Therapy for Chronic Heart Failure: A Two-pronged Approach

Dr.Wong is a pharmacy practice resident at Hackensack University Medical Center, Hackensack, NJ. Dr. Pham is an assistant professor of pharmacy practice at Western University of Health Sciences, College of Pharmacy, Pomona, Calif.

Chronic heart failure (CHF) is a condition that results from any structural or functional cardiac disorder that impairs the ability of the heart to fill with or pump a sufficient amount of blood through the body. The disease affects nearly 5 million Americans, and the number of heart failure- related deaths has risen rapidly, despite advances in treatment.¹ The incidence of CHF approaches 10 per 1000 after the age of 65.¹

In the United States, 2 major guidelines are used in the diagnosis and management of patients with CHF. The American College of Cardiology and the American Heart Association collaborated with the American College of Chest Physicians and the International Society for Heart and Lung Transplantation to release a guideline in 2005.¹ In 2006, the Heart Failure Society of America (HFSA) produced a similar guideline.² For the sake of brevity, this article reviews both guidelines and summarizes the recommendations.

Diagnosis

CHF is classified into 4 stages based on the degree of functional limitation on the New York Heart Association (NYHA) classification scale.¹ The most common symptom that results from left ventricular failure is dyspnea, or a sense of breathlessness. Dyspnea is caused by decreased lung compliance that results from pulmonary edema and congestion.³ It is most commonly noticeable during periods of physical activity.³ Exertional dyspnea is the number one reason for patients with CHF to seek medical attention. 3 Other symptoms include fluid retention, abnormal heart sounds or electrocardiogram, or evidence of cardiac enlargement or dysfunction. A complete history and physical examination are the first steps in evaluating CHF.

The single most effective diagnostic test is a comprehensive 2-dimensional echocardiogram combined with Doppler flow studies to determine myocardium abnormalities. This information produces an objective numerical estimate of the ejection fraction and will assist in the diagnosis of the patient.

Natriuretic peptides, such as brain natriuretic peptide (BNP), are synthesized by and released from the heart. Elevated plasma BNP levels have been associated with a reduction in left ventricular ejection fraction (LVEF).

Pharmacologic Therapy

Pharmacologic therapy consists of 2 major components in chronic heart failure patients: (1) therapy that improves patient mortality (ie, angiotensin-converting enzyme inhibitors [ACEIs], β-blockers, aldosterone antagonists, angiotensin receptor blockers [ARBs], and oral nitrate/hydralazine combination), and (2) therapy that provides symptomatic relief (ie, diuretics, digoxin).

Understanding therapy that is used to maintain or improve patient outcome revolves around the pathophysiology of heart failure and the renin-angiotensinaldosterone system (RAAS). ACEIs inhibit the conversion of angiotensin I to angiotensin II. Angiotensin II is a by-product of the RAAS, which is responsible for arteriole vasoconstriction, sodium absorption in the kidneys, and aldosterone production.⁴ In accordance with the HFSA 2006 guideline, an ACEI may be used in symptomatic and asymptomatic patients with LVEF ≤40%.² In order for mortality benefit to be seen, ACEIs are always titrated to a target dose.

Although ACEIs have been shown to have beneficial effects in other disease states such as diabetes mellitus and chronic kidney disease, their use may be limited in patients who are intolerant of the adverse event of chronic cough. Hence, an alternative that has been set forth are ARBs. ARBs block the angiotensin II receptor. With similar indications as those used for ACEIs, ARBs may also be considered in patients who have exhibited angioedema while taking an ACEI.² Management of heart failure with the coadministration of an ACEI and an ARB is not recommended, however, in patients with left ventricular dysfunction or a recent acute myocardial infarction.²

Aldosterone is a contributory neurohormone in heart failure leading to unfavorable renal and cardiovascular effects (ie, sodium/water retention, myocardial ischemia, arrhythmia, heart failure). In the Randomized Aldactone Evaluation Study, aldosterone antagonists were found to play a significant role in the management of heart failure and improving patient mortality.^2,4 Spironolactone (Aldactone) should be used in addition to standard therapy such as ACEIs and diuretics.² Special precaution should be taken in the use of aldosterone antagonists in hyperkalemic or renally compromised patients as determined by potassium and creatinine levels, respectively.^2,4

According to the HFSA, β-blockers are recommended in addition to ACEIs in asymptomatic patients with LVEF ≤40%.² Particular β-blockers that have been advocated to have beneficial effects include metoprolol succinate (Toprol XL), carvedilol (Coreg), and bisoprolol (Zebeta).² β-blockers should be initiated at low doses and titrated slowly based on patient tolerance.^2,5 It is important to recognize that β-blockers should not be initiated in symptomatic or acute decompensated heart failure.²

An oral nitrate/vasodilator combination of isosorbide dinitrate/hydralazine (BiDil) offers beneficial effects in conjunction with standard therapy in black patients. Supportive evidence of this recommendation comes from the African-American Heart Failure Trial.⁶

Diuretics are used to provide symptomatic relief in cases of fluid overload due to sodium and water retention. Loop diuretics such as furosemide (Lasix) and bumetanide (Bumex) are preferred over thiazide and potassiumsparing diuretics.² Patients should be monitored for electrolyte abnormalities in addition to clinical response. Additionally, digoxin may be used in symptomatic heart failure with LVEF ≤40% while receiving conventional therapy of β-blockers and ACEIs.²

Nonpharmacologic Therapy

Management of CHF can be optimized with appropriate lifestyle modifications. The HFSA recommends dietary sodium restriction to 2 g to 3 g per day.² Even with lack of supportive evidence to demonstrate improved clinical outcome, dietary sodium restriction would promote hemodynamic stability in heart failure patients. In cases of severe hyponatremia, fluid restriction may be necessary and should not exceed 2 L per day.² Patients are advised to limit alcohol consumption to ≤2 and 1 drink(s) in men and women, respectively.² Patients should be assessed and counseled on smoking cessation. Without appropriate action, the vasoconstrictive properties of nicotine may worsen the clinical status of a patient.² The HFSA also recommends pneumococcal and annual influenza vaccines in patients with heart failure.² Moreover, adherence to treatment plans and appropriate patient education are vital components of the successful management of heart failure patients.

Conclusion

CHF is a chronic debilitating disease that may result in significant morbidity and mortality if untreated. There are 2 major guidelines used by many clinicians, and both are similar in nature as to which medications should be used and how to use them. The diagnosis of CHF uses a functional limitation classification based on the NYHA scale. Pharmacologic therapy is separated into medications that decrease mortality and medications that lower morbidity. As pharmacists, we must emphasize the importance of adherence to medications used in CHF, especially those that have proven mortality benefit. Pharmacists should be familiar with providing key counseling points for all agents used in CHF. For example, some agents, such as β-blockers, require slow titration to minimize adverse effects. This information should be provided with discharge counseling or medication pick-up at the pharmacy.

Case Scenarios

• A patient returns to the clinic for a routine checkup without complaints. Since her last visit to your clinic, she has suffered a myocardial infarction 4 months ago and has an ejection fraction of 35%. Her current medications include enalapril 7.5 mg po bid, furosemide 20 mg po qd, aspirin 325 mg po qd, glyburide 5 mg po qd, and simvastatin 20 mg po every evening. Her vital signs are heart rate 58 bpm and blood pressure 120/80 mm Hg. Her lungs are clear, and laboratory tests are within normal limits.Which of the following is the best management of this patient's drug regimen? Continue therapy Stop aspirin and start warfarin to an international normalized ratio of 2 to 3; increase furosemide to 40 mg po qd Start carvedilol 25 mg po bid and begin digoxin because both agents reduce mortality in chronic heart failure Increase enalapril to 10 mg po bid

• AV is a 60-year-old woman with systolic dysfunction. Her medications at home include enalapril 5 mg po bid, furosemide 40 mg qd, digoxin 0.125 mg qd, and aspirin. Her vitals signs are blood pressure 118/80 and heart rate 78 bpm. Her laboratory tests reveal sodium 143, potassium5.9, chloride 110, bicarbonate 20, blood urea nitrogen 22, creatinine 1.5, and calculated creatinine clearance of 45 mL/minute. She is asymptomatic. Immediate electrocardiogram reveals no new changes. The only change in her laboratory tests during the past 6 months is an increase in her serum potassium.Which of the following agents reduces mortality in congestive heart failure? Digoxin Enalapril Furosemide Aspirin

Answers

• d. Increase enalapril to 10 mg po bid
• b. Enalapril

Click to Read Answers for Case Scenarios: Congestive Heart Failure

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References

• Hunt SA, Abraham WT, Chin MH, et al. ACC/AHA 2005 Guideline update for the diagnosis and management of chronic heart failure in the adult: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Writing Committee to update the 2001 Guidelines for the Evaluation and Management of Heart Failure): developed in collaboration with the American College of Chest Physicians and the International Society for Heart and Lung Transplantation: endorsed by the Heart Rhythm Society. Circulation. 2005;112:e154-e235.
• dams KF, Lindenfeld J, Arnold JMO, et al. HFSA 2006 comprehensive heart failure practice guideline. J Card Fail. 2006;12:e1-e122.
• Burns DK, Kumar V. The heart. In: Kumar V, Cotran RS, Robbins SL, eds. Robbins Basic Pathology. Philadelphia: Saunders. 2003;361-396.
• Odedra K, Ferro A. Neurohormones and heart failure: the importance of aldosterone. Int J Clin Pract. 2006;60:835-846.
• Fowler MB, Lottes SR, Nelson JJ, et al. Beta-blocker dosing in community-based treatment of heart failure. Am Heart J. 2007;153:1029-1036.
• Temple R, Stockbridge NL. BiDil for heart failure in black patients: The US Food and Drug Administrative perspective. Ann Intern Med. 2007;146:57-62.