Vasodilators & Nitrates in Heart Failure

What are vasodilators and nitrates?

Vasodilators are a class of medications that cause blood vessels to widen (dilate). Nitrates are the most common type of vasodilator medication. They are sometimes given to women with heart failure to relieve symptoms that persist after treatment with the standard medications.

Nitrates are also combined with the high blood pressure drug hydralazine in a single pill to treat heart failure in African-Americans who are already receiving a beta-blocker and either an ACE inhibitor or ARB. African Americans may not respond as well as whites to ACE inhibitors, the first-choice blood pressure drugs for heart failure, which is why additional medication may be needed in these patients. This combination of nitrates and hydralazine may also be used in other patients who have symptoms despite standard treatment.

Hydralazine is used together with nitrates because nitrates widen the veins and hydralazine widens the arteries, making the combination more effective than either drug alone. Hydralazine may also have other effects that prevent the progression of heart failure.

In women with coronary artery disease, nitrates are used to prevent and relieve chest pain (angina).

Nitrates
Generic: Nitroglycerin, Isosorbide mononitrate, Isosorbide dinitrate
Brands: Nitro-Dur, Nitrostat, Nitrolingual , Imdur, Monoket, Dilatrate, Isordil, Sorbitrate
How it is given: Pill or tablet, skin patch, spray, injection (in the hospital)
What it is used for:
  • Prevention of chest pain (angina) due to coronary artery disease
  • Acute relief of an attack of angina due to coronary artery disease
  • Treating heart failure symptoms that have not responded to other treatments
Possible Side Effects: Headache, rapid pulse, flushing, sweating, dizziness, lightheadedness, nausea, vomiting
Pregnancy/Nursing: The safety of nitrates during pregnancy and nursing is not known. If breastfeeding is desired, do so with caution at higher doses and with prolonged exposure. Observe the infant for signs that they are not receiving enough oxygen (shortness of breath, skin turning blue).

 

Hydralazine & Isosorbide Dinitrate
Brands: BiDil
How it is given: Pill
What it is used for:
  • To treat heart failure in African-Americans or patients who cannot take ACE inhibitors or ARBs
  • Added to standard treatment in women who still have symptomsPrevention of chest pain (angina) due to coronary artery disease
You should not be treated with it if:
  • You have not tried taking ACE inhibitors or ARBs
  • You should be monitored carefully if you have coronary artery disease or have suffered a heart attack
Possible Side Effects: Headache, dizziness, loss of appetite, nausea, vomiting, diarrhea, pounding/ fast heartbeat
Pregnancy/Nursing: The safety of this medication during pregnancy is unknown, so it should be used with caution; it is not known if either drug is transferred to breast milk and should be used only if the potential benefits outweigh the risks.

Who should receive nitrates and hydralazine to treat heart failure?

Nitrate pills are often given to women who continue to suffer from shortness of breath and other heart failure symptoms after treatment with standard medications (an ACE inhibitor or ARB, a beta-blocker, and a diuretic). Nitrates can relieve symptoms, improve your ability to exercise, and improve the heart’s pumping ability, but there is no evidence they lower your chances of dying.

A combination of hydralazine and a nitrate should be given to African Americans who still have moderate to severe heart failure symptoms after standard treatment.

A combination of hydralazine and a nitrate may also be considered for women who cannot take ACE inhibitors or ARBs because of the side effects, or because they have kidney problems.

What are the benefits of hydralazine and a nitrate?

African Americans benefit from adding a combination pill of hydralazine and a nitrate to standard heart failure treatment. In a trial of 1050 African American patients with moderate to severe heart failure symptoms (40% were women), adding the combo pill decreased the chances of dying by 43%, reduced hospitalizations for heart failure by a third, and improved quality of life. These benefits were seen in both women and men, with no significant difference between the sexes.

Patients with advanced systolic heart failure who continue to have symptoms may benefit from adding hydralazine and a nitrate to their standard treatment regimen, even if they are not African American. In one study of 239 patients (20% were women), this add-on therapy lowered the chances of dying or being hospitalized for heart failure by almost 30% for patients overall. This study was too small to determine if women and men benefited equally.

There have been no trials of add-on therapy with hydralazine and nitrates in patients who cannot take an ACE inhibitor or ARB because of side effects or other reasons (such as kidney problems). Still, treatment guidelines state it is reasonable to used this drug combination in these patients because there are few other options.

Who should not receive nitrates or hydralazine?

Hydralazine and a nitrate should not be used to treat women with heart failure who have never tried taking an ACE inhibitor, and should not be substituted for an ACE inhibitor in women who are not having problems tolerating the drug. This is because ACE inhibitors alone are better than hydralazine and a nitrate alone at improving survival.

Because hydralazine can speed up the heart rate, sometimes not enough blood is supplied to the heart muscle to keep up with this faster rate, causing chest pain. This is especially common in women who already have damage to the arteries that supply blood to the heart, so hydralazine should be used carefully in women who have had a heart attack or who have coronary artery disease.

What side effects should I watch for?

Nitrates

The most common side effects of nitrates are a throbbing headache (in about 50% of people), warmness and flushing of the skin, and dizziness or lightheadedness. These side effects are not serious and usually become less severe with continued use of the medication. If the headache persists, your doctor may try to eliminate this side effect by lowering your dose.

Other possible non-serious side effects include a fast pulse, restlessness, and nausea or vomiting. Rarely, more serious side effects can occur when taking nitrates. Let your doctor know as soon as possible if you have any of these symptoms:

  • blurred vision
  • dry mouth
  • severe or prolonged headache
  • skin rash
  • blue-colored lips, fingernails, or palms
  • extreme dizziness or fainting
  • shortness of breath
  • weak and fast heartbeat
  • fever
  • convulsions

Combination Therapy with Hydralazine and a Nitrate

The most common side effects of combination therapy are headache (34% of patients) and dizziness (16%) of patients.9 These side effects are equally common in women and men.5 As many as 1 in 5 patients may need to stop taking the medication because of side effects. You may also experience loss of appetite, nausea, vomiting, and a pounding or racing heartbeat as your body adjusts to the medication, but these will usually go away over time. If any of these effects persist or worsen, tell your doctor or pharmacist.

Very serious side effects of these drugs are rare, but you should seek immediate medical attention if you experience:

  • rash
  • itching or swelling (especially of the face, tongue, or throat)
  • severe dizziness
  • trouble breathing
  • swollen glands
  • bloody or pink urine
  • signs of infection such as fever, chills, persistent sore throat
  • easy bruising or bleeding

Hydralazine can interact with some other medications, so talk to your doctor if you are taking an MAO inhibitor, a class of drugs used to treat depression. If you are taking other blood pressure lowering drugs you are at risk for developing dangerously low blood pressure (hypotension), so talk to you doctor about what to watch for and what you can do to make sure your blood pressure stays in a safe range.

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