Vasodilators (afterload and preload reduction).

• Hydralazine mainly causes arteriolar vasodilation.
• Nitrates mainly cause venous dilation.

Therefore, it is important to combine nitrates + hydralazine to obtain both arteriolar and venous vasodilation

• Decrease in afterload and preload, resulting in a decrease in intracardiac filling pressures.
• Decrease in symptoms of exertional dyspnoea.
• Decrease in the tendency to dampness and water retention.

Trial: V-HeFT I trial (1986) and A-HeFT trial (Taylor et al. NEJM 2004)

• Decrease in mortality
• Improvement of LVEF
• Improved exercise capacity

Today there are only limited indications:           

• These medications or the combination of both is primarily an alternative to ACE inhibitors, ARB or ARNI when they must be stopped or can only be prescribed in low doses in progressive severe renal insufficiency (GFR < 15-20 ml/min, for dialysis) and /or hyperkalemia.
• These medications or their combination can possibly be added to standard therapy with neurohormonal blockers as additional afterload reduction in persistent symptomatic heart failure if there is no hypotension after reaching the optimal dose of ACE inhibitor/ARB and beta blocker.
• In African Americans, the addition of high-dose hydralazine 37.5 mg and isosorbide dinitrate 20 mg 3 times/day on top of standard heart failure therapy demonstrated a positive effect on mortality in the A-HeFT study. Note that the standard of care heart failure therapy at that time consisted only of ACE inhibitors/ARB, spironolactone, beta blocker and digoxin.

• Isosorbide dinitrate (Cedocard): start with 20 mg 0.5 tablet 3 x / day, to increase good tolerance to 3 x 20 mg to 3 x 40 mg per day.
  DO NOT use the 5 mg sublingual melting tablets for this indication. These are fast-acting and short-acting. Too high a dose increases the risk of symptomatic hypotension.

• Hydralazine (can be prescribed magisterially): start with 6.25 or 12.5 mg 3 to 4 times a day, to increase good tolerance to 25 to 50 mg 3 to 4 times a day.

• Often used in patients who are admitted and treated with intravenous Nitroprusside to gradually switch from intravenous medication to this peroral treatment after stabilization.
• Data from the V-HeFT trial are from 1986. The background therapy for congestive HF then consisted only of diuretics and digoxin. This therapy was therefore never tested in combination with the current standard of care treatment.

• Hypersensitivity to hydralazine or nitrates

• Hypotension
• Headache (with nitrates)
• Hydralazine is sometimes associated with drug induced lupus. Incidence: 10-15%. Symptoms: serositis, arthralgias, myalgias and fever.