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.1
|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:||
|Possible Side Effects:||
|Hydralazine & Isosorbide Dinitrate|
|How it is given:||Pill|
|What it is used for:||
|You should not be treated with it if:||
|Possible Side Effects:||
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).1 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.3
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.1
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.1 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.4 These benefits were seen in both women and men, with no significant difference between the sexes.5,6
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.1 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.7 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.1
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.8
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?
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
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:
- 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.
See also: Nitrates for Coronary Artery Disease
- Hunt SA, Abraham WT, Chin MH, et al. 2009 Focused update incorporated into the ACC/AHA 2005 Guidelines for the Diagnosis and Management of Heart Failure in Adults A Report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines Developed in Collaboration With the International Society for Heart and Lung Transplantation. J Am Coll Cardiol. Apr 14 2009;53(15):e1-e90.
- Hale TW. Medications & Mother's Milk. 13 ed. Amarillo, TX: Hale Publishing, L.P.; 2008.
- Elkayam U, Johnson JV, Shotan A, et al. Double-blind, placebo-controlled study to evaluate the effect of organic nitrates in patients with chronic heart failure treated with angiotensin-converting enzyme inhibition. Circulation. May 25 1999;99(20):2652-2657.
- Taylor AL, Ziesche S, Yancy C, et al. Combination of isosorbide dinitrate and hydralazine in blacks with heart failure. N Engl J Med. Nov 11 2004;351(20):2049-2057.
- Taylor AL, Ziesche S, Yancy CW, et al. Early and sustained benefit on event-free survival and heart failure hospitalization from fixed-dose combination of isosorbide dinitrate/hydralazine: consistency across subgroups in the African-American Heart Failure Trial. Circulation. Apr 3 2007;115(13):1747-1753.
- Taylor AL, Lindenfeld J, Ziesche S, et al. Outcomes by gender in the African-American Heart Failure Trial. J Am Coll Cardiol. Dec 5 2006;48(11):2263-2267.
- Mullens W, Abrahams Z, Francis GS, et al. Usefulness of Isosorbide Dinitrate and Hydralazine as add-on therapy in patients discharged for advanced decompensated heart failure. Am J Cardiol. Apr 15 2009;103(8):1113-1119.
- Cohn JN, Johnson G, Ziesche S, et al. A comparison of enalapril with hydralazine-isosorbide dinitrate in the treatment of chronic congestive heart failure. N Engl J Med. Aug 1 1991;325(5):303-310.
- Yancy CW, Ghali JK, Braman VM, et al. Evidence for the continued safety and tolerability of fixed-dose isosorbide dinitrate/hydralazine in patients with chronic heart failure (the extension to African-American Heart Failure Trial). Am J Cardiol. Aug 15 2007;100(4):684-689.