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APhA Drug Treatment Protocol: Management of Chronic Systolic Heart Failure

[J Am Pharm Assoc 41(5):672-681, 2001. © 2001 American Pharmaceutical Association, Inc.]

Introduction by Daniel H. Albrant
Protocol developed by the Cardiovascular Diseases Protocol Panel


Introduction

As the U.S. population ages, the incidence of heart failure is increasing.

Heart failure affects almost 5 million people in the United States and has 6-year mortality rates approaching 80% in men and 65% in women. Heart failure is the only cardiovascular disease that is increasing in incidence, due in part to the aging of the population. An estimated 400,000 to 700,000 new cases of heart failure are diagnosed in the United States each year. Almost 1 million hospitalizations for treatment of heart failure occur annually at an estimated cost of $8 billion to $15 billion. Ultimately, heart failure causes the deaths of 250,000 people each year.[1]

The heart is said to be failing when it can no longer meet the blood flow requirements of the body. Worsening failure results in an increasing imbalance between blood flow demand and supply, leading to dyspnea on exertion, paroxysmal nocturnal dyspnea, and orthopnea. Heart failure is often secondary to coronary artery disease, hypertension, and/or idiopathic dilated cardiomyopathy.

This drug treatment protocol reviews the management of patients with systolic heart failure, the most common type. The goal of therapy is to prolong the patient's life while providing relief from symptoms and improving quality of life. The first steps in the process are to obtain all pertinent medical and medication histories, and then to evaluate the severity of the illness. Patients with severe symptoms should be referred to the hospital for further management.

Heart failure is classified using the New York Heart Association's functional class rating system. This classification system stratifies the degree of heart failure according to the severity of symptoms and the limitations the condition imposes on the patient's activities, with Class I signifying low severity and no limitations and Class IV signifying extreme severity and limitations.[2] Once the heart failure has been classified, education can begin. Lifestyle modifications and patient education and counseling are key components of any strategy for managing heart failure. Warning signs of worsening heart failure, dietary modifications (e.g., salt restriction), daily weight assessment, and adherence to therapy should all be covered in educational sessions with patients.

The most commonly identified causes of left ventricular (LV) systolic dysfunction in the United States are coronary artery disease, hypertension, and idiopathic dilated cardiomyopathy. The primary goals of therapy are prolongation of the patient's life by slowing, halting, or reversing the LV dysfunction; relief of the patient's heart failure symptoms; and improvement in the patient's quality of life.[3-5] This protocol focuses on the management of systolic dysfunction as the cause of the patient's heart failure.

Up to 30% of patients with a diagnosis of congestive heart failure will have ejection fractions greater than 40% with no valvular disease; thus, they have diastolic dysfunction.[4] In diastolic dysfunction, the ventricle is stiff and/or otherwise noncompliant and, as a result, will not fill completely during diastole. This incomplete filling leads to symptoms of heart failure.

The goal of therapy in patients with diastolic dysfunction is to control symptoms of heart failure by reducing ventricular filling pressure without reducing cardiac output. At present, there are no outcome data to recommend one therapeutic approach over another. If diastolic failure progresses, systolic dysfunction may develop.[2,4]

As detailed in the protocol, all patients with systolic heart failure should be started on an angiotensin-converting enzyme inhibitor (ACEI) unless there is a significant contraindication. In that instance, a combination of isosorbide dinitrate and hydra-lazine should be used. ACEI therapy has been shown to reduce morbidity and mortality, and there is a suggestion that it may slow or prevent disease progression.

The patient should be evaluated for signs of adverse drug effects or fluid overload after 1 to 4 weeks. The latter requires the initiation of a diuretic or thiazide. If volume overload persists despite maximal diuretic therapy, then a trial of a combination of diuretics is warranted.

If heart failure worsens at this point, digoxin should be initiated, probably in combination with a ß-blocker. Increasingly, clinicians are using spironolactone in Class IV heart failure with good results. Patients who have been tried on all of the above therapies are candidates for referral to specialty clinics.

Many employer groups and third party payers are looking for methods to manage chronically ill patients better and at less cost. This drug treatment protocol, when appended to a disease state management initiative, is a tool for achieving these goals. We hope that readers will consider this protocol closely and adapt it to the specific needs of their patients.

References to Introduction

  1. Consensus recommendations for the management of chronic heart failure. On behalf of the Advisory Council to Improve Outcomes Nationwide in Heart Failure. Am J Cardiol. 1999;83(2A):1A-38A.
  2. Agency for Health Care Policy and Research. Heart Failure: Evaluation and Care of Patients with Left-Ventricular Systolic Dysfunction. Rockville, Md: U.S. Department of Health and Human Services; 1994. Clinical Practice Guideline 11. AHCPR publication 94-0612.
  3. Cohn JN. The management of chronic heart failure. N Engl J Med. 1996;335:490-8.
  4. Guidelines for the evaluation and management of heart failure. Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee on Evaluation and Management of Heart Failure). J Am Coll Cardiol. 1995;26:1376-98.
  5. O'Connell JB, Bristow MR. Economic impact of heart failure in the United States: time for a different approach. J Heart Lung Transplant. 1994;13:S107-12.


Protocol Diagram

1. Patient presents with complaints consistent with heart failure
  
2. Review medical and medication history, physical exam, lab tests, ECG, X-rays, and other pertinent tests.
3. Does patient have symptoms that warrant hospitalization?

No
  
Yes		 4. Refer patient to the hospital. Exit protocol.
5. Determine NYHA functional class. Attempt to define the etiology of the heart failure and precipitating cause(s).
  
6. Does patient have ventricular systolic dysfunction?

Yes
  
No		 7. Refer patient to a cardiologist for further evaluation and treatment.
8. Begin patient and family education and counseling. Have patient begin lifestyle modifications. Discuss pharmacologic treatment strategies and goals.
  
9. Does patient have a significant
contraindication to
ACEI therapy?

No
  
Yes		 10. Initiate therapy with isosorbide dinitrate
and hydralazine (ISDN/HYD)		  
 Go to Box 12.
11. Initiate and titrate ACEI therapy over 1 to 4 weeks.

Go to Box 12.
  

Protocol Diagram- continued

From Boxes 10 and 11
  
12. Has patient developed any ADRs?



No





 
Yes		 13. Is the reaction severe?

Yes
  
No		 14. Treat ADR. Continue therapy. Reevaluate in 1 week.  
 Go to Box 16.
 

15. Discontinue therapy. If original therapy was ACEI, go to Box 10. If original therapy was ISDN/HYD, consider initiating another vasodilator or proceed to Box 16.  
16. Does the patient have signs or symptoms of volume overload?


No
  
Yes		 17. Initiate and titrate diuretic therapy.
 		 18. Are symptoms resolved?


No



 
Yes		 Go to Box 19.
19. Continue current therapies. Monitor the patient routinely for symptom deterioration, development of ADRs, and continued adherence. If volume overload develops, go to Box 16.   20. Initiate and titrate combination diuretic therapy.

 
21. Are symptoms resolved?


No
  
Yes		 Go to box 19.
22. Initiate and titrate digoxin therapy.
  
23. Are symptoms resolved?


No
  
Yes		 Go to box 19.
24. Consider initiating a ß-blocker and/or spironolactone.
  
25. Are symptoms resolved?


No
  
Yes		 Go to box 19.
26. Refer the patient to a specialist for further evaluation and comanagement.  
This protocol is a tool designed to help health professionals make decisions related to patient therapy. It is not intended to replace professional judgement or to establish the only approach to a problem.

©2001, American Pharmaceutical Association



Boxes 1 - 5

Box 1

A patient presents with complaints consistent with heart failure. When clinical heart failure develops, dyspnea on exertion (DOE) appears to be the earliest symptom. The presence of progressive DOE, paroxysmal nocturnal dyspnea (PND), or orthopnea warrants evaluation for heart failure (see Table 1). Other signs and symptoms in isolation are less likely to be a result of heart failure. However, heart failure must be considered if compatible signs and symptoms exist in conjunction with a history of heart disease, hypertension, or previous myocardial infarction.[1-9]

Box 2

Review results from the initial evaluation, which usually includes a physical examination, the patient's medical and medication histories, a chest X-ray, an electrocardiogram (ECG), a complete blood count, a complete chemistry panel (i.e., CHEM-24), a urinalysis, echocardiography or radionuclide ventriculography (RNV), and thyroid function tests. Echocardiography or RNV can distinguish between systolic and diastolic dysfunction primarily by determining left ventricular ejection fraction (LVEF). LVEF < 40% is conventionally defined as systolic dysfunction. The ECG is usually nonspecific, but it may help in identifying other underlying cardiovascular disease. The remaining tests provide information about potential precipitating, complicating, or primary causative factors.[1-4]

Physical examination findings are not highly sensitive indicators of heart failure. The most sensitive/specific physical finding is a third heart sound (i.e., S3 gallop). A chest X-ray that shows cardiomegaly and evidence of pulmonary congestion in a symptomatic patient is highly suggestive of heart failure. Some patients may have underlying left ventricular dysfunction as a result of insult to the myocardium, but they will not present with clinical evidence of heart failure.

Boxes 3 and 4

Does the patient present with signs or symptoms that require acute care? Patients should be referred for hospitalization if they have any of the following:[1] If the patient has any of the above signs or symptoms, exit the protocol. If not, continue to Box 5.

Box 5

Symptoms of heart failure have been grouped into a classification system based on a patient's ability to perform daily activities (see Table 2). This classification system, known as the New York Heart Association's (NYHA) Functional Classification, is the accepted standard for grading disease severity and for monitoring treatment efficacy and disease progression.

Once a diagnosis of heart failure has been confirmed, prepare a description of the heart failure. Pertinent information includes the form of heart failure (i.e., systolic versus diastolic); the etiology of the heart failure, including primary etiology and precipitating causes; and the patient's functional class.[1-4,7-9]

Boxes 6 - 10

Boxes 6 and 7

Does the patient have systolic ventricular dysfunction (i.e., ejection fraction < 40%) as determined by echocardiography or RNV? If yes, go to Box 8.

If no, refer the patient to a cardiologist for further evaluation and treatment.

Box 8

Begin patient and family education and counseling. The patient and family members must understand the disease and its effect on their lives. The basic pathophysiology and etiology of heart failure should be discussed. Patients should be educated about the expected signs and symptoms that indicate worsening heart failure (e.g., progressive DOE, sudden development of PND, weight gain, or orthopnea), prognosis and outcomes associated with heart failure, and signs and symptoms that should alert the patient to contact the physician (e.g., a 2-pound weight gain in 24 hours, severe DOE). Patient education should be an ongoing process.[1,10,11]

Lifestyle modifications must be immediately initiated and continually emphasized. It is very important to instruct the patient about his or her role in the management of the disease, including adherence to the treatment plan and avoidance of medications that can worsen symptoms (e.g., nonsteroidal anti-inflammatory drugs).[1,2,6,9-11] All patients should receive specific dietary guidelines, including sodium restriction (a critical strategy in the treatment of heart failure) and avoidance of excessive fluid intake. Tobacco use cessation, if applicable, and decreased alcohol consumption or abstinence, should be encouraged. Regular exercise (such as walking) as tolerated may improve the NYHA functional class. The importance of self-monitoring weight daily (to assess fluid retention) must be stressed in the education plan. Finally, it is necessary to complete assessments of the patient's ability to perform self-care and of the patient's support network.

When selecting pharmacotherapy for patients with heart failure, practitioners must consider the following goals: improvement in survival, alleviation of symptoms, improvement in exercise capacity, and prevention of treatment-associated hypotension and electrolyte disturbances. See Table 3 for common management mistakes. Comorbid conditions should be considered, because many heart failure patients will present with other concomitant medical problems. These conditions may aggravate heart failure and thus deserve intervention.

Box 9

Angiotensin-converting enzyme inhibitors (ACEIs) are the standard of care for systolic heart failure. An ACEI should be initiated unless the patient has a significant contraindication. Significant contraindications to the use of an ACEI include a history of severe adverse reactions during earlier exposure (e.g., angioedema or anuric renal failure) or during pregnancy. Caution should be used when prescribing an ACEI to patients with a serum potassium concentration > 5.5 mEq/L that cannot be reduced, symptomatic hypotension in the absence of volume contraction, serum creatinine levels > 3 mg/dL, or bilateral renal artery stenosis.[1,12,13] If contraindications exist, go to Box 10; in all other cases, proceed to Box 11.

Box 10

For patients who have a contraindication to an ACEI, initiate therapy with isosorbide dinitrate and hydralazine (ISDN/HYD).[1,13,14] Although ISDN/HYD therapy has been shown to reduce mortality in heart failure patients, it has not been approved by the Food and Drug Administration (FDA) because of significant adverse drug reactions (ADRs), including headache, palpitations, orthostatic hypotension, nausea, vomiting, diarrhea, peripheral neuritis, and nasal congestion.[15] Initiate doses as listed in Table 4 and titrate to target doses over 1 to 4 weeks.[1,13,16] It is important that patients maintain at least a 10-hour "nitrate-free" interval each day to avoid the development of nitrate tolerance.[6] For patients with heart failure, unlike those with angina, the nitrate-free interval should occur during the day, when dyspnea can be managed with diuretics; nitrates can be used at night to manage PND.

Monitor the patient for development of ADRs, a decrease in symptoms, and adherence. Adherence to a complicated medication regimen is difficult and requires significant training and support. Adverse effects occur frequently, but can often be managed without stopping therapy.[1,13,15]

Boxes 11 - 15

Box 11

Several large clinical trials have clearly documented that ACEIs reduce morbidity and mortality in patients with systolic heart failure; thus, ACEIs have become the cornerstone of heart failure therapy. Evidence suggests that ACEIs are useful in preventing the progression of heart failure in symptomatic patients.[5,6,13,16-22] All patients with symptomatic systolic heart failure should be treated with an ACEI unless a contraindication exists. Currently, many ACEIs are indicated for use in heart failure, with a mortality benefit seen in large clinical trials from captopril, enalapril, lisinopril, and ramipril when used at target doses.[23]

The intravascular volume status and renal function of a patient should be assessed before initiating an ACEI.[13] Patients at high risk for hypotension (e.g., those with volume contraction or hyponatremia) should receive the lowest recommended dose (e.g., lisinopril 2.5 to 5 mg daily). Doses of an ACEI should be titrated upward over 1 to 4 weeks to reach target doses (see Table 4). Patients should be examined 1 week after initiation of therapy. This examination should include measurement of serum potassium level, blood pressure, and serum creatinine, as well as an assessment of side effects. The full effect of these agents will not be apparent for several months.[1,3,13,14] To be effective in reducing mortality, ACEI therapy should be titrated to those doses shown to be effective in clinical trials.[5,6]

Boxes 12-15

Has the patient developed any ADRs during initiation and titration of therapy? If yes, go to Box 13. If no, go to Box 16. If there are no severe ADRs, treat the reaction and continue the current regimen titration.

Is the ADR severe (e.g., hypotension that is unresponsive to lowered dose[s], fluid retention, oropharyngeal angioedema)? If the patient had a severe ADR to ACEI therapy, discontinue the agent and go to Box 10 to begin ISDN/HYD therapy. If the severe reaction was to ISDN/HYD therapy, discontinue the treatment and consider switching to another vasodilator (e.g., felodipine). Reevaluate the patient in 1 week. Go to Box 16.

Boxes 16-20

Boxes 16 and 17

Evaluate the patient's fluid volume status (see Table 5). If the patient has no signs or symptoms of intravascular hypervolemia (volume overload), go to Box 19. If volume overload is indicated, initiate diuretic therapy (as in Table 4). Patients who exhibit signs or symptoms of volume overload have been shown to benefit from diuretic therapy, although the effects of such therapy on mortality are unknown.[1-3,5,6,9,10,12-14,17]

Diuretics commonly used include loop (e.g., furosemide) and thiazide (e.g., hydrochlorothiazide) compounds. Patients who require gradual diuresis or have mild symptoms may need only a thiazide diuretic. If the patient has a persistent volume overload despite the use of thiazides, severe volume overload, or decreased renal function (creatinine clearance < 30 mL/minute), a loop diuretic should be used. Titrate diuretics to a moderate diuresis, with therapeutic end points being improvement or resolution of symptoms and attainment of the desired target weight. Once these goals have been met, adjust the diuretic dose to maintain weight and diuresis goals. If greater diuresis is required, doubling the daily dose may result in a better response than will giving a smaller dose more frequently.

When initiating a diuretic concurrently with an ACEI or ISDN/HYD, it is important to avoid excessive diuresis, which may prevent upward titration of the other agents. If the patient has intravascular volume dehydration, titrate the diuretic dose slowly to prevent hypotension. Serum potassium levels and serum magnesium levels should be monitored until stable; during initiation, titration, or modification of a diuretic or other therapy; and periodically thereafter. Patients are to be monitored for signs of excessive diuresis. Potassium and magnesium supplementation must be individualized.[1,13]

Because diuretics are used to control symptoms of heart failure and have not been shown to decrease morbidity or mortality, these agents should not be used alone in the treatment of heart failure.

Box 18

Have the patient's heart failure symptoms resolved? If yes, go to Box 19. If no, go to Box 20.

Box 19

Continue current therapies and monitor for deterioration in symptoms and development of ADRs. Each visit should include a discussion of the importance of continued adherence to lifestyle modifications and drug therapy. When symptomatic exacerbation of heart failure occurs, return to Boxes 16 through 20 to maximize therapy.

Box 20

If heart failure symptoms are not improving after maximal diuretic titration, assess the patient's adherence to therapy. If intravascular fluid overload is still problematic with the use of a single diuretic, consider a combination of diuretics. By choosing diuretics with different mechanisms of action, combination therapy can result in larger increases of diuresis than can simply using larger doses of a single diuretic. Several diuretics are used in combination with loop diuretics, including spironolactone, thiazides, or metolazone.[24] Metolazone, unlike other thiazide diuretics, is particularly useful in patients with renal insufficiency because it maintains its effectiveness at glomerular filtration rates < 20 mL/minute. The combination of metolazone and a loop diuretic has been useful in the management of fluid overload in patients with congestive heart failure.[24]

Boxes 21-26

Boxes 21 and 22

Have the patient's symptoms resolved? If yes, go to Box 19. If no, consider adding digoxin to the regimen. Randomized, double-blind, placebo-controlled trials of digoxin in heart failure indicate that a significant proportion of patients will experience hemodynamic and clinical deterioration when digoxin is withdrawn, with or without an ACEI.[25-27] However, although these studies do not indicate which patients should initially be treated with digoxin, digoxin has emerged as the only inotropic agent that is not associated with increased mortality.[28] These studies do suggest that the patients who are most likely to benefit from digoxin are those at highest risk for clinical deterioration or those with markedly dilated ventricles, atrial fibrillation, and a third heart sound.[1,11-14,25,26,29] Patients with reduced renal function, elderly patients, or patients with baseline arterioventricular nodal conduction abnormalities may be started at 0.125 mg/day. A loading dose is usually not required.

Digoxin serum concentrations should be considered as a guide to aid in monitoring the response to digoxin therapy. Digoxin serum concentrations between 0.8 and 1 ng/mL are considered therapeutic; those > 2 ng/mL increase the risk for toxicity. Once the patient is receiving a stable dose of digoxin, it is reasonable to monitor levels yearly or when clinically indicated (i.e., when heart failure worsens, renal function deteriorates, toxicity is evident, or medications that may alter the concentration of digoxin are added).[1,13,21]

Digoxin should be discontinued or stopped temporarily if evidence of toxicity exists, renal function deteriorates, or serum concentrations are elevated. Renal function and electrolytes should be monitored regularly (i.e., every few months).[16,19-21]

Box 23

Have the patient's symptoms improved? If yes, continue current therapies and monitor for deterioration in symptoms and the development of ADRs. Each visit should include a discussion of the importance of continued adherence to lifestyle modifications and drug therapy. Go to Box 19 for additional drug therapy considerations. If symptoms have not improved or are not improving at an acceptable rate, go to Box 24.

Box 24

ß-blockers. Where ß-blocker use in heart failure was once contraindicated, in recent years it has become a first-line therapy. Although larger doses of ß-blockers can lead to symptomatic worsening in patients with heart failure, lower doses used in stable patients may result in significant benefit. Clinical trials have demonstrated an increase in ejection fraction,[30,31] global symptom improvement, decreased hospitalizations, decreased need for heart failure medications, and decreased mortality.[32,33] The benefit seen with ß-blockers has been attributed to a number of possible mechanisms, including their antiarrhythmic activity, decreasing sympathetic stimulation, and blocking the detrimental effects of sympathetic stimulation in heart failure patients.

Although many ß-blockers have been studied, only carvedilol, bisoprolol, and metoprolol have been shown in clinical trials to decrease morbidity and mortality in patients with heart failure. Currently, FDA has approved only carvedilol to treat mild or moderate NYHA Class II or III heart failure of ischemic or cardiomyopathic origin, in conjunction with digitalis, diuretics, and ACEIs. Carvedilol, a nonselective ß-blocker with alfa1-receptor blockade, was initially thought to be the best ß-blocker for heart failure because of its ancillary effects (vasodilation and decreased neurohormonal activation). However, data have shown that bisoprolol and metoprolol have effects similar to those of carvedilol in patients with heart failure.[33] Therefore, it seems likely that any ß-blocker without intrinsic sympathomimetic activity would be beneficial in the management of heart failure.

ß-blockers should be initiated at very low doses (carvedilol 3.125 mg twice daily, bisoprolol 1.25 mg once daily, or metoprolol SR 12.5 mg once daily) followed by a doubling in dose every 2 to 4 weeks as tolerated.[12] Patients must be monitored for evidence of hypotension, bradycardia, fluid retention, or worsening heart failure during the titration process. If any of these adverse effects occur, lower the dose until the effect resolves and then try to raise the dose again. It may take 2 to 3 months for clinical improvements to be seen. Even if there is no apparent improvement at maximally tolerated doses, long-term treatment should be maintained to decrease the risk of disease progression.

Spironolactone. Spironolactone, an aldosterone antagonist, has been studied in patients with advanced heart failure. In theory, aldosterone antagonists should aid in blocking the fluid retention caused by activation of the renin-angiotensin-aldosterone system. To date, spironolactone has only been evaluated in patients with ischemic or nonischemic cardiomyopathy and severe heart failure (recent or current NYHA Class IV). This study found that treatment with spironolactone was associated with a reduction in mortality and a decrease in hospitalizations for heart failure.[34] Spironolactone was well tolerated in most patients, except for the occurrence of gynecomastia in 8% to 9% of patients. According to this study, low doses of spironolactone (up to 25 mg/day) may be considered in patients with current or recent NYHA Class IV heart failure. The usefulness of spironolactone in patients with mild or moderate heart failure remains unknown.

Boxes 25 and 26

Are the patient's symptoms improved or improving? If yes, go to Box 19. If no, refer the patient to a specialist for further evaluation and comanagement.

Sidebar: Protocol Development Process

All of the protocols developed through APhA are subject to the following process:

Table 1. Signs and Symptoms Suggestive of Heart Failure

Paroxysmal nocturnal dyspnea

Orthopnea

Dyspnea on exertion

Lower extremity edema

Decreased exercise tolerance

Fatigue

Abdominal symptoms (e.g., nausea, abdominal pain)

Inspiratory crackles

Jugular venous distension

Cardiomegaly

Third heart sound


Table 2. New York Heart Association's Functional Classification of Congestive Heart Failure

Class Symptoms
I No symptoms associated with ordinary activity. Physical activity not limited.
II Asymptomatic at rest, but symptoms (dyspnea, fatigue, palpitations) occur with ordinary activity. Physical activity minimally limited.
III Asymptomatic at rest, but symptoms occur with less than ordinary activity. Physical activity markedly limited.
IV Symptoms at rest. Physical activity worsens symptoms.
Source: Reference 1.

Table 3. Common Mistakes in Management of Heart Failure

Improper dosage of diuretics

Failure to assess quality of life

Failure to consider long-term therapeutic goals

Inadequate doses of angiotensin-converting enzyme inhibitors (ACEIs)

Failure to use isosorbide dinitrate and hydralazine in patients with a contraindication for ACEI therapy

Use of medications known to precipitate heart failure symptoms

Failure to optimize lifestyle modifications
Source: Reference 5.

Table 4. Medications Used to Treat Heart Failure

Medication Initial Dose Target Dose Maximal Dose Side Effects
Diuretics
Hydrochlorothiazide 25 mg every day As needed 50 mg every day Postural hypotension, hypokalemia, hyperkalemia, hyperglycemia, hyperuricemia, hypomagnesemia, gynecomastia (spironolactone only), rash
Chlorthalidone 25 mg every day As needed 50 mg every day
Furosemide 10-40 mg every day As needed 240 mg twice a day
Bumetanide 0.5-1.0 mg every day As needed 10 mg every day
Ethacrynic acid 50 mg every day As needed 200 mg twice a day
Torsemide 5-10 mg every day As needed 200 mg every day  
Metolazone 2.5 mg every day As needed 10 mg every day
Spironolactone 25 mg every day As needed 100 mg twice a day
Amiloride 5 mg every day As needed 40 mg every day
Triamterene 50 mg every day As needed 100 mg twice a day
Angiotensin-converting enzyme inhibitors
Captopril 6.25-12.5 mg three times a day 50 mg three times a day 50 mg three times a day Hypotension, hyperkalemia, cough, skin rash, renal failure, angioedema, neutropenia
Enalapril 1.25-2.5 mg twice a day 10 mg twice a day 20 mg twice a day
Fosinopril 5-10 mg every day 20 mg every day 40 mg every day  
Lisinopril 2.5-5.0 mg every day 20 mg every day 40 mg every day
Ramipril 1.25-2.5 mg twice a day 5 mg twice a day 5 mg twice a day
Quinapril 5-10 mg twice a day 20 mg twice a day 20 mg twice a day
Digoxin 0.125-0.25 mg every day 0.125-0.25 mg every day 0.375 mg and based on response Arrhythmias, confusion, nausea anorexia, visual disturbances
Hydralazine 10 mg four times a day times a day 75 mg four Not applicable Headache, nausea, dizziness, tachycardia, lupus-like syndrome
Isosorbide dinitrate 5-10 mg three times a day 40 mg three times a day 80 mg three times a day Headache, hypotension, flushing
Source: Reference 5.

Table 5. Signs and Symptoms of Volume Overload

Signs
Peripheral edema

Jugular venous distension

Hepatojugular reflex

Hepatomegaly

Pleural effusion

Inspiratory crackles
Symptoms
Anorexia

Dyspnea on exertion

Orthopnea

Nocturia

Exercise intolerance


References

  1. Agency for Health Care Policy and Research. Heart Failure: Evaluation and Care of Patients with Left-Ventricular Systolic Dysfunction. Rockville, Md: U.S. Department of Health and Human Services; 1994. Clinical Practice Guideline 11. AHCPR publication 94-0612.
  2. Klamerus KJ. Current concepts in clinical therapeutics: congestive heart failure. Clin Pharm. 1986;5:481-98.
  3. Johnson JA, Lalonde RL. Congestive heart failure. In: DiPiro JT, Talbert RL, Hayes PE, et al., eds. Pharmacotherapy: A Pathophysiologic Approach. 2nd ed. New York, NY: Elsevier Science; 1992:160-93.
  4. Braunwald E. Clinical manifestations of heart failure. In: Braunwald E, ed. Heart Disease. A Textbook of Cardiovascular Medicine. 3rd ed. Philadelphia, Pa: W.B. Saunders Company; 1988:471-84.
  5. Cohn JN. The management of chronic heart failure. N Engl J Med. 1996;335:490-8.
  6. Guidelines for the evaluation and management of heart failure. Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee on Evaluation and Management of Heart Failure). J Am Coll Cardiol. 1995;26:1376-98.
  7. Patterson JH, Adams KF. Pathophysiology of heart failure. Pharmacotherapy. 1993;13(5 pt 2):73S-81S.
  8. Packer M. Pathophysiology of chronic heart failure. Lancet. 1992;340:88-91.
  9. Parker RB. Teaching congestive heart failure to doctor of pharmacy students. Am J Pharm Ed. 1992;56:179-85.
  10. Dracup K, Baker DW, Dunbar SB, et al. Management of heart failure. II. Counseling, education and lifestyle modifications. JAMA. 1994;272:1442-6.
  11. Armstrong PW, Moe GW. Medical advances in the treatment of congestive heart failure. Circulation. 1993;88:2941-52.
  12. Consensus recommendations for the management of chronic heart failure. On behalf of the Advisory Council to Improve Outcomes Nationwide in Heart Failure. Am J Cardiol. 1999;83(2A):1A-38A.
  13. Baker DW, Konstam MA, Bottorff M, et al. Management of heart failure. I. Pharmacologic treatment. JAMA. 1994;272:1361-6.
  14. Weintraub NL, Chaitman B. Newer concepts in the medical management of patients with congestive heart failure. Clin Cardiol. 1993;16:380-90.
  15. Cohn JN, Archibald DG, Ziesche S, et al. Effect of vasodilator therapy on mortality in chronic congestive heart failure. Results of a Veterans Administration Cooperative Study. N Engl J Med. 1986;314:1547-52.
  16. 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. 1991;325:303-10.
  17. Chow MS. Assessing the treatment of congestive heart failure: diuretics, vasodilators, and angiotensin-converting enzyme inhibitors. Pharmacotherapy. 1993;13(5 pt 2):82S-7S.
  18. Effects of enalapril on mortality in severe congestive heart failure. Results of the Cooperative North Scandinavian Enalapril Survival Study (CONSENSUS). The Consensus Trial Study Group. N Engl J Med. 1987;316:1429-35.
  19. Effect of enalapril on survival in patients with reduced left ventricular ejection fractions and congestive heart failure. The SOLVD Investigators. N Engl J Med. 1991;325:293-302.
  20. Effect of enalapril on mortality and the development of heart failure in asymptomatic patients with reduced left ventricular ejection fractions. The SOLVD Investigators. N Engl J Med. 1992;327:685-91.
  21. Effect of captopril on mortality and morbidity in patients with left ventricular dysfunction after myocardial infarction. Results of the survival and ventricular enlargement trial. The SAVE Investigators. N Engl J Med. 1992;327:669-77.
  22. Groden DL. Vasodilator therapy for congestive heart failure. Lessons from mortality trials. Arch Intern Med. 1993;153:445-54.
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Appendix

American Pharmaceutical Association Management of Chronic Systolic Heart Failure Protocol Participants

Section Editor Comprehensive Protocol Reviewer
James Karboski, PharmD
Lecturer
Division of Pharmacy Practice
   and Administration
College of Pharmacy
University of Texas -- Austin
Austin, Tex.		 Stephanie Garrett, PharmD
Assistant Professor
Health Sciences Division
College of Pharmacy
Nova Southeastern University
Ft. Lauderdale, Fla.


Daniel H. Albrant, PharmD, is editor in chief, APhA Drug Treatment Protocols Project.


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