinitrate combination reduced mortality (but not hospitalizations) in heart failure patients treated with digoxin and diuretics 1
• However, ACE inhibitors produced more favorable effects on survival compared to the hydralazine-isosorbide dinitrate combination 1
• A confirmatory trial specifically in African American patients showed significant benefit when adding hydralazine-isosorbide dinitrate to standard therapy with ACE inhibitors and/or beta blockers 1

Practical Considerations

• Hydralazine should not be used as first-line therapy for heart failure post-MI when patients can tolerate ACE inhibitors 1
• Common side effects include:
  • Headache and gastrointestinal complaints 1
  • Hypotension 2
  • Tachycardia 2, 5
• Compliance challenges exist due to:
  • Multiple daily doses required
  • High incidence of adverse reactions 1
• Dosing may be complicated by acetylator status, with wide dosage ranges reported (150-3000 mg/24h) 6

Monitoring and Precautions

• ECG monitoring is advisable when initiating therapy due to potential for ischemic changes 2, 3
• Blood pressure monitoring is essential as hydralazine can cause significant hypotension 2
• Long-term monitoring should include:
  • Complete blood counts
  • Antinuclear antibody titer determinations to detect drug-induced lupus syndrome 2
• Use with caution in patients with:
  • Suspected coronary artery disease
  • Cerebrovascular disease
  • Advanced renal damage 2

Alternative Approaches in Acute MI with Left Ventricular Failure

• In acute heart failure following MI, other agents may be preferable:
  • Venodilators like isosorbide dinitrate showed greater reduction in LV filling pressure with less tachycardia compared to hydralazine 5
  • Diuretics (furosemide) also demonstrated favorable hemodynamic effects 5