Many medications used for HF improve symptoms, but have not proven to have any effect on mortality. Diuretics have been shown to improve symptoms, but there is limited data on the long- term benefits and mortality (Faris et al., 2006; Hobbs & Boyle, 2010). According to CHF guidelines published by the Heart Failure Society of America, diuretics are first-line therapy in the treatment of CHF (Congestive Heart Failure) (Colucci, 2009). A meta-analysis by Faris et al. (2006) reviewed 14 clinical trials that revealed that participants who were treated with diuretics had reduced read- mission rates (OR = 0.7, P = .01, in 2 clinical trials) and improvement of exercise capacity (OR = 0.72, P , .001, in 4 trials); the participants in the control group were treated with placebo.
The accumulation of fluid/extra volume in HF patients causes shortness of breath; diuretics can relieve these symptoms more quickly than any other medication for HF. The most common type of diuretics used for decompensated HF are loop diuretics; however, thiazide diuretics may also be added for patients with resistant symptoms (Faris et al., 2006; Hobbs & Boyle, 2010;
Sterns & Colucci, 2010). Decompensated HF patients may require hospitalization and IV diuret- ics owing to symptoms related to mucosal edema and decreased intestinal perfusion. Once the patient’s HF is compensated, they may be changed to oral diuretics. The effective dose of diuretics in patients with HF is higher than in patients without HF (Brater, 2000).
Although diuretics are used daily for the treatment of HF and considered a mainstay of treat- ment, they are not without concerns. Orthostatic hypotension, hypokalemia, metabolic alkalosis, elevation of neurohormone levels, cardiorenal syndrome, resistance to therapy, and worsening renal
function can occur (Hobbs & Boyle, 2010; Sterns & Colucci, 2010). Owing to these potential side effects, the importance of regular monitoring of labs such as a basic metabolic panel is imperative.
Nitrates are another medication that can be used for symptom relief of HF. The most ben- eficial use of nitrates is when added to diuretics. Nitroglycerine is the most commonly used ni- trate. Nitroglycerine causes venodilation and thus decreases LV filling pressure (Colucci, 2011).
The most common side effects of this medication are hypotension and headache. Although the use of nitrate alone has not shown any reduction in mortality, the use of nitrates plus hy- dralazine provides symptomatic relief and reduces mortality benefit in selected patients with systolic HF.
The use of hydralazine plus oral nitrate therapy is recommended for patients with persistent NYHA class III to IV HF and LVEF less than 40% and/or those who exhibit contraindications to ACE inhibitors and ARBs owing to renal insufficiency (Colucci, 2009; Falvey & Blaxall, 2009).
Nitrates should be avoided within 24 hours of a patient’s use of the phosphodiesterase inhibi- tors. In addition, the clinician should consider holding nitrates if systolic blood pressure is less than 90 mm Hg to avoid syncope. Finally, it is important to note that nitrate tolerance can occur (Colucci, 2011).
Digoxin has been used for over 200 years in the treatment of HF. However, there is no litera- ture to suggest that it improves survival. Digoxin can be beneficial in patients with systolic HF and has shown a decrease in the rate of admission for these patients. Digoxin is recommended for
Table 4.2 • Classification of Heart Failure Stages
Stage Incidence in the
United States Symptoms Findings Goal of Treatment
Stage A 60 million Patients at risk for develop- ing HF includes patients with diabetes mellitus, hyperten- sion, cardiotoxin exposure, history of rheumatic fever, and hemochromatosis
No structural heart disease The goal is to decrease the risk of progression
Stage B 32.6 million Asymptomatic heart disease Decreased LV ejection fraction, LVH, regional wall motion abnormality, or valve disorder
The goal is prevention of LV remodeling
Stage C 6.2 million Symptomatic HF Structural heart disease, dyspnea, fatigue, and im- paired exercise tolerance
The goal is medication adjustment to help with symptoms. CRT also may be considered
Stage D 200,000 Severe refractory HF End-of-life care or high- technology therapies such as cardiac transplantation or mechanical circulatory support, based on indi- vidual cases
The goal is symptom management
From the ACC/AHA classification of chronic heart failure, Hunt, S. A., Abraham, W. T., Chin, M. H., Feldman, A. M., Francis, G. S., Ganiats, T. G., . . . Yancy, C. W.
(2009). 2009 focused update incorporated into the American College of Cardiology/American Heart Association 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. Circulation, 119(14), e391–e479.
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patients with EF less than 40% and who continue to have NYHA functional class II, III, and IV symptoms even with optimal therapy. Literature suggests that maintaining digoxin levels between 0.5 and 0.8 ng/ml in both men and women will decrease the likelihood of toxicity. Bradycardia, anorexia, nausea, and dizziness can be seen in patients who have digoxin toxicity (Colucci, 2009).
ACE inhibitors are considered the cornerstone of HF therapy related to systolic dysfunction and post-MI (Gring & Francis, 2004). ACE inhibitors have been shown to decrease mortality and promote remodeling (Gring & Francis, 2004; Strippol et al., 2004). A meta-analysis by Shekelle et al. (2003) of six different studies of ACE inhibitors found that patients with LV systolic dys- function have a reduced rate of all-cause mortality when ACE inhibitors are used. Thus, ACE inhibitors are the most important antagonist of the RAAS and are prescribed routinely in patients with HF and reduced LV systolic function (Gring & Francis, 2004).
ARBs have different validations for use. Often they are prescribed in patients who are already on ACE inhibitors owing to the phenomenon of ACE-escape, which results in steady increase of the serum angiotensin II and aldosterone levels, even though ACE inhibitors are being used to cause RAAS inhibition. Other reasons for the use of ARBs are for more specific angiotensin II blockade, preservation of unopposed angiotensin II agonism, and for patients who cannot take ACE owing to allergy or intolerance (Gring & Francis, 2004).
ACE inhibitors and ARBs have been proven to delay the progression of diabetic nephropathy (Strippoli et al., 2004). They also have potential side effects that include hyperkalemia, especially in patients 75 years and older, usually as a result of renal dysfunction (Strippoli et al., 2004). As mentioned earlier, a dry cough may develop in up to 25% of patients who take ACE inhibitors (Simon et al., 1992). Two uncommon side effects but that need to to be kept in mind with ACE inhibitors are angioedema and acute renal failure (caused by bilateral renal artery stenosis); both require discontinuation of the drug (Hobbs & Boyle, 2010).
Statins have been shown to have benefits in patients with HF regardless of atherosclerosis or lipid levels. They have pleiotropic effects that include inhibition of inflammatory cytokines, improvement in endothelial function, repair of damaged autonomic function, potentiation of nitric oxide synthesis, and reversal of myocardial remodeling (Horwich et al., 2004). The most common side effect of statins is myopathy (Sinzinger et al., 2002). In addition, 0.5% to 2.0% of pa- tients on statin have elevated hepatic transaminases. Both side adverse effects are dose-dependent (Cleeman et al., 2002). Baseline liver function test should be obtained before initiation of statin therapy and then again every 3 months to ensure there is no increase in hepatic transaminase levels (Murphy, 2011). For patients who complain of myalgias or myopathy, a total creatine kinase can be drawn, and if elevated, statin use may need to be reconsidered. Finally, the clinician should be on the lookout for drug-to-drug interactions when prescribing statins (Sinzinger et al., 2002).
Aldosterone agonists prevent sodium and water retention, endothelial dysfunction, and myo- cardial fibrosis. Spironolactone and eplerenone are two aldosterone agonists that are approved for HF. Spironolactone has a 30% decrease in hospitalization and mortality when added to stan- dard therapy in patients with NYHA class III or IV and a serum creatine less than 2.5. Eplere- none has shown a 15% decrease in hospitalization and risk of death in patients with HF after an MI and EF less than 40%. A potential side effect of these medications is hyperkalemia, so these medications should be avoided in patients with creatinine greater than 2.5. Also, gynecomastia is reported in 8% of patients who take spironolactone, and hirsutism is a potential side effect (Hobbs & Boyle, 2010).
Beta-blockers improve survival in patients with HF, although the precise mechanism of ac- tion is unknown. It is suspected to be due to one or more of antiarrhythmic, antiremodeling,
anti-ischemic, and antiapoptotic properties, a decrease in heart rate, and a decrease in myocardial oxygen consumption. Potential side effects include severe bronchospasm, hypotension, bradycar- dia, fatigue, worsening depression, and potentially increase blood glucose (Hobbs & Boyle, 2010).
Inotropes that are used in the treatment of acute decompensated HF are divided into two types: beta-adrenergic agonists and phosphodiesterase-III inhibitors. These are IV medications most often administered in the hospital setting. Each type works differently, but the overall goal is to temporarily improve heart function and cardiac output, thus temporarily improving the pa- tient’s symptoms from HF. Inotropes have a risk of irregular heart rhythm and increased demand for oxygen by the heart. These medications should only be used in severe cases of symptomatic HF with evident hypoperfusion (Peterson & Felker, 2008).
Vasopressin antagonists cause arterial and venous vasodilation, thus leading to an increase in cardiac output through afterload reduction. Vasopressin antagonists are IV medications, and the dose is calculated by weight and is used for patients with acute decompensated HF (Hobbs
& Boyle, 2010). Natrecor was a popular drug in this class of medications for use in HF in 2004.
However, in 2006, questions arose about its safety in renal patients and was found to have a high rate of mortality in these patients. Although natrecor is still in use, it has been recommended that more studies need to be conducted regarding the safety and efficacy of this medication (Kesselheim et al., 2006). There are other vasopressin antagonists that may be considered if a patient with acute decompensated HF cannot get symptom relief with IV loop diuretics.