Overview of Heart Failure Pharmacotherapy

Heart failure (HF) is estimated to cost Americans $30.7 billion each year, 68% of which is in direct costs and 32% in indirect ones, according to the American Heart Association (AHA).¹

In 2009, HF was a contributing factor in 1 of 9 deaths in the United States.

Pathophysiology

HF is often characterized by decreased diastolic and systolic dysfunction.² Diastolic dysfunction can arise from mitral/tricuspid valve stenosis, myocardial ischemia, pericardial disease, and ventricular hypertrophy. Systolic dysfunction can be caused by dilated cardiomyopathy, reduced muscle mass, and ventricular hypertrophy. HF results in decreased cardiac output, leading to compensatory responses such as Frank—Starling mechanism, remodeling, tachycardia through sympathetic nervous system activation, and vasoconstriction.

Pharmacotherapy

Both the American College of Cardiology Foundation (ACCF)/AHA and the New York Heart Association (NYHA) stage HF by functional classification, though with different focuses.³ The ACCF/AHA uses disease progression, and the NYHA employs exercise capacity and symptomatic status. For a look at the ACCF/AHA staging and the suggestions for drug therapy, see the Table.

Stage A

The ACCF/AHA recommends treating for comorbid conditions such as dyslipidemia and hypertension.³ Guidelines such as those from the ACCF/AHA and the Eighth Joint National Committee may be used for this purpose.

Stage B

The American College of Cardiology (ACC)/AHA recommend that angiotensin-converting enzyme (ACE) inhibitors or angiotensin receptor blockers (ARBs) for patients showing intolerance to ACE inhibitors be used with reduced ejection fraction (EF), regardless of the history of acute coronary syndrome (ACS) or myocardial infarction (MI).³ ACE inhibitors and ARBs provide not only mortality benefits but also symptomatic management.

For patients with a history of ACS or MI with reduced EF, beta-blockers, such as bisoprolol, carvedilol, and metoprolol succinate, may be considered to provide a mortality benefit. Regardless of EF, statin therapy can prevent symptomatic HF and cardiovascular events for individuals with a history of ACS or MI.

Stage C

The 2017 ACC/AHA/HFSA Focused Update of the 2013 ACCF/AHA Guideline for the Management of Heart Failure recommends prescribing ACE inhibitors, ARBs, or angiotensin receptor—neprilysin inhibitors (ARNIs) with a beta-blocker for reduced EF.⁴ ARNIs should not be administered to patients with a history of angioedema.

The ACCF/AHA recommends replacing an ACE inhibitor or an ARB with an ARNI for NYHA class II or III because an ARNI provides superior benefits in mortality compared with an ACEI. Ivabradine may be considered for symptomatic patients with stable chronic HF with reduced EF who are receiving the maximum tolerated dose of a beta-blocker (sinus rhythm, heart rate 70 beats per minute or greater at rest). Ivabradine has been shown to reduce hospitalization.

For patients with preserved EF, diuretics must be used for symptomatic management because of volume overload. However, if a patient has EF ≥45%, elevated brain natriuretic peptide levels, or HF admission within 1 year, with an estimated glomerular filtration rate >30 mL/min, creatinine <2.5 mg/dL, a potassium concentration of <5.0 mEq/L, aldosterone receptor antagonists can be considered to reduce hospitalization.

Stage D

Use of intravenous inotropic agents is reasonable for HF refractory to guideline-directed medical therapy and eligibibilityto receive cardiac transplantation or mechanical circulatory support (MCS).³ Long-term use of inotropic agents is considered palliative for those who are not eligible to receive cardiac transplantation or MCS.

Pharmacists’ Role in HF Therapy

Pharmacists’ role should not be limited to evaluating the appropriateness of drug therapy and educating patients with HF. As experts in pharmacotherapy, pharmacists are encouraged to guide doctors, nurse practitioners, physicians’ assistants, and other health care professionals to optimize pharmacotherapy.

David Kim, PharmD, is a pharmacy specialist in the US Army Reserve.

References

• Writing Group Members, Mozzafarian D, Benjamin EJ, et al; American Heart Association Statistics Committee, Stroke Statistics Subcommittee. Heart disease and stroke statistics-2016 update: a report from the American Heart Association. Circulation. 2016;133(4):e38-e360. doi: 10.1161/CIR.0000000000000350.
• Heart failure. In: Wells BG, DiPiro JT, Schwinghammer TL, DiPiro CV, eds. Pharmacotherapy Quick Guide. New York, NY: McGraw-Hill.2017.
• ACCF/AHA Task Force on Practice Guidelines. 2013 ACCF/AHA guideline for the management of heart failure. circ.ahajournals.org/content/early/2013/06/03/CIR.0b013e31829e8776. Published June 5, 2013. Accessed May 20, 2018.
• ACCF/AHA Task Force on Practice Guidelines. 2017 ACC/AHA/HFSA focused update of the 2013 ACCF/AHA guideline for the management of heart failure. circ.ahajournals.org/content/early/2017/04/26/CIR.0000000000000509. Published April 28, 2017. Accessed May 21, 2018