Download heart failure

New Strategies in the Management
of Heart Failure
Dr. Hassan Chamsi Pasha
MD, FRCP(Lond), FRCP(Ire),
FRCP(Glasg), FACC
Head, Non–Invasive Cardiology
King Fahd Armed Forces Hospital
Heart failure

Approximately 4.6 million Americans currently
have heart failure.
 400,000 new cases occur each year.
 Prevalence of the disease increases with
age, affecting approximately 1% of persons in
their fifth decade and nearly 10% of those
aged 80 to 89.
South Med J 2001 ,94(2):166-174
Heart failure






Contributes directly or indirectly to approximately 260,000
deaths annually.
Primary diagnosis in 870,000 hospital discharges.
Five-year survival after the diagnosis is only 25% in
men and 38% in women.
In more severe disease, 1-year mortality approaches
30-50%.
For all patients, median survival is 1.7 years in men
and 3.2 years in women.
Annual cost exceeding $34 billion.
Pharmacotherapy 20(7):787-804, 2000.

One third of patients who are hospitalized for
heart failure either die or require readmission
within 60 days of hospital discharge.
 One half are readmitted within 90 days.
Mechanisms of Heart Failure

Disease progression is related to structural
changes in the heart and blood vessels that
lead to ventricular remodeling.
 Remodeling process is characterized by
alterations in the size and shape of the left
ventricle and is triggered by activation of
endogenous neurohormonal systems, primarily
the renin-angiotensin system (RAS) and the
sympathetic nervous system (SNS).
Goals of Treatment

The primary goal of treatment has shifted
from symptomatic relief to slowing or
arresting disease progression.
 Neurohormonal abnormalities, not
hemodynamic abnormalities, are responsible
for disease progression
Usual Treatment Today
AIMS OF HEART FAILURE MANAGEMENT
TO IMPROVE SYMPTOMS
 DIURETICS
 DIGOXIN
 ACE INHIBITORS
TO IMPROVE SURVIVAL
 ACE INHIBITORS
  BLOCKERS
 ORAL NITRATES PLUS HYDRALAZINE
 SPIRONOLACTONE
Davies et al. BMJ 2000;320:428-431
HF: Mortality Remains High



ACEI
RISK REDUCTION 35%
(MORTALITY AND HOSPITALIZATIONS)1
 BLOCKERS
RISK REDUCTION 38%
(MORTALITY AND HOSPITALIZATIONS)2
ORAL NITRATES AND HYDRALAZINE
BENEFIT VS. PLACEBO; INFERIOR TO ENALAPRIL
(MORTALITY)
HOWEVER: 4-YEAR MORTALITY REMAINS
~40%
Davies et al. BMJ 2000;320:428-431 (metanalysis: 32 trials, n=7105) 2
Gibbs et al. BMJ 2000;320:495-498 (metanalysis: 18 trials, n=3023)
Nonpharmacologic interventions






smoking cessation.
Weight reduction
Avoidance of alcohol.
Limiting sodium intake (no more than 3 g
daily).
Daily weight.
Contact physician if body weight increases by
2 lb or more.

Benefits of ACE inhibitor therapy may not
become apparent for 1 or 2 months after
initiation of treatment.
 Approximately 90% of patients with heart
failure tolerate long-term ACE inhibitor
therapy.
Aspirin-ACE Inhibitor Interaction

Studies are largely contradictory, but do
reiterate the possibility of an interaction.
 Low dosages (</= 100 mg/day) of aspirin
appear to be safer than higher dosages.
Pharmacotherapy 20(6):698-710, 2000
B blockers






Four randomized, double-blind, placebocontrolled clinical trials:
mortality reduced 65% by carvedilol,
34% by metoprolol,
33% by bisoprolol;
trials were ended early.
Bucindolol: no significant effect on mortality.
[Am J Health-Syst Pharm 58(02):140-145, 2001.
MERIT-HF study

3991 patients with heart failure from 313
centers in 14 countries randomly assigned to
metoprolol CR/XL or placebo, in addition to
their standard heart failure regimens.
MERIT-HF trial
Metoprolol CR/XL reduced the risk:
By 19%, for all-cause mortality or all-cause hospitalizations
By 31%, for total mortality or hospitalizations due to
worsening heart failure
By 32%, for death or heart transplant by
By 39%, for cardiac death or nonfatal MI
By 32%, for mortality and hospitalization or emergency
department visit due to worsening heart failure
Hjalmarson et al.
JAMA 2000; 283: 1295-1302
Carvedilol

Four US studies:
1,094 patients with mild, moderate, or severe
heart failure receiving standard therapy with a
diuretic, an ACE inhibitor, and digoxin.
 Overall mortality in carvedilol group was
3.2% vs 7.8%, a reduction of 65%.
 27% reduction in hospitalization
 38% reduction in the combined risk of
hospitalization or death.
COPERNICUS trial

Enrolled 2289 patients with severe HF (LVEF
<25%), randomized to carvedilol in a target
dose of 25 mg bid for up to 29 months.
 Trial was stopped early for efficacy.
COPERNICUS
and CAPRICORN
COPERNICUS: Effect of carvedilol on the combined
risk of morbidity and mortality
Endpoint
Relative risk
reduction
Odds ratio
p value
Death or
hospitalization
for any reason
24%
0.76
0.00004
Death or
hospitalization
for a CV reason
27%
0.73
0.00002
Death or
hospitalization for
HF
31%
0.69
0.000004
COPERNICUS
and CAPRICORN
COPERNICUS: Hospitalizations
Endpoint
Reduction with
carvedilol
p value
Total days in
hospital
24%
0.0005
Number of
hospitalizations
27%
0.0017
Days per
hospitalization
31%
0.015
CAPRICORN trial

Examined the effect of carvedilol in patients
with left ventricular dysfunction (LVEF < 40%)
after an MI, with or without HF.
COPERNICUS
and CAPRICORN
CAPRICORN: Primary endpoints
Endpoint
Relative risk
reduction
Odds ratio
p value
All-cause
mortality
151 (15%)
0.77 (0.60-0.98)
0.031
All-cause
mortality or CV
hospitalization
367 (37%)
0.92 (0.80–1.07)
0.296
COPERNICUS
and CAPRICORN
CAPRICORN
Endpoint
Hazard ratio
p value
Sudden death
0.74
0.098
HF
hospitalization
0.86
0.215
Nonfatal MI
0.59
0.014
0.71
0.002
All-cause
mortality and
nonfatal MI
Packer :
“Instead of prescribing carvedilol to such
patients in the midst of their acute illness, it
would be prudent first to take measures to
stabilize their clinical condition"
N Engl J Med 2001; 344(22):1651-8.
3
Packer
 The use of carvedilol for severe HF would
prevent approximately 70 deaths per 1000
patients treated for 1 year
 This compares with 20-40 deaths prevented
with ACE inhibitors or beta blockers in mild to
moderate HF, and with about 50 deaths
prevented with an aldosterone antagonist in
severe HF.
N Engl J Med 2001; 344(22):1651-8.
CIBIS-II

Cardiac Insufficiency Bisoprolol Study II
(CIBIS-II) compared a ß-blocker-containing
regimen with standard therapy alone (diuretic
plus ACE inhibitor) in 2,647 patients with
NYHA class III or IV heart failure
 Bisoprolol:
34% reduction in mortality
32% reduction in hospitalization.
Lancet 1999; 353:9-13
BEST trial

The Beta-blocker Evaluation of Survival Trial.
 Randomized 2708 patients with NYHA Class
III (92%) or IV (8%) HF and an ejection
fraction of 35% or lower to bucindolol or
placebo.
 Mortality was not significantly different
between the two groups .
May 31, 2001 issue of the New England Journal of
Medicine.
Bucinodol and
carvedilol in HF
BEST results
Endpoint
Placebo
Bucindolol
Hazard ratio
p value
Death
33%
30%
0.90
0.10
CV death
29%
25%
0.86
0.04
Hospitalized
due to CHF
42%
35%
0.78
<0.001
3%
2%
0.69
0.12
35%
32%
0.87
0.04
Heart transplant
Death or heart
transplant
BEST investigators. N Engl J Med 2001; 344(22):1659-67.
COMET TRIAL
The ongoing Carvedilol and Metoprolol
European Trial, which involves 3,000 patients
with NYHA class II to class IV heart failure, is
testing the hypothesis that multiple-receptor
blockade with carvedilol offers a therapeutic
advantage over selective adrenergic
blockage with metoprolol.
ß-blocker therapy

Although ejection fraction continues to
improve at the highest dosage of Carvedilol
(25 mg twice daily or 50 mg twice daily in
heavier patients), significant treatment effect
(two thirds or more of maximum mortality
benefit) is seen at 6.25 mg twice daily.
 Continue at a minimum dosage of 6.25 mg
twice daily and do not abandon therapy if
higher doses are not tolerated.
beta-Blocker withdrawal:
The song of Orpheus
Morimoto :
 13 patients with dilated cardiomyopathy who were
receiving long-term beta-blockade;
 Investigators withdrew the therapy to see if the
patients would continue to do well.
 Seven of the 13 patients deteriorated, including 4
who died either suddenly or of progressive pump
dysfunction.
Am Heart J 1999;138:387-9.
ATLAS study
Increasing ACE inhibitor doses from low to
high confers relatively modest absolute
reductions in mortality (8%).
Eur Heart J 1998; 19(suppl):142
Adding ß-blockade to intermediate doses of
ACEI reduces mortality by 30% or more.
Lancet 1999; 353:9-13
Lancet 1999; 353:2001-2007
To optimally slow disease progression, it may,
therefore, be preferable to add ß-blockade to
moderate doses of ACE inhibitors, then
increase the ACE inhibitor dose later, titrating
upward as each successive dose is tolerated.
ß-blocker therapy


Taking the ACE inhibitor 2 hours after the
carvedilol or taking carvedilol with food may
reduce this hypotensive effect.
A temporary reduction in the dose of the
ACE inhibitor may also be required.
Am J Cardiol 1999; 83(suppl 2A):1A-38A
-Blockers underutilized in heart
failure: major side effects
Side effect
Study population US carvedilol study
Weight gain
64%
10%
Fatigue
61%
25%
Dizziness
35%
33%
Dyspnea
27%
22%
Hypertension
22%
9%
Hyperglycemia
22%
13%
Bradycardia
17%
9%
Diarrhea
9%
12%
Depression
8%
N/A
Impotence
5%
N/A
ELITE Study

Evaluation of Losartan in the Elderly (ELITE)
study:
 722 patients to compare effects of losartan
and captopril on renal function.
 losartan associated with a 46% lower risk of
mortality than captopril.
Lancet 1996; 2:47-54
ELITE Study
The study was not powered to investigate
mortality, and after adjustment for the
multiplicity of end points, no difference was
seen in frequency of hospitalization or
combined morbidity and mortality risk
Pharmacotherapy 20(7):787-804, 2000
RESOLVD study

Randomized Evaluation of Strategies for Left
Ventricular Dysfunction (RESOLVD) study
involved 768 patients.
 No significant differences in the rate of cardiac
events among patients treated with
candesartan, enalapril, or the combination.
Eur Heart J 1998; 19(suppl):
VALSARTAN Heart Failure Trial

LONG-TERM CARDIAC MORBIDITY & MORTALITY TRIAL

CHRONIC STABLE HEART FAILURE PATIENTS

VALSARTAN ADDED TO USUAL HEART FAILURE
THERAPY (ACEIS; DIURETICS; DIGOXIN;  BLOCKERS)
•
•
5,010 PATIENTS
300 CENTERS IN 16 COUNTRIES
Val-HeFT DESIGN
HF PATIENTS
>18 YR; EF <40%; NYHA
II-IV
Cohn et al. J Card
Fail 1999;5:155-160
RECEIVING USUAL THERAPY
INCLUDING ACEI, DIURETICS,
DIGOXIN,  BLOCKERS
(STRATIFIED RANDOMIZATION)
RANDOMIZED TO
VALSARTAN
40 MG BID
TITRATED TO
160 MG BID
Placebo
906 DEATHS (EVENTS
RECORDED)
All Cause Mortality
SURVIVAL PROBABILITY
1.0
P = 0.8
0.9
0.8
VALSARTAN
0.7
0
3
PLACEBO
6
9
12
15
18
21
TIME SINCE RANDOMIZATION (MONTHS)
24
27
COMBINED ALL CAUSE MORTALITY
AND MORBIDITY
EVENT-FREE PROBABILITY
1.0
13.3%
RISK REDUCTION
P= 0.009
0.9
0.8
0.7
VALSARTAN
0.6
0
3
6
PLACEBO
9
12
15
18
TIME SINCE RANDOMIZATION
RANDOMIZATION (MONTHS)
21
24
27
HF HOSPITALIZATION
EVENT-FREE PROBABILITY
1.0
27.5%
RISK
REDUCTION
P =0.00001
0.9
0.8
VALSARTAN
0.7
0
3
6
PLACEBO
9
12
15
18
21
TIME SINCE
SINCE RANDOMIZATION
RANDOMIZATION (MONTHS)
(MONTHS)
TIME
24
27
*
SECONDARY VARIABLES
CHANGE FROM BASELINE
EF (%)†
QUALITY OF LIFE
(MLWHF* SCORE)†
WORS
E
p = 0.005
3
2
1
0
BETTE
R
N=1557 N=1544
MINNESOTA LIVING WITH HEART FAILURE
† ENDPOINT ANALYSIS
p= 0.001
5
4
3
2
1
0
N=2509
PLACEBO
N=2499
VALSARTAN
COMBINED MORBIDITY/MORTALITY
IN SUBGROUPS
% Patients FAVORS VALSARTAN
All Patients 100
< 65
 65
Male
Female
EF < 27
EF 27
ACEI (Yes)
ACEI (No)
BB (Yes)
BB (No)
IHD (Yes)
IHD (No)
FAVORS PLACEBO
47
53
80
20
50
50
93
7
35
65
57
43
0.3
0.4
0.5
0.6
0.7
0.8
0.9
1
1.1
1.2
1.3
1.

ARBs offer an alternative to ACE inhibitors in
the management of hypertension, especially for
ACE-inhibitor-intolerant patients. ACE inhibitors
remain the drugs of choice for patients with
heart failure, left ventricular dysfunction after
MI, and diabetic nephropathy; ARBs offer these
patients an alternative when ACE inhibitor
therapy is not tolerated.
Am J Health-Syst Pharm 2001: 58(8):671-683
Combination therapy

The addition of an ARB offers more complete
angiotensin II receptor blockade of the RAS
than can be obtained by ACE inhibitors alone.
 Combination therapy preserves the benefits
of bradykinin potentiation offered by ACE
inhibitors while providing potential antitrophic
influences of AT2 receptor stimulation
 May play an increased role in the treatment of
chronic HF in the future.
Am Heart J 2000 : 140(3):361-366
Aldosterone Antagonists


Randomized Aldactone Evaluation Study
involved 1,663 patients with severe heart
failure (NYHA class III or IV) of ischemic or
nonischemic origin.
Most patients received dosages of 25 mg
daily in addition to the conventional
background therapy
N Engl J Med 1999; 341:709-717
Aldosterone Inhibition and Heart
Failure: Too Good to Be True?

The Randomized Aldactone Evaluation Study
(RALES) h stunningly positive results.
 Spironolactone, available for more than 40
years
 Reduce the mortality rate by 30% in patients
with advanced heart failure.
 Hospitalization rate for worsening heart failure
was reduced by 35%.
American Heart Journal 2001,1:141
DIG trial

Digitalis Investigation Group (DIG), the
National Institutes of Health .
 To study to digoxin's effect on survival and
morbidity in 7788 patients who remained
symptomatic while taking diuretics and ACE
inhibitors
 No significant difference when deaths from all
cardiovascular causes (29.9% digoxin vs
29.5% placebo, RR=1.10, p=0.78)
DIG trial

Digoxin significantly reduced the rate of
hospitalizations (26.8%) compared with
placebo (34.7%, RR=0.72, p<0.001).
 Admissions were fewer when all
cardiovascular reasons were combined,
including myocardial infarction and
supraventricular arrhythmias (49.9% vs 54.4,
RR=0.87, p<0.001).




Intermittent inotropic infusion therapy reported
excess mortality with dobutamine. Dobutamine
infusions were titrated to produce an optimal
hemodynamic profile; mean dosages were 8.1
µg/kg/minute (maximum 15 µg/kg/min).
Death occurred in 32% (10/31) of dobutaminetreated patients compared with 14% (4/29) of
placebo-treated patients over 24 weeks.
Causes of death assumed to result from arrhythmias
(sudden cardiac death).
Lower dosages of inotropes may be associated with
improvements in quality of life with lower risk of
mortality.

Long-term therapy with phosphodiesterase
inhibitors (e.g., milrinone, venarinone) :excess
mortality
 Intermittent intravenous inotropic agent may be of
value in improving the quality of life or as a bridge
to cardiac transplantation.
 Catecholamine infusions have been associated with
excess mortality.
 Cardiac transplantation, left ventricular assist
devices, and total artificial hearts are limited by
technical, logistic, and cost issues
Pharmacotherapy 20(7):787-804, 2000.

Hydralazine-isosorbide dinitrate should be
considered in patients with contraindications
to ACE inhibitors. The major limitation with
the combination is the frequency of adverse
effects at dosages recommended for heart
failure.
Calcium Channel Antagonists

May worsen heart failure
 Trials of verapamil, diltiazem, and nifedipine
showed detrimental effects in heart failure.
 Vasoselective dihydropyridines, such as
amlodipine and felodipine :no negative
effects.
PRAISE trial

Amlodipine 10 mg/day or placebo to 1153
patients with class III-IV disease. All patients
also received digoxin, a diuretic, and an ACE
Inhibitor.
 No difference was observed in all-cause
mortality or combined end points of death and
adverse clinical events in the two groups
(p=0.07).
 Amlodipine and felodipine have few or no
beneficial effects..
DDD pacing

Intraventricular conduction delay may hamper
the ability of the heart to contract in an
organized manner, with contraction of
different segments occurring at less than
optimal times
 DDD pacing of the right sided chambers may
be beneficial in selected dilated
cardiomyopathy patients
MUSTIC
Change in outcome measures with active pacing in
MUSTIC
Outcome
measure
% change
p value
Mean (+SD)
distance walked
+23%
<0.001
Quality of life
score
+32%
<0.001
Peak oxygen
uptake
+8%
<0.03
-66%
<0.05
Hospitalizations
Diastolic Heart Failure

Half of heart failure subjects in the community
have normal LV systolic function.
 Major contributor to hospital admissions, but
is often overlooked in studies that focus only
on patients with impaired systolic function
 Hypertension, coronary artery disease, the
normal aging process, obesity, and diabetes
mellitus are associated with diastolic
dysfunction
Cardiology Clinics 2000 :18 ,3
Diastolic heart failure

Currently, there are no therapies that
specifically affect the rate of calcium
sequestration or protein phosphorylation,
which would produce specific therapy for
diastolic failure.
 Therapy currently is based on the underlying
cardiovascular disorder and the use of
pharmacologic agents that appear to
specifically influence known pathophysiologic
abnormalities
 Optimal treatment of diastolic heart failure
has not yet been defined.
Goals of Therapy for Diastolic Heart
Failure
Treat underlying cardiovascular disease:
 Coronary artery disease
 Hypertension
 Diabetes
 Atrial fibrillation
Avoid volume depletion ( may predispose to:
Orthostatic symptoms
Tachycardia
Stimulation of vasodepressor syncope
 Facilitate
diastolic filling time
Slow heart rate.
beta Blockade
Avoid chronotropic/inotropic stimulation.
with agents, such as:
Digoxin
Theophylline
Ephedrine and decongestants
Caffeine
 Reverse
or minimize ventricular hypertrophy:
Afterload reduction
Angiotensin II blockade
Cardiology Clinics
Volume 18 • Number 3 • August 2000
‫موقع الدكتور حسان شمسي باشا على اإلنترنت‬
‫‪www.khayma.com/chamsipasha‬‬
Heart Failure Society Guidelines: A
Model of Consensus and Excellence

Committee Members: Kirkwood F. Adams, Jr., MD,
Chair, Kenneth L. Baughman, MD Marvin A. Konstam,
MD, William G. Dec, MD Peter Liu, MD, Uri Elkayam,
MD Barry M. Massie, MD, Alan D. Forker, MD J.
Herbert Patterson, PharmD, Mihai Gheorghiade, MD
Marc A. Silver, MD, Denise Hermann, MD Lynne
Warner Stevenson, MD
Executive Council: Arthur M. Feldman, MD, PhD,
President, Jay N. Cohn, MD Bertram Pitt, MD, Gary S.
Francis, MD Marc A. Silver, MD, Barry Greenberg, MD
Edmund Sonnenblick, MD, Marvin A. Konstam, MD
John Strobeck, MD, PhD, Carl Leier, MD Richard
Walsh, MD, Beverly H. Lorell, MD Salim Yusuf, MBBS,
PhD, Milton Packer, MD
Phamacotherapy : 2000, 20(5):495-522
Emphasis is placed on:
 the results of well-designed and adequately
controlled clinical trials (Strength of Evidence
= A)
 other useful investigations, including cohort
studies (Strength of Evidence = B).
 Expert opinion is the basis for a
recommendation (Strength of Evidence = C).
Phamacotherapy : 2000, 20(5):495-522
ß-blocker therapy
Recommendation :
 ß-blocker therapy should be routinely
administered to clinically stable patients with
left ventricular systolic dysfunction (left
ventricular ejection fraction less than or equal
to 40%) and mild to moderate heart failure
symptoms (ie, NYHA class II-III, Appendix A)
who are on standard therapy, which typically
includes ACE inhibitors, diuretics as needed to
control fluid retention, and digoxin (Strength of
Evidence = A).
Phamacotherapy : 2000, 20(5):495-522
ß-blocker therapy
Recommendation :
 There is insufficient evidence to recommend
the use of ß-blocker therapy for inpatients or
outpatients with symptoms of heart failure at
rest (ie, NYHA class IV) (Strength of Evidence
= C).
Phamacotherapy : 2000, 20(5):495-522
ß-blocker therapy
Recommendation :

ß-blocker should be initiated at low doses and
uptitrated slowly, no sooner than at 2-week
intervals.
 Patients who develop worsening heart failure
or other side effects require adjustment of
concomitant medications. May also require a
reduction in ß-blocker dose or a temporary or
permanent withdrawal of this therapy
(Strength of Evidence = B).
Phamacotherapy : 2000, 20(5):495-522
Digoxin
Recommendation :

Digoxin should be considered for patients
who have symptoms of heart failure (NYHA
class II-III, Strength of Evidence = A and
NYHA class IV, Strength of Evidence = C)
while receiving standard therapy.
Phamacotherapy : 2000, 20(5):495-522
Digoxin
Recommendation :

In the majority of patients, the dosage of
digoxin should be .125 mg to .25 mg daily
(Strength of Evidence = C).
 Target dose of digoxin should be lower than
traditionally assumed.
Phamacotherapy : 2000, 20(5):495-522
Digoxin
Recommendation :
In patients with heart failure and atrial fibrillation
with a rapid ventricular response, the
administration of high doses of digoxin (greater
than .25 mg) for rate control is not recommended.
 When necessary, additional rate control should be
achieved by the addition of ß-blocker therapy or
amiodarone (Strength of Evidence = C).

Phamacotherapy : 2000, 20(5):495-522
Anticoagulation
Recommendation :
 All patients with heart failure and atrial
fibrillation should be treated with warfarin
(goal INR : 2.0 to 3.0) unless contraindicated
(Strength of Evidence = A).
Phamacotherapy : 2000, 20(5):495-522
Anticoagulation
Recommendation :

Warfarin anticoagulation merits consideration
for patients with left ventricular ejection
fraction of 35% or less. Careful assessment
of the risks and benefits of anticoagulation
should be undertaken in individual patients
(Strength of Evidence = B).
Phamacotherapy : 2000, 20(5):495-522
Antiplatelets
Recommendation :

Currently, there is insufficient evidence
concerning the potential negative therapeutic
interaction between ASA and ACE inhibitors to
warrant withholding either of these medications
in which an indication exists (Strength of
Evidence = C).
Phamacotherapy : 2000, 20(5):495-522
ACE inhibitors
Recommendation

ACE inhibitors rather than ARBs continue to
be the agents of choice for blockade of the
renin angiotensin system in heart failure, and
they remain the cornerstone of standard
therapy for patients with left ventricular
systolic dysfunction with or without
symptomatic heart failure (Strength of
Evidence = A).
Phamacotherapy : 2000, 20(5):495-522
Antiarrhythmic Therapy
Recommendation :

Amiodarone is not recommended for the
primary prevention of death in patients with
chronic heart failure (Strength of Evidence =
A).
Phamacotherapy : 2000, 20(5):495-522
ICD
Recommendation :

patients with heart failure resuscitated from
primary ventricular fibrillation or who have
experienced hemodynamically destabilizing
sustained ventricular tachycardia be treated
with ICDs (Strength of Evidence = B).
Phamacotherapy : 2000, 20(5):495-522
Antiarrhythmic therapy
Recommendation :

Amiodarone is the preferred drug when
antiarrhythmic therapy is indicated in patients
with heart failure for supraventricular
tachycardia not controlled by digoxin or ßblocker or for patients with life-threatening
ventricular arrhythmia who are not candidates
for ICD placement (Strength of Evidence =
B).
Phamacotherapy : 2000, 20(5):495-522
Aldosterone Antagonists
Recommendation :



Spironolactone at low dose (ie, 12.5 mg to 25 mg
once daily) should be considered for patients
receiving standard therapy who have severe heart
failure (with recent or current NYHA class IV).
Potassium level (less than 5.0 mmol/L) and adequate
renal function (creatinine less than 2.5 mg/dL)
(Strength of Evidence = A).
Serum potassium should be monitored after the first
week and at regular intervals (Strength of Evidence =
A).
phamacotherapy : 2000, 20(5):495-522