Drugs used to treat of heart failure with reduced ejection fraction
- *Corresponding Author:
- Emmanuel Teryila Tyokumbur
Department of Zoology, University of Ibadan
Ibadan, Oyo Nigeria, Nigeria
E-mail: [email protected]
Accepted: December 28, 2016
Citation: Leonardo R, Elmiro S R, Anaisa S R B, Giuseppe B Z. Drugs used to treat of heart failure with reduced ejection fraction. Curr Trend Cardiol. 2017;1(1):8-11.
Heart failure patients need multiple medications to treats a different symptom or contributing factor. Individuals diagnosed with heart failure typically take 5 or more different medications daily. Treatment may help live longer and reduce your chance of dying suddenly. This review describes the main drugs used to treat heart failure with reduced ejection fraction.
Heart failure, Drugs, Treatment.
Heart failure (HF) is the common final pathway of most diseases that affect the heart, being one of the most important current clinical challenges in health. HF is characterized by intolerance to exercise, fluid retention and congestive phenomena, and in its later stages has high morbidity and mortality rates. These patients those with preserved systolic function, are referred to as heart failure with preserved ejection fraction (HFpEF). HF is associated with left ventricular dysfunction, and in symptomatic patients with left ventricular ejection fraction (LVEF) ≤ 40%, this condition is called heart failure with reduced ejection fraction (HFrEF) or systolic heart failure. In this brief review we will focus on drug treatment of HFrEF (Table 1) [1-7].
|Drugs for Chronic HFrEF|
|Drug||Initial(I) and maximum(M) dose in adults|
|Angiotensin-Converting Enzyme (ACE) Inhibitors||Adverse Effects (AE): Cough, angioedema, hypotension, renal insufficiency, hyperkalemia, rash, taste disturbances, and neutropenia.|
|Enalapril**||2.5 mg||20 mg|
|Captopril***||6.25 mg||50 mg|
|Lisinopril*||2.5-5 mg||40 mg|
|Perindopril*||2 mg||16 mg|
|Fosinopril*||5-10 mg||40 mg|
|Ramipril*||1.25-2.5 mg||10 mg|
|Trandolapril*||1 mg||4 mg|
|Quinapril**||5 mg||20 mg|
|Digitalis Glycoside||AE: Conduction disturbances, cardiac arrhythmias, nausea, vomiting, confusion, and visual disturbances.|
|Digoxin *||0.125 mg||0.125-0.25mg or once every other day|
|Vasodilators||AE: Tachycardia, peripheral neuritis, lupus-like syndrome, headache and dizziness.|
|Isosorbiddinitrate/hydralazine***||20 mg/37.5 mg||40 mg/75 mg|
|Aldosterone Antagonists||AE: Hyperkalemia, renal impairment, erectile dysfunction, painful gynecomastia and menstrual irregularities|
|Spironolactone*or**||12.5-25 mg||25 mg|
|Eplerenone*||25 mg||50 mg|
|Diuretics||AE: hypokalemia, worsening of renal function, gout, hypomagnesemia and renal insufficiency.|
|Furosemide *or**||20-40 mg||600 mg|
|Bumetanide*or**||0.5-1 mg||10 mg|
|Torsemide*or**||10-20 mg||200 mg|
|Beta-Adrenergic Blockers (BB)||AE: Fatigue, hypotension, bradycardia, asymptomatic fluid retention, dizziness, headache, nausea, stomach pain, trouble sleeping.|
|Metoprolol succinate*||12.5-25 mg||200 mg|
|Bisoprolol*||1.25 mg||10 mg|
|Carvedilol**||3.125 mg||25 mg/(50 mg for pts>85 kg)|
|Angiotensin Receptor Blockers (ARBs)||AE: Angioedema, hypotension, renal insufficiency, and hyperkalemia.
ARBs: Can be used in patients who cannot tolerate an ACE Inhibitor mainly due to coughing
|Losartan*||25-50 mg||150 mg|
|Valsartan**||20-40 mg||160 mg|
|Candesartan cilexetil*||4-8 mg||32 mg|
|Azilsartanmedoxomil*||40-80 mg||80 mg|
|Once a day *; bid - Twice a day**; tid- Three times a day***; pts- Patient; HFrEF - Heart Failure with reduced Ejection Fraction.|
Table 1: Drugs for Chronic HFrEF.
Angiotensin-Converting Enzyme (ACE)
All patients with HFrEF should receive ACE inhibitors. It is seen an improved in symptoms between 4-12 weeks, as well as reducing the incidence of hospitalization, and increased patient survival. Blood pressure, renal function and serum potassium levels should be monitored, and also must be used with caution in patients with stenosis bilateral renal artery systolic blood pressure <80 mmHg, serum creatinine >3 mg/dl the serum potassium >5.0 mEq/L. They are contraindicated in patients with a history of angioedema and pregnancy [8,9].
Digoxin can reduce the rate of hospitalization and heart failure symptoms, increase exercise tolerance, but has no results on the survival rate. Doses are adjusted according to renal function, age and concomitant medications [10-13].
It could be beneficial in patients intolerant of an ACE inhibitor or an ARB or those that need additional control of blood pressure, despite the maximum standard dose therapy. It should not be used in conjunction with sildenafil because of the risk of hypotension [2,8].
Aldosterone Antagonists (AA)
It is recommended for patients with heart failure NYHA class II-IV with an LVEF ≤ 35%, and has been shown to reduce the risk of hospitalization and death. Renal function and serum creatinine concentrations should be monitored during treatment. AA should be avoided in patients with serum potassium >5.0 mEq/L and in those with reduced renal function (baseline serum creatinine >2.0 mg/dl for women or >2.5 mg/dl for men, or an estimated GFR [2,8,14,15].
Most patients with heart failure have fluid retention. Diuretics in such patients may alleviate pulmonary and peripheral symptoms, but its effect on survival is controversial. Diuretics (furosemide or bumetanide) acting on the loop of Henle, are more effective for the treatment of heart failure than thiazide diuretics (furosemide, bumetanide), acting on the distal tubule [2,8,16,17].
Beta-Adrenergic Blockers (BB)
Its combination with an ACE inhibitor consistently leads to a 30-40% reduction in hospitalization and mortality in adults with heart failure class III-IV (NYHA) class. Should be started at low doses and its increase is gradual, usually at 2-week intervals until the maximum tolerated dose [2,8,18-22].
Angiotensin Receptor Blockers (ARBs)
Therapy with an ARB reduces the risk of death in patients with HFrEF; and can be used in patients who cannot tolerate mainly due to coughing an ACE inhibitor. Blood pressure, renal function, and serum potassium concentrations should be monitored [2,8,23].
Serelaxin is a recombinant human relaxin-2 vasoactive peptide that causes systemic and renal vasodilation. The clinical benefits may including improving systemic, cardiac, and renal hemodynamics, and protecting cells and organs from damage via neurohormonal, anti-remodeling, anti-fibrotic, anti-ischemic, anti-inflammatory, and pro-angiogenic effects [24-26].
Recent studies with the novel agent LCZ696, a dual-acting angiotensin receptor blocker and neprilysin inhibitor (ARNi), with the well stablished ACE inhibitor enalapril and found significant reduction in mortality among the chronic HFrEF [27-32].
The main combinations of the medications used in treating heart failure are shown in Figure 1.
Drugs used to HFrEF can reduce the rate of hospitalization and heart failure symptoms, increase exercise tolerance and patient survival.
- Zachariah D, Taylor J, Rowell N, Spooner C, Kalra PR. Drug therapy for heart failure in older patients-what do they want? J GeriatrCardiol 2015; 12: 165-173.
- Yancy CW, Jessup M, Bozkurt B, Butler J, Casey Jr DE, Drazner MH, Fonarow GC, Geraci SA, Horwich T, Januzzi JL, Johnson MR, Kasper EK, Levy WC, Masoudi FA, McBride PE, McMurray JJ, Mitchell JE, Peterson PN, Riegel B, Sam F, Stevenson LW, Tang WH, Tsai EJ, Wilkoff BL. 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. J Am CollCardiol 2013; 128:e240.
- Barón-Esquivias G, Manito N, LópezDíaz J, Martín Santana A, GarcíaPinilla JM, Gómez Doblas JJ, Gómez Bueno M, Barrios Alonso V, Lambert JL. Update for 2014 on clinical cardiology, geriatric cardiology, and heart failure and transplantation. Rev EspCardiol 2015; 68: 317-323.
- Lindenfeld J, Albert NM, Boehmer JP, Collins SP, Ezekowitz JA, Givertz MM, Katz SD, Klapholz M, Moser DK, Rogers JG, Starling RC, Stevenson WG, Tang WH, Teerlink JR, Walsh MN. HFSA 2010 Comprehensive Heart Failure Practice Guideline. J Card Fail 2010; 16: e1-194.
- Drugs for chronic heart failure. JAMA 2015; 313: 1052-1053.
- Sato Y. Multidisciplinary management of heart failure just beginning in Japan. J Cardiol 2015; 66: 181-188.
- Kaldara E, Sanoudou D, Adamopoulos S, Nanas JN. Outpatient management of chronic heart failure. Expert OpinPharmacother 2015; 16: 17-41.
- Armstrong C. ACCF and AHA Release Guidelines on the Management of Heart Failure. Am Fam Physician 2014; 90: 186-189.
- Reed BN, Sueta CA. Stage B: what is the evidence for treatment of asymptomatic left ventricular dysfunction? CurrCardiol Rev 2015; 11: 18-22.
- Chaggar PS, Shaw SM, Williams SG. Is foxglove effective in heart failure? CardiovascTher 2015; 33: 236-241.
- Vamos M, Erath JW, Hohnloser SH. Digoxin-associated mortality: a systematic review and meta-analysis of the literature. Eur Heart J 2015; 36: 1831-1838.
- Al-Zakwani I, Panduranga P, Zubaid M, Sulaiman K, Rashed WA, Alsheikh-Ali AA, AlMahmeed W, Shehab A, Al Qudaimi A, Asaad N, Amin H. Impact of digoxin on mortality in patients with atrial fibrillation stratified by heartfailure: findings from gulf survey of atrial fibrillation events in the middle east. J CardiovascPharmacolTher 2015; 21: 273-279.
- Lee AY, Kutyifa V, Ruwald MH, McNitt S, Polonsky B, Zareba W, Moss AJ, Ruwald AC. Digoxin therapy and associated clinical outcomes in the MADIT-CRT trial. Heart Rhythm 2015; 12: 2010-2017.
- Markowitz M, Messineo F, Coplan NL. Aldosterone receptor antagonists in cardiovascular disease: a review of the recent literature and insight into potential future indications. ClinCardiol 2012; 35: 605-609.
- Miller SE, Alvarez RJ. Aldosterone antagonists in heart failure. J CardiovascNurs 2013; 28: E47-54.
- Verbrugge FH, Grieten L, Mullens W. New insights into combinational drug therapy to manage congestion in heart failure. Curr Heart Fail Rep 2014; 11: 1-9.
- Qavi AH, Kamal R, Schrier RW. Clinical use of diuretics in heart failure, cirrhosis, and nephrotic syndrome. Int J Nephrol 2015; 2015: 975934.
- Torp-Pederson C, Metra M, Charlesworth A, Spark P, Lukas MA, Poole-Wilson PA, Swedberg K, Cleland JG, Di Lenarda A, Remme WJ, Scherhag A. Effects of metoprolol and carvedilol on pre-existing and new onset diabetes in patients with chronic heart failure: data from the Carvedilol Or Metoprolol European Trial (COMET). Heart 2007; 93:968-973.
- Lund LH, Benson L, Dahlström U, Edner M, Friberg L. Association between use of Î²-blockers and outcomes in patients with heart failure and preserved ejection fraction. JAMA 2014; 312: 2008-2018.
- Hulkower S, Aiken BA, Stigleman S. Clinical inquiry: what is the best beta-blocker for systolic heart failure? J FamPract 2015; 64: 122-123.
- Reed BN, Sueta CA. A practical guide for the treatment of symptomatic heart failure with reduced ejection fraction (HFrEF). CurrCardiol Rev 2015; 11: 23-32.
- Chatterjee S, Biondi-Zoccai G, Abbate A, D'Ascenzo F, Castagno D, Van Tassell B, Mukherjee D, Lichstein E. Benefits of Î² blockers in patients with heart failure and reduced ejection fraction: network meta-analysis. BMJ 2013; 346: f55.
- Ng TM, Goland S, Elkayam U. Relaxin for the treatment of acute decompensated heart failure: pharmacology, mechanisms of action, and clinical evidence. Cardiol Rev 2015; 24: 194-204.
- Castrini AI, Carubelli V, Lazzarini V, Bonadei I, Lombardi C, Metra M. Serelaxin a novel treatment for acute heart failure. Expert Rev ClinPharmacol 2015; 8: 549-557.
- Wilson SS, Ayaz SI, Levy PD. Relaxin: a novel agent for the treatment of acute heart failure. Pharmacotherapy 2015; 35: 315-327.
- King JB, Bress AP, Reese AD, Munger MA. Neprilysin inhibition in heart failure with reduced ejection fraction: a clinical review. Pharmacotherapy 2015; 35: 823-833
- Macdonald PS. Combined Angiotensin Receptor/Neprilysin Inhibitors: A review of the new paradigm in the management of chronic heart failure. ClinTher 2015; 4: S0149-2918(15)01030-9.
- Buggey J, Mentz RJ, DeVore AD, Velazquez EJ. Angiotensin receptor neprilysin inhibition in heart failure: mechanistic action and clinical impact. J Card Fail 2015; 21: 741-750.
- Pham AQ, Patel Y, Gallagher B. LCZ696 (angiotensin-neprilysin inhibition): the new kid on the heart failure block? J Pharm Pract 2015; 28: 137-145.
- Filippatos G, Farmakis D, Parissis J, Lekakis J. Drug therapy for patients with systolic heart failure after the PARADIGM-HF trial: in need of a new paradigm of LCZ696 implementation in clinical practice. BMC Med 2015; 13: 35.
- Tschöpe C, Pieske B. New therapy concepts for heart failure with preserved ejection fraction. Herz 2015; 40: 194-205.
- Califf RM. LCZ696: too good to be true? Eur Heart J 2015; 36: 410-412.