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Goldman: Cecil Medicine, 23rd ed.

Copyright 2007 Saunders, An Imprint of Elsevier

Chapter 58 HEART FAILURE: MANAGEMENT AND PROGNOSIS

John J.V. McMurray

Marc A. Pfeffer

EVALUATION AND MANAGEMENT OF HEART FAILURE

Heart failure is an overarching term for a syndrome (i.e., a constellation of signs and symptoms) that encompasses a vast spectrum ofcardiovascular disorders and is associated with a greatly heightened risk of death and nonfatal adverse cardiovascular events ( Chapter 57). Treatment is initially directed toward prevention of cardiac injury (e.g., due to hypertension or myocardial infarction) or toward limitingstructural progression if cardiac damage has already occurred (e.g., left ventricular remodeling with declining left ventricular ejectionfraction) and delaying the development of symptomatic heart failure. Once symptoms develop, treatments are also directed at improvingfunctional status as well as prognosis.

Approximately one in five adults will develop heart failure. In the United States, the nearly 1 million annual hospitalizations with a primarydiagnosis of heart failure account for 5 million hospital days. The estimated cost of heart failure management ranges from $15 billion to $40billion annually, depending on the formula used.

Randomized controlled clinical trials (RCTs) supply the framework for quantifying what different therapeutic approaches can offer. Evenwhen they are definitive, RCTs only generate data about average risks and benefits of the tested therapeutic option in a selected cohort.Because an individual patient's responses can only be implied from the overall estimated group responses, RCTs cannot definitively direct

the approach of every patient or answer the myriad questions that confront the practitioner regarding the specific circumstances of thepatient. Another major limitation of RCTs is the relatively narrow time frame of observation, generally only months to several years,compared with epidemiologic experiences during decades. Despite these limitations, RCTs are the premier tool of evidence-basedmedicine, and the field of heart failure has fortunately been the focus of relatively high quality RCTs that have provided robust evidence toimprove clinical care and prognosis ( Table 58-1 ). Indeed, the implementation of evidence from RCTs into clinical practice has resulted inimpressive temporal improvements in survival after discharge from a first hospital admission for heart failure. Moreover, the age at whichsymptomatic heart failure first becomes evident has increased. Despite these tangible advances, heart failure continues to be a leadingcause of morbidity and mortality in the elderly.

TABLE 58-1 -- CONTROLLED TRIALS [*] IN SYMPTOMATIC HEART FAILURE WITH REDUCED SYSTOLIC FUNCTION

Trial,

Treatment,

and Year

Published N

Severity of

Heart

Failure

Estimated

First-Year

Placebo/Control

Group Mortality

Background

Treatment []

Treatment

Added

Trial

Duration

(years)

Primary

End Point

Relative

Risk

Reduction

(%) []

Events Prevented per

1000 Patients

Treated []

DEATH

HF

HOSP.

DEATH

OR HF

HOSP.

ACE INHIBITORS

CONSENSUS,1987 [a]

253 End stage 52 Spironolactone Enalapril, 20mg bid

0.54 [] Death 40 146

SOLVD-T,1991 [b]

2569 Mild-severe 15.7 Enalapril, 20mg bid

3.5 Death 16 45 96 108

-BLOCKERS

CIBIS-2,1999 [c]

2647 Moderate-severe

13.2 ACE-I Bisoprolol,10 mg qd

1.3 [] Death 34 55 56

MERIT-HF,1999 [d]

3991 Mild-severe 11.0 ACE-I MetoprololCR/XL, 200

mg qd

1.0 [] Death 34 36 46 63

COPERNICUS,2001 [e]

2289 Severe 19.7 ACE-I Carvedilol,25 mg bid

0.87 [] Death 35 55 65 81

ANGIOTENSIN RECEPTOR BLOCKERS

Val-HeFT,2001 [8]

5010 Mild-severe ~8.0 ACE-I Valsartan,160 mg bid

1.9 CV deathormorbidity

13 0 35 33 []

CHARM-Alternative,2003 [7]

2028 Mild-severe 12.6 BB Candesartan,32 mg qd

2.8 CV deathor HFhosp.

23 30 31 60

ter 58 - HEART FAILURE: MANAGEMENT AND PROGNOSIS fr... http://remoto.dgb.uanl.mx:2065/das/book/body/108023714-4/0/14

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CHARM-Added,2003 [9]


10.6 ACE-I + BB Candesartan,32 mg qd

3.4 CV deathor HFhosp.

15 28 47 39

ALDOSTERONE BLOCKADERALES,1999 [11]

1663 Severe ~25 ACE-I Spirolactone,2550 mg qd

2.0 [] Death 30 113 95

HYDRALAZINE-ISDN

V-HeFT-1,1986 [f]

459 Mild-severe 26.4 Hydralazine,75 mg tid-qid

2.3 Death 34 52 0

ISDN, 40 mgqid

A-HeFT,2004 [14]


~9.0 ACE-I + BB +spironolactone

Hydralazine,75 mg tid

0.83 [] Composite 40 80

ISDN, 40 mgtid

DIGITALIS GLYCOSIDESDIG, 1997 [13] 6800 Mild-severe ~11.0 ACE-I Digoxin 3.1 Death 0 0 79 73

CRT

COMPANION,2004 [17]

925 Moderate-severe

19.0 ACE-I + BB +spironolactone

CRT 1.35 [] Death oranyhospitaladmission

19 38 87

CARE-HF,2005 [g]

813 Moderate-severe

12.6 ACE-I + BB +spironolactone

CRT 2.45 Death or CVhospitaladmission

37 97 151 184

CRT-D

COMPANION,2004 [17] 903 Moderate-severe 19.0 ACE-I + BB +spironolactone CRT-ICD 1.35 [] Death oranyhospitaladmission

20 74 114

IMPLANTABLE CARDIOVERTER DEFIBRILLATOR

SCD-HeFT,2005 [16]

1676 Mild-severe ~7.0 ACE-I + BB ICD 3.8 Death 23

VENTRICULAR ASSIST DEVICE

REMATCH,2001 [h]

129 End stage 75 ACE-I +spironolactone

LVAD 1.8 Death 48 282

Trial,

Treatment,

and Year

Published N

Severity of

Heart

Failure

Estimated

First-Year

Placebo/Control

Group Mortality

Background

Treatment []

Treatment

Added

Trial

Duration

(years)

Primary

End Point

Relative

Risk

Reduction

(%) []

Events Prevented per

1000 Patients

Treated []

DEATH

HF

HOSP.

DEATH

OR HF

HOSP.

Modified from McMurray JJ, Pfeffer MA: Heart failure. Lancet 2005;365:18771889.

ACE-I = ACE inhibitor; BB = -blocker; CRT = cardiac resynchronization therapy (biventricular pacing); CRT-D = CRT device that also

defibrillates; CV = cardiovascular; HF hosp. = patients with at least one hospital admission for worsening heart failuresome patients hadmultiple admissions; ICD = implantable cardioverter defibrillator; ISDN = isosorbide dinitrate; LVAD = left ventricular assist device.

* Excluding active-controlled trials.

In more than one third of patients, ACE-I + BB means that ACE inhibitors were used in almost all patients and BB in the majority; most patients were also takingdiuretics, and many digoxin (except in DIG). Spirono-lactone was used at baseline in 5% Val-HeFT, 8% MERIT-HF, 17% CHARM-Added, 19% SCD-HeFT, 20%COPERNICUS, and 24% CHARM-Alternative.

Relative risk reduction in primary end point. Stopped early for benefit.

Individual trials may not have been designed or powered to evaluate effect of treatment on these outcomes.

Primary end point that also included treatment of heart failure with intravenous drugs for 4 hours or more without admission and resuscitated cardiac arrest (both addedsmall numbers).


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a The CONSENSUS Trial Study Group: Effects of enalapril on mortality in severe congestive heart failure. Results of the Cooperative North Scandinavian EnalaprilSurvival Study (CONSENSUS). N Engl J Med 1987;316:14291435.

b The SOLVD Investigators: Effect of enalapril on survival in patients with reduced left ventricular ejection fractions and congestive heart failure. N Engl J Med1991;325:293302.

c The Cardiac Insufficiency Bisoprolol Study II (CIBIS-II): A randomised trial. Lancet 1999;353:913.

d Effect of metoprolol CR/XL in chronic heart failure: Metoprolol CR/XL Randomised Intervention Trial in Congestive Heart Failure (MERIT-HF). Lancet1999;353:20012007.

e Packer M, Coats AJ, Fowler MB, et al: Effect of carvedilol on survival in severe chronic heart failure. N Engl J Med 2001;344:16511658.

f Cohn JN, Archibald DG, Ziesche S, et al: Effect of vasodilator therapy on mortality in chronic congestive heart failure. Results of a Veterans Administration CooperativeStudy. N Engl J Med 1986;314:15471552.

g Cleland JG, Daubert JC, Erdmann E, et al: The effect of cardiac resynchronization on morbidity and mortality in heart failure. N Engl J Med 2005;352:15391549.

h Rose EA, Gelijns AC, Moskowitz AJ, et al: Long-term mechanical left ventricular assistance for end-stage heart failure. N Engl J Med 2001;345:14351443.

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