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1460 Los fármacos para la insuficiencia cardiaca crónica ............................................. ................................. p 9
volumen 56
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La insuficiencia cardíaca se asocia generalmente con disfunción ventricular ▶ Unless there is a specifi c contraindication, all patients with heart failure with
reduced ejection fraction (LVEF ≤ 40%) should take both an ACE inhibitor
izquierda. De acuerdo con las directrices recientes, los pacientes con una fracción
and a beta blocker, and if volume overloaded, a diuretic as well.
de eyección ventricular izquierda (FEVI) ≤ 40% se considera que tienen
insuficiencia cardíaca con fracción de eyección reducida (ICFER) o insuficiencia ▶ An angiotensin receptor blocker (ARB) is recommended for patients who
cannot tolerate an ACE inhibitor.
cardíaca sistólica. Los pacientes con una FEVI ≥ 50% y síntomas de insuficiencia
▶ Addition of an aldosterone antagonist can reduce mortality and
cardíaca se considera que tienen insuficiencia cardíaca con fracción de eyección
hospitalization in patients with symptomatic heart failure or with left
conservada (ICFEP) o insuficiencia cardíaca diastólica; hay poca evidencia de que ventricular dysfunction after a myocardial infarction.
el tratamiento farmacológico mejora los resultados clínicos en estos pacientes. 1,2 El
tratamiento de la insuficiencia cardíaca aguda no se incluye aquí. ▶ Addition of a combination of hydralazine and isosorbide dinitrate to standard
therapy has been shown to reduce mortality and symptoms in black patients
with NYHA class III-IV heart failure with reduced ejection fraction.
▶ Digoxin can decrease symptoms and lower the rate of hospitalization for
Inhibidores de la ECA - Todos los pacientes con insuficiencia cardíaca con
heart failure, but it does not reduce mortality.
fracción de eyección reducida deben recibir un inhibidor de la enzima convertidora
de angiotensina (ACE). Estos fármacos mejoran los síntomas (generalmente más ▶ There is little evidence that drug treatment improves clinical outcomes in
de 4-12 semanas), disminuir la incidencia de hospitalización, y prolongar la patients with heart failure with preserved ejection fraction (HFpEF).
cardíaca.
99
Publicado por The Medical Letter, Inc. • Una Organización t fi sin ánimo de lucro
The Medical Letter ®
Vol. 57 (1460) January 19, 2015
Dosage – ARBs should be started at low doses and titrated to the highest Choice of a Beta Blocker – Carvedilol, extended-release metoprolol
tolerated dose, which is usually achieved by doubling the dose until the succinate, and bisoprolol have been shown to reduce mortality and
maximum daily dose (listed in Table 1) is reached. hospitalization in patients with heart failure with reduced ejection fraction.
Bisoprolol is not approved by the FDA for treatment of heart failure.
There is no defi nitive clinical trial comparing extended-release
Cautions – As with ACE inhibitors, blood pressure, renal function, and
metoprolol succinate with carvedilol. Carvedilol has been shown to
serum potassium concentrations should be monitored in patients taking
reduce the incidence of diabetes mellitus, 7 hospitalization for heart failure,
an ARB. Angioedema could occur in patients taking an ARB who had
and inappropriate defi brillator therapy. 8 The advantages of
previously developed it while taking an ACE inhibitor. Like ACE inhibitors,
extended-release metoprolol succinate are once-daily dosing, less
ARBs can increase fetal mortality and should not be used during
hypotension, and more selective beta-1 blockade that may reduce the
pregnancy.
risk of bronchospasm.
Choice of an ARB – Candesartan and valsartan are the only ARBs aldosterone antagonists have been shown to reduce the risk of
approved by the FDA for treatment of heart failure; losartan, which is hospitalization and death. 9-11 When used in addition to standard therapy in
available generically, has also been widely used. 3,4 patients with heart failure after myocardial infarction, one study found that
eplerenone signifi cantly reduced the primary endpoints of all- cause
mortality and mortality or hospitalization for cardiovascular reasons. 12 Guidelines
BETA BLOCKERS — Unless there is a specifi c contraindication, all recommend adding an aldosterone antagonist after an acute myocardial
patients with stable heart failure with reduced ejection fraction should infarction in patients with heart failure symptoms and an LVEF ≤ 40%. In
receive a beta blocker in addition to an ACE inhibitor. Use of bisoprolol, a study in patients with heart failure with preserved ejection fraction,
carvedilol, or extended-release metoprolol succinate in addition to an spironolactone improved non- invasive measures of diastolic function, but
ACE inhibitor consistently leads to a 30-40% reduction in hospitalization it did not improve exercise capacity or quality of life. 13 In another trial, use
and mortality in adults with New York Heart Association (NYHA) class
of spironolactone did not signifi cantly reduce the incidence of the
II–IV heart failure. The effi cacy of adding a beta blocker to standard
primary composite endpoint of cardiovascular death, cardiac arrest, or
therapy for heart failure is less certain in children and adolescents and in
heart failure hospitalization compared to placebo. 14
patients with a reduced ejection fraction who are asymptomatic. 5
Dosage – Beta blockers should be started at low doses and increased or an estimated GFR <30 mL/min/1.73 m 2). Renal function and serum
gradually, usually at 2-week intervals, to the highest tolerated dose. Full creatinine concentrations should be monitored during treatment.
10
The Medical Letter ®
Vol. 57 (1460) January 19, 2015
Table 1. Some Drugs for Chronic Heart Failure with Reduced Ejection Fraction 1
7. Both of these drugs are available generically as single agents. Isosorbide dinitrate is available in 5, 10, 20, and 30-mg tablets and hydralazine in 10, 25, 50,
and 100-mg tablets.
8. FDA-approved as adjunctive therapy for treatment of heart failure in black patients.
11
The Medical Letter ®
Vol. 57 (1460) January 19, 2015
Choice of an Aldosterone Antagonist – Eplerenone may be similar in Adverse Effects – The most common adverse effect of diuretic therapy is
effectiveness to spironolactone and may have less anti-androgenic hypokalemia. Diuretics can also cause worsening of renal function.
activity, but it costs much more. Comparative studies of their use in heart
failure are lacking.
Choice of a Diuretic – Torsemide is better absorbed than furosemide
and has a longer duration of action, but there is no clinical evidence that
VASODILATORS — Use of hydralazine plus isosorbide dinitrate may be torsemide or bumetanide is more effective than furosemide, which has
benefi cial for some patients. The addition of a fi xed-dose combination of been in use much longer.
12
The Medical Letter ®
Vol. 57 (1460) January 19, 2015
1. CW Yancy et al. 2013 ACCF/AHA guideline for the management of heart failure: a Aldactone Evaluation Study Investigators. N Engl J Med 1999; 341:709.
report of the American College of Cardiology Foundation/American Heart Association
Task Force on practice guidelines. Circulation 2013; 128:e240. 12. B Pitt et al. Eplerenone, a selective aldosterone blocker, in patients with left ventricular
dysfunction after myocardial infarction. N Engl J Med 2003; 348:1309.
2. J Lindenfeld et al. HFSA 2010 comprehensive heart failure practice guideline. J Card
Fail 2010; 16:e1. 13. F Edelmann et al. Effect of spironolactone on diastolic function and exercise capacity
3. H Svanström et al. Association of treatment with losartan vs candesartan and mortality in patients with heart failure with preserved ejection fraction: the Aldo-DHF
among patients with heart failure. JAMA 2012; 307:1506. randomized controlled trial. JAMA 2013; 309: 781.
4. MA Konstam et al. Effects of high-dose versus low-dose losartan on clinical outcomes in 14. B Pitt et al. Spironolactone for heart failure with preserved ejection fraction. N Engl J
patients with heart failure (HEAAL study): a randomised, double-blind trial. Lancet Med 2014; 370:1383.
2009; 374:1840. 15. KB Shah et al. The adequacy of laboratory monitoring in patients treated with
spironolactone for congestive heart failure. J Am Coll Cardiol 2005; 46:845.
5. RE Shaddy et al. Carvedilol for children and adolescents with heart failure: a
randomized controlled trial. JAMA 2007; 298:1171. 16. AL Taylor et al. Early and sustained benefi t on event-free survival and heart failure
hospitalization from fi xed-dose combination of isosorbide dinitrate/hydralazine:
6. LH Lund et al. Association between use of β-blockers and outcomes in patients with consistency across subgroups in the African-American Heart Failure Trial. Circulation
heart failure and preserved ejection fraction. JAMA 2014; 312:2008. 2007; 115:1747.
7. C Torp-Pederson et al. Effects of metoprolol and carvedilol on pre-existing and new 17. GISSI-HF investigadores et al. Efecto de n-3 ácidos grasos poliinsaturados en los pacientes
onset diabetes in patients with chronic heart failure: data from the Carvedilol Or con insuficiencia cardíaca crónica (el ensayo GISSI-HF): un estudio doble ciego,
Metoprolol European Trial (COMET). Heart 2007; 93:968. aleatorizado, controlado con placebo. The Lancet 2008; 372: 1223.
8. MH Ruwald. Impacto de carvedilol y metoprolol en 18. M Gheorghiade et al. Efecto de aliskiren en la mortalidad tras el alta y reingresos por
inapropiada implantable terapia desfibrilador cardioversor-fi de: el ensayo insuficiencia cardiaca en pacientes hospitalizados por insuficiencia cardíaca: el
MADIT-CRT (Desfibrilador automático De multicéntrico ensayo aleatorizado ASTRONAUTA. JAMA 2013; 309: 1125.
La implantación con terapia de resincronización cardiaca). J Am Coll Cardiol 2013; 62:
1343. 19. JJ McMurray et al. La angiotensina-neprilisina frente enalapril en la insuficiencia cardíaca. N
9. G Sayer y G Bhat. El sistema renina-angiotensina-aldosterona y la insuficiencia Engl J Med 2014; 371: 993.
cardíaca. Clin Cardiol 2014; 32:21. 20. O Vardeny et al. neprilisina Combinado y la inhibición del sistema renina-angiotensina para el
10. F Zannad et al. Eplerenona en pacientes con insuficiencia cardíaca sistólica y síntomas tratamiento de la insuficiencia cardíaca. JACC del corazón no 2014; 2: 663.
leves. N Engl J Med 2011; 364: 11.
11. B Pitt et al. El efecto de la espironolactona sobre la morbilidad y la mortalidad en
pacientes con insuficiencia cardíaca grave. aleatorizado
EDITOR EN JEFE: Marcos Abramowicz, MD; EDITOR EJECUTIVO: Gianna Zuccotti, MD, MPH, FACP, Escuela Médica de Harvard; EDITOR: Jean-Marie Pflomm, Pharm.D .;
Asistentes de editores, información sobre drogas: Susan M. Daron, Pharm.D., Corinne Z. Morrison, Doctor en Farmacia., Michael P. Viscusi, Pharm.D .; CONSULTAR LOS REDACTORES: Brinda M. Shah, Pharm.D.,
F. Peter Swanson, MD; MAYOR editor asociado: Amy Faucard
Editores colaboradores: Carl W. Bazil, MD, Ph.D., Universidad de Columbia Colegio de Médicos y Cirujanos; Vanessa K. Dalton, MD, MPH, Universidad de Michigan Medical School; Eric J. Epstein, MARYLAND, Albert Einstein College of
Medicine; Jane P. Gagliardi, MD, MHS, FACP, Escuela de Medicina de la Universidad de Duke de; Jules Hirsch, MD, Universidad Rockefeller; David N. Juurlink, BPhm, MD, Ph.D., Centro de Ciencias de la Salud Sunnybrook; Richard B.
Kim, MD, Universidad de Ontario Occidental; Hans Meinertz, MD, Hospital de la Universidad de Copenhague; Sandip K. Mukherjee, MD, FACC, Escuela de Medicina de Yale; Dan M. Roden, MD, Escuela de la Universidad de Vanderbilt de
Medicina; Esperance AK Schaefer, MD, MPH,
Escuela Médica de Harvard; F. Estelle R. Simons, MD, Universidad de Manitoba; Neal H. Steigbigel, MD, Escuela Universitaria de Medicina de Nueva York; Arthur MF Yee, MD, Ph.D., FACR,
Weill Medical College de la Universidad de Cornell
JEFE DE REDACCIÓN: Susie Wong; Subdirector asistente: Liz Donohue; ASISTENTE EDITORIAL: Cheryl Brown
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VICEPRESIDENTE Y EDITOR: Yosef Wissner-Levy
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