Transcript VBWG06_DataAlert_HF (10 slides

Heart failure: The national burden
VBWG
• Affects 1 million Americans
• >550,000 new cases annually
• >53,000 deaths in 2002
• Leading Medicare hospital diagnosis
• >1 million hospitalizations annually
• Direct and indirect costs: $27.9 billion
AHA. Heart disease and stroke statistics–2005 update.
Koelling TM et al. Am Heart J. 2004;147:74-8.
ACC/AHA: Heart failure stages A and B
VBWG
Stage A
Stage B
Definition
No structural heart
disease/asymptomatic
Structural heart
disease/asymptomatic
Patients
Hypertension
CAD
Diabetes
Obesity
Metabolic syndrome
Previous MI
LV remodeling
LV hypertrophy
Low EF
Goals
Treat BP, lipids
Smoking cessation
 Regular exercise
 Alcohol/drug use
All measures under
stage A
Therapy
ACEI or ARB for vascular
disease/diabetes*
ACEI or ARB*
-Blockers*
*Appropriate patients
Hunt SA et al. J Am Coll Cardiol. 2005;46:1-82.
ACC/AHA: Heart failure stages C and D
VBWG
Stage C
Stage D
Definition
Structural heart disease
Prior/current symptoms
Refractory HF
Patients
Shortness of breath
Fatigue
Exercise capacity
Marked symptoms at rest despite
maximal therapy
Goals
All Stage A and B
Dietary salt restriction
All Stage A, B, and C
Decision re: appropriate level of care
Drug
therapy
Routine drugs
Diuretics
ACEI
-Blockers
Options
Compassionate care/hospice
Selected patients
Aldosterone antagonist
ARBs
Digitalis
Hydralazine/nitrates
Devices*
Extraordinary measures
Heart transplant
Chronic inotropes
Permanent mechanical support
Experimental surgery/drugs
Biventricular pacing
Implantable defibrillators
*Selected patients
Hunt SA et al. J Am Coll Cardiol. 2005;46:1-82.
VBWG
CHARM: HF patients with LV dysfunction
CHARM-Alternative
CHARM-Added
Patients
N = 2028
LVEF ≤40%
Intolerant to ACEI
N = 2548
LVEF ≤40%
Treated with ACEI
Therapy
Candesartan 32 mg/d
vs placebo
Candesartan 32 mg/d vs placebo
+ ACEI and other HF therapy
Follow-up
41 months
33.7 months
Primary
outcome*
23% RRR (P < 0.001)
7% absolute 
15% RRR (P < 0.011)
4% absolute 
*CV mortality/HF hospitalization
RRR = relative risk reduction
Granger CB et al. Lancet. 2003;362:772-6.
McMurray JJV et al. Lancet. 2003;362:767-71.
VALIANT: Study design
VBWG
Patients
N = 14,703 with MI within ≤10 days
HF and/or LVEF <35%*
Therapy
Valsartan 160 mg 2/d (n = 4909)
Captopril 50 mg 3/d (n = 4909)
Captopril 50 mg 3/d + valsartan 80 mg 2/d (n = 4885)
Follow-up
24.7 months
*<40% by radionuclide ventriculography (RVG)
Pfeffer MA et al. N Engl J Med. 2003;349:1893-906.
VALIANT: Primary outcome—
Death from any cause
VBWG
0.4
Valsartan*
Valsartan plus captopril†
Captopril
0.3
Probability
0.2
of event
0.1
0.0
0
*P = 0.98 vs captopril
†P = 0.73 vs captopril
6
12 18 24 30 36
Months
Pfeffer MA et al. N Engl J Med. 2003;349:1893-906.
VBWG
ACC/AHA recommendations:
ARBs in patients with LV dysfunction
Class
Alternative therapy:
Use ARBs approved for the treatment
of HF in patients witih current or prior HF
symptoms who are ACEI intolerant
ARBs are reasonable alternatives to ACEI as
first-line therapy for patients with mild to
moderate HF, especially those already taking
ARBs for other indications
ARBs should be administered to post-MI
patients without HF symptoms who are
intolerant of ACEIs and have a low LVEF
Added therapy:
Consider adding ARBs in persistently
symptomatic patients with reduced LVEF who
are already treated with conventional therapy
Level of evidence
I
A
IIa
A
I
B
IIb
B
Hunt SA et al. J Am Coll Cardiol. 2005;46:1-82.
CHARM-Added: Effects of adding
candesartan to -blocker and ACEI
VBWG
Candesartan
Placebo
223/702
260/574
274/711
264/561
0.14
Recommended dose
of ACE inhibitor
Yes
232/643
No
251/633
275/648
263/624
0.26
All patients
538/1272
-Blocker
Yes
No
483/1276
Candesartan
better
Placebo
better
P*
0.6 0.7 0.8 0.9 1.0 1.1 1.2
Hazard ratio
*For treatment interaction
McMurray JVV et al. Lancet. 2003;362:767-71.
VBWG
HF with LV dysfunction:
Patients, efficacy, and dosing considerations
Efficacy
Initial
dose(s)
Maximum
dose(s)
ARB
Patients
Candesartan
HF
CV mortality
 HF hospitalizations
4–8 mg
1/d
32 mg
1/d
Valsartan
HF
Post-MI
 CV mortality
20–40 mg
2/d
160 mg
2/d
Adapted from Hunt SA et al. J Am Coll Cardiol. 2005;46:1-82.
VBWG
CHARM: Prevention of diabetes
with candesartan
12
10
8
Proportion
of patients
(%)
Placebo
RRR = 22%
HR = 0.78 (0.64–0.96)
P = 0.020
6
n = 202 (7.4%)
n = 163 (6.0%)
4
Candesartan
2
0
0
1.0
2.0
3.0
3.5
Years
RRR = relative risk reduction
Yusuf S et al. Circulation. 2005;112:48-53.