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Drug Treatments for Chronic Heart Failure

Worst Pills, Best Pills Newsletter article January, 2016

Chronic heart failure affects approximately 5 million Americans.[1] In 2013, the American College of Cardiology (ACC) and the American Heart Association (AHA) released guidelines on evaluating and treating heart failure,[2] the first major update of their recommendations on heart failure since 2009.[3]

About heart failure

Heart failure occurs when the heart is no longer able to receive blood from or pump blood to the rest of the body at normal levels. The most common causes of...

Chronic heart failure affects approximately 5 million Americans.[1] In 2013, the American College of Cardiology (ACC) and the American Heart Association (AHA) released guidelines on evaluating and treating heart failure,[2] the first major update of their recommendations on heart failure since 2009.[3]

About heart failure

Heart failure occurs when the heart is no longer able to receive blood from or pump blood to the rest of the body at normal levels. The most common causes of heart failure are high blood pressure, coronary heart disease and diabetes,[4] all of which can damage the heart’s muscles over time, especially if not treated properly.

The severity of heart failure is determined by the heart’s pumping effectiveness and by the level of activity limitation that causes symptoms.[5] Common symptoms include swelling, often in the legs; shortness of breath; and nighttime cough — symptoms that are often accompanied by excess fluid in the body. While some patients experience few or no symptoms, even with normal activity levels, the most severely ill have trouble breathing with any level of physical activity or even at rest. Heart failure often is fatal, with half of all patients dying within five years of their diagnosis.[6]

Guideline recommendations

The goals of heart failure treatment are to improve daily symptoms and quality of life; to reduce the frequency of sudden worsening of symptoms, including episodes requiring hospitalization; and to enable patients to live longer. The ACC and AHA tailored their 2013 treatment recommendations based on two main factors: the heart’s pumping effectiveness[7] and the presence of heart failure symptoms.[8]

The guidelines’ treatment recommendations were focused mainly on patients whose hearts fail to pump blood normally, a condition called systolic heart failure. The guidelines recommend that all of these patients receive treatment with an angiotensin-converting enzyme (ACE) inhibitor and a beta blocker, regardless of whether they have symptoms. The exception to this general guideline is when patients cannot take ACE inhibitors or beta blockers because of unacceptable side effects or safety concerns.

For certain patients whose hearts are pumping normally, the guidelines recommend only that drugs known as angiotensin II receptor blockers (ARBs) be considered to decrease hospitalizations for heart failure.

For patients with weakly pumping hearts who also develop symptoms, the guidelines recommend a few additional medications. Digoxin (LANOXIN), a heart rhythm medication that also may improve heart muscle orgfunction, is recommended to reduce heart failure hospitalizations and death risk,[9] while diuretics can reduce swelling that can result from too much fluid in the body.[10] Medications known as aldosterone receptor antagonists (see table, below) are recommended for patients who have been hospitalized for cardiovascular disease in the past or have signs of too much fluid in their bodies, unless they have certain conditions, such as kidney disease or high potassium blood levels.[11]

A combination of hydralazine and isosorbide dinitrate (BIDIL) was shown to reduce the risk of death only in African-American patients[12],[13] and is therefore recommended for African-Americans for whom mild physical activity produces heart failure symptoms.[14] (Since BIDIL may not be readily available, doctors may instead prescribe separately the generic forms of hydralazine and isosorbide dinitrate at doses similar to those found in BIDIL.)[15]

Our take

We largely agree with the guideline recommendations, with a few exceptions. For heart failure patients with weakly pumping hearts, ACE inhibitors,[16] beta blockers,[17] diuretics,[18] aldosterone antagonists[19],[20] and digoxin[21] all have been shown to reduce the risk of death or hospitalization and therefore should be considered. African-American patients with weakly pumping hearts and symptoms during mild physical activity also should be on hydralazine-isosorbide dinitrate.

By contrast, a 2011 review of studies showed that no drug, including ARBs, seems effective in reducing the risk of death or total hospitalizations (for either heart failure or other conditions) in symptomatic patients whose hearts are pumping at normal levels (a condition known as diastolic heart failure).[22],[23] So we disagree with the guidelines’ recommendation to consider ARBs in such patients.[24]

We also do not think that ARBs are a reasonable alternative to ACE inhibitors, unless ACE inhibitors are ineffective or have side effects, such as cough, that cannot be tolerated. The evidence for the benefits of ARBs in heart failure is not as clear as that for ACE inhibitors.[25]

And patients should never take both ACE inhibitors and ARBs, as this combination has no added benefit over one of these drugs alone, while increasing the risk of kidney failure, low blood pressure and dangerously high blood potassium levels.[26]

See the table below for a list of the oral medications approved by the Food and Drug Administration for the treatment of heart failure. While effective in patients with weakly pumping hearts, they come with serious risks. All can cause low blood pressure at excessive doses. ACE inhibitors, ARBs and aldosterone receptor antagonists also can lead to kidney failure and high blood potassium levels.[27] Diuretics may cause kidney failure, dehydration and dangerous electrolyte abnormalities.[28] Digoxin can lead to fatal heart rhythm disorders at high doses or upon interaction with multiple other drugs,[29] and blood levels of the drug therefore must be carefully monitored on an ongoing basis.

Oral Medications
Approved for Heart Failure*

ACE inhibitors
captopril (generic only)**
enalapril (EPANED, VASOTEC)**
fosinopril (generic only)**
lisinopril (PRINIVIL, ZESTRIL)**
quinapril (ACCUPRIL)
ramipril (ALTACE)***
trandolapril (MAVIK)***
ARBs
candesartan (ATACAND)**
valsartan (DIOVAN)**
Beta blockers
carvedilol (COREG, COREG CR)
metoprolol (TOPROL XL)
Diuretics
bumetanide (generic only)**
chlorothiazide (DIURIL)
chlorthalidone (generic only)
ethacrynic acid (EDECRIN)
furosemide (LASIX)**
hydrochlorothiazide (generic only)
hydroflumethiazide (SALURON)
methyclothiazide (generic only)
metolazone (ZAROXOLYN)
torsemide (DEMADEX)
Aldosterone antagonists
eplerenone (INSPRA)***
spironolactone (ALDACTONE)**
Other
digoxin (LANOXIN)
hydralazine-isosorbide dinitrate (BIDIL)**
*Besides BIDIL, we did not include any combination medicines in this table.
**Classified as a Limited Use medicine on Worstpills.org. However, for heart failure, see this article for our advice as to which medicines to use.
***Approved only for heart failure that occurs following a heart attack.

What You Can Do

If you are diagnosed with heart failure, the appropriate treatment depends on both the severity of your symptoms and the results of tests to measure whether your heart is pumping normally. If these tests are normal, your treatment should be aimed at relieving any symptoms you experience, such as swelling or shortness of breath, for which a diuretic may help. Hydrochlorothiazide should be the first diuretic tried for mild cases of swelling, with furosemide (LASIX) the main option for more severe cases.

If the tests show, however, that your heart is pumping weakly, you should be on beta blockers and ACE inhibitors (or ARBs if you cannot take or tolerate ACE inhibitors), even if you do not have symptoms, as these are lifesaving therapies. If you also start to experience symptoms, then a diuretic, an aldosterone antagonist, digoxin and, if you are African American, hydralazine-isosorbide dinitrate should be added to your regimen.

Other, nondrug treatments, such as a defibrillator or a device to improve your heart rhythm,[30] may be necessary depending on the severity of your heart failure. If you are symptomatic, you should limit the amount of sodium in your diet[31] to prevent fluid from building up and causing symptoms.

It is very important to adequately treat certain diseases — such as high blood pressure, coronary heart disease, kidney disease or diabetes — that could affect the course of heart failure in the long term.

Always discuss the risks of potential treatments with your doctor.

References

[1] Centers for Disease Control and Prevention. Heart Failure Fact Sheet. http://www.cdc.gov/dhdsp/data_statistics/fact_sheets/fs_heart_failure.htm. Accessed October 19, 2015.

[2] Yancy CW, Jessup M, Bozkurt B, et al. 2013 ACCF/AHA guideline for the management of heart failure: A report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. Circulation. 2013;128:e240-e327.

[3] American Heart Association. ACC/AHA Joint Guidelines: By topic and year. http://my.americanheart.org/professional/StatementsGuidelines/ByTopic/TopicsA-C/ACCAHA-Joint-Guidelines_UCM_321694_Article.jsp#.ViVZLX6rSUk. Accessed October 19, 2015.

[4] National Heart, Lung, and Blood Institute. What causes heart failure? http://www.nhlbi.nih.gov/health/health-topics/topics/hf/causes. Accessed October 19, 2015.

[5] 2013 ACC/AHA Guidelines, at e248.

[6] Centers for Disease Control and Prevention. Heart Failure Fact Sheet. http://www.cdc.gov/dhdsp/data_statistics/fact_sheets/fs_heart_failure.htm. Accessed October 19, 2015.

[7] 2013 ACC/AHA Guidelines, at e261, e274.

[8] 2013 ACC/AHA Guidelines, at e248, e260. .

[9] 2013 ACC/AHA Guidelines, at e271.

[10] 2013 ACC/AHA Guidelines, at e265.

[11] 2013 ACC/AHA Guidelines, at e269.

[12] Carson P, Ziesche S, Johnson G, Cohn JN. Racial differences in response to therapy for heart failure: Analysis of the vasodilator-heart failure trials. Vasodilator-Heart Failure Trial Study Group. J Card Fail. 1999;5(3):178-87.

[13] Taylor AL, Ziesche S, Yancy C, et al. Combination of isosorbide dinitrate and hydralazine in blacks with heart failure. N Engl J Med. 2004;351(20):2049-57.

[14] 2013 ACC/AHA Guidelines, at e270.

[15] 2013 ACC/AHA Guidelines, at e280-283.

[16] Garg R, Yusuf S. Overview of randomized trials of angiotensin-converting enzyme inhibitors on mortality and morbidity in patients with heart failure. JAMA. 1995;273(18):1450-6.

[17] McAlister FA, Wiebe N, Ezekowitz JA, et al. Meta-analysis: Beta-blocker dose, heart rate reduction, and death in patients with heart failure. Ann Intern Med. 2009;150(11):784-94.

[18] Faris RF, Flather M, Purcell H, et al. Diuretics for heart failure. Cochrane Database Syst Rev. 2012;2:CD003838.

[19] Zannad F, McMurray JJ, Krum H, et al. Eplerenone in patients with systolic heart failure and mild symptoms. N Engl J Med. 2011;364(1):11-21.

[20] Pitt B, Zannad F, Remme WJ, et al. The effect of spironolactone on morbidity and mortality in patients with severe heart failure. N Engl J Med. 1999;341(10):709-17.

[21] Hood WB Jr, Dans AL, Guyatt GH, Jaeschke R, McMurray JJ. Digitalis for treatment of heart failure in patients in sinus rhythm. Cochrane Database Syst Rev. 2014;4:CD002901.

[22] Oghlakian GO, Sipahi I, Fang JC. Treatment of heart failure with preserved ejection fraction: have we been pursuing the wrong paradigm? Mayo Clin Proc. 2011;86(6):531-9.

[23] Heran BS, Musini VM, Bassett K, Taylor RS, Wright JM. Angiotensin receptor blockers for heart failure. Cochrane Database Syst Rev. 2012;4:CD003040.

[24] 2013 ACC/AHA Guidelines, at e274.

[25] Heran BS, Musini VM, Bassett K, Taylor RS, Wright JM. Angiotensin receptor blockers for heart failure. Cochrane Database Syst Rev. 2012;4:CD003040.

[26] Public Citizen. Petition to the FDA for Black Box Warnings on ACE Inhibitors, ARBs, and Aliskiren. October 4, 2012. http://www.citizen.org/documents/20751.pdf. Accessed October 20, 2015. Also see: 2013 ACC/AHA Guidelines, at e267.

[27] 2013 ACC/AHA Guidelines, at e267, e269.

[28] 2013 ACC/AHA Guidelines, at e265.

[29] 2013 ACC/AHA Guidelines, at e271.

[30] 2013 ACC/AHA Guidelines, at e274.

[31] 2013 ACC/AHA Guidelines, at e263.

Clarification:  The table in this article did not include a complete list of drugs currently approved for treating heart failure by the Food and Drug Administration. Among the drugs omitted from the table was ivabradine (CORLANOR), approved for heart failure in April 2015. At this time, we have designated this drug as Do Not Use for Seven Years. And as noted in the footnote to the table, with the exception of hydralazine-isosorbide dinitrate (BIDIL), combination medicines also were excluded.