SUCCESS WITH FAILURE in 2003

1
SUCCESS WITH FAILURE in 2003
in BC

• Andrew Ignaszewski MD FRCPC
• Heart Function Clinic and
• Heart Transplant Program
• St. Pauls Hospital
• Vancouver BC

2
Outline

• Burden of CHF
• Neurohormonal theory - recent developments
• Recent advances in diagnosis of CHF
• BNP
• Recent advances in treatment of CHF
• medical
• team management
• BC Heart Failure Care - guidelines
• Future plans - how can we do it in BC in 2003

3
Heart Failure Problem
Better survival of patients with coronary
disease and hypertension
Aging of population
Heart Failure population becoming larger, older,
and frailer

• classic paradox
• improvement in one area of medicine leads to
  increases in diseases in another

4
CHF Mortality 1950-2000
Framingham Heart Study
N Engl J Med 20023471397
5
CHF in BC - 2001
Th Failing Heart, BC MHS, Nov 2002

• 40,945 patients with CHF
• at least as many have CHF that is not yet
  diagnosed
• 12,651 admissions for CHF
• admission rate of 31
• 100,459 hospital days
• estimated LOS 7.9 days
• estimated cost 90,423,100
• 7148 per admission

6
CV Mortality in BC - 2001
Th Failing Heart, BC MHS, Nov 2002
All CVD
IHD
7
CHF Mortality in BC - 2001
Th Failing Heart, BC MHS, Nov 2002
8
BC CHF Survival 2001
Th Failing Heart, BC MHS, Nov 2002
9
CHF Medication Utilization in BC - 2001
Th Failing Heart, BC MHS, Nov 2002
10
Evolving Models of CHF
Cardiorenal Digitalis and diuretic to perfuse
kidneys
Hemodynamic Vasodilators or positive inotropes to
relieve ventricular wall stress
Neurohormonal ACE inhibitors, beta blockers, and
other agents to block neurohormonal activation
1940s 1960s 1970s 1990s2000
Pepper, Arch Intern Med 1999.
11
Neurohormonal System - Center CV Risk
Sudden death
Atherosclerosis
HTN
Diabetes
Neurohormonal System
Stroke
LVH
MI
HF
ESRD
ESRD End-stage renal disease, HF Heart
failure, HTN Hypertension LVH Left
ventricular hypertrophy, MI Myocardial
infarction
12
Neurohormonal System in CHF

• BNP
• Angiotensin II
• Norepinephrine
• Aldosterone
• Endothelin
• Vasopressin

13
Natriuretic Peptides
14
BNP vs. NYHA Classification
Triage BNP Test Package Insert

12.3 95.4 221.5 459.1
1006.3 (pg/mL)
15
BNP Levels of Patients Without CHF, With Baseline
LV Dysfunction, and With CHF
N139 N14 N97
Dao, Q., Maisel, A. et al. J. American College of
Cardiology, Vol 37, No. 2, 2001
16
BNP Levels in Patients With Dyspnea Secondary to
CHF or COPD
N56 N94
Dao, Q., Maisel, A. et al. J. American College of
Cardiology, Vol 37, No. 2, 2001
17
BNP Levels in Patients With Edema Diagnosed With
CHF or Without CHF
N44 N44
Dao, Q., Maisel, A. et al. J. American College of
Cardiology, Vol 37, No. 2, 2001
18
Plasma BNP Concentration
Survival in CHF Patients With LV Dysfunction
BNP lt 73 pg/ml
100
80
plt 0.0001
Cumulative Survival ()
60
40
BNP gt 73 pg/ml
20
0
Months
0
10
20
30
40
50
Tsutamoto T. et al. Circulation 199796509-516
19
Mortality Reduction with ACEi
50 40 30 20 10 0
54
ACE Inhibitor Control
40
39
35
Mortality ()
25
23
20
17
Enalapril 20 mg bid p0.003
Enalapril 10 mg bid plt0.0036
Captopril50 mg tid p0.019
Ramipril 5 mg bid p0.002
Follow up times were 6 and 12 months 48
months 6 months. The CONSENSUS Trial Study
Group. N Engl J Med 19873161429-1435. The SOLVD
Investigators. N Engl J Med 1991325293-302. The
SAVE Investigators. N Engl J Med
1992327669-677. AIRE Investigators. Lancet
1993342821-828.
20
ACE Inhibitors - Hospitalization Benefit
Benzapril, Cilazapril, Penndopril Adapted from
Garg R. et al. JAMA 19952731450-1456.
21
Use of ACEi for Treatment of Heart Failure

• Introduce as soon as safely possible
• Following acute MI, unless contraindicated or not
  tolerated, for 6 weeks, or indefinitely in those
  with LVEF lt 40 or clinical evidence of CHF
• All asymptomatic patients with LVEF lt 35-40,
  unless contraindicated or not tolerated
• All patients with symptomatic CHF, NYHA Class
  II-IV unless contraindicated or not tolerated
• Target dose should be either the dosage used in
  trials or maximum tolerated dose

Canadian Cardiovascular Society Guideline Update
for the Management Prevention of CHF 2001.
22
ACEI Indicated for HF in BC
23
Prognostic Value of Neurohormonal Activation
Plasma Norepinephrine Levels in Patients with CHF
1.0
PNE lt400 pg/mL
PNE 400-800 pg/mL
0.8
PNE gt800 pg/mL
0.6
Probability of Survival ()
0.4
0.2
0
0
10
20
30
40
50
60
Elapsed Time in Months
N Engl J Med 1984311819-823
24
MOCHA - Effect of Carvedilol on LVEF
p?0.05 vs. placebo. plt0.0001 vs. placebo

plt0.001


??LVEF (EF units)
Placebo
25 mg bid
6.25 mg bid
12.5 mg bid
Carvedilol
Patients receiving diuretics, ACE inhibitors,
digoxin follow-up 6 months placebo (n84),
carvedilol (n261). Multicenter Oral Carvedilol
Heart Failure Assessment. Adapted from Bristow
MR, et al. Circulation. 19969428072816.
25
All-cause mortality
Beta blockers in CHF
26
COPERNICUS
Survival
All-cause mortality
100
90
Carvedilol
80
Placebo
70
60
Nominal p0.00014 35 risk reduction
50
24
0
20
16
12
8
4
28
Months
.
27
Major Clinical Trials with Beta-blockers with
Heart Failure
Canadian Cardiovascular Society Guideline Update
for the Management Prevention of CHF 2001.
28
Principal RCTs of ? Blockers in CHF
Entry Criteria
Minimum
Minimum
Stable
Open-label
Minimum LVEF
systolic BP
heart rate
(weeks)
challenge
(units)
(mmHg)
(bpm)
MDC
stable
4
40
90
45
CIBIS-I
6 (3)
4
40
100
65
4
ANZ
4
45
90
50
US carvedilol
8 (4)
4
35
85
68

CIBIS-II
6
35
100
60

MERIT-HF
2
40
100
68
29
Effect of Carvedilol on Risk of a Clinical Event
in Subgroups Defined by Baseline SBP
All-cause Mortality
85-95 mm Hg
Interaction p0.64
96-105 mm Hg
106-115 mm Hg
116-125 mm Hg
gt 125 mm Hg
Death or CHF hospitalizations
Interaction p0.80
Hazard Ratio
0
0.2
0.4
0.6
0.8
1
1.2
1.4
30
Change in Heart Rate and CHF Mortality
Change in mortality ()
60
PROFILE
40
XAMOTEROL
PROMISE
20
VHeFT (Prazosin)
0
CIBIS
VHeFT (HDZ/ISDN)
-20
SOLVD
BHAT
-40

NOR TIMOLOL
CONSENSUS
ANZ
-60
US CARVEDILOL
-80
MOCHA

GESICA
-100
-20
-16
-12
-8
-4
0
4
8
12
Change in heart rate (bpm)
Kjekshus Gullestad (1999)
31
Target Doses and Outcomes in Trials of Beta
Blockers
Effect onMortality
Dose Range(mean dose)
Metoprolol

MDC1
100150 mg (108 mg)
No ?
(tartrate)
MERIT-HF2
200 mg (159 mg)
? 34
(succinate)
Bisoprolol
5 mg (3.8 mg)
CIBIS3
NS
10 mg (7.5 mg)
CIBIS II4
? 34
plt0.01. The combined endpoint of mortality
and need for transplantation was significantly
reduced. 1. MDC Trial Study Group. Lancet.
199334214411446. 2. MERIT-HF Study Group.
Lancet. 199935320012007. 3. CIBIS
Investigators. Circulation. 19949017651773. 4.
CIBIS II Investigators. Lancet. 1999353913.
32
Recommendations for the Use of Beta-blockers in
Heart Failure

• All NYHA class II-III HF and LVEF ? 40, unless
  contraindicated to reduce mortality,
  hospitalizations, and to improve cardiac function
  and quality of life
• Patients with stable class IV HF
• Patients who are NYHA class I asymptomatic with
  LV systolic function with LVEF ? 40,
  particularly
• post-MI

Canadian Cardiovascular Society Guideline Update
for the Management Prevention of CHF 2001.
33
Beta-Blocking Drugs for HF in BC
34
CHF Disease Management
Control Volume Slow Disease Progression

Diuretic
RAAS Inhibition
Beta-Blockade
Treat residual symptoms
DIGOXIN
SPIRONOLACTONE
Am J Cardiol 199983(suppl 2A)9A-38A
35
Diuretics Used in HF in BC
BC HF Guideline draft April 23,03
36
Medical Therapy for CHF
ARB? VPI? BNP?
40
ACEI
30
Mortality
Beta-blockers
20
Spironolactone
10
???
1970
1980
1990
2000
37
Heart Failure Care
BC HF Guideline draft April 23,03
38
Heart Failure Care
BC HF Guideline draft April 23,03
39
Algorithm for Heart Failure Neurohormonal
Inhibiting Drug Therapy
Heart Failure (digoxin, diuretics as indicated)
ACE-I
Tolerated
Not tolerated
Add beta blocker
ARB
Tolerated
Tolerated
Not tolerated
Follow-up
Beta blocker
ARB
Follow-up
Follow-up
40
Cognitive Function and CHF

• What people know about their disease

Patients
41
Heart Failure- Cause for Hospital Admission
Other
Non compliance
Ischemia
Arrhythmia
Volume overload
0
10
20
30
40
of Patients
42
HFC - Specific Objectives

• To reduce mortality and morbidity
• To reduce costs of care through a decrease in
  hospital admissions and readmissions
• To improve quality of life
• To educate patients to take an active role in
  their treatment and management of CHF
• To develop a data management system to track
  clinical outcomes and costs per case within the
  in-patient and HFC
• Additionally, a clinic was envisioned that would
• be physician directed, nurse managed
• be structured to address the gap between current
  community-based CHF services and the
  pre-assessment for transplantation
• develop an integrated clinical pathway for
  in-patient, out-patient, and community care to
  ensure continuity of care and to decrease the
  duplication of service.

43
SPH HFC - Patient Education Rates
82
81.4
81.5
81.5
81.5
81.5
81
80.5
79.7
Education
80
Visits which include
Percentage of Patient
79.5
79
78.5
Disease
Medication
Fluid/Salt
Monitor
Exercise
Weight
Education Type
44
(No Transcript)
45
Mortality
HFC 2001
HFC 2000
BC 2000/2001
Indicator
7
6
20 - 30
Mortality Rate
46
Hospital Admission
HFC 2001
HFC 2000
BC 2000/2001
Indicator
7
6
31
Admission Rate
47
Effects of Adding ?-Blockers or Angiotensin
Receptor Blockers vs Increasing ACE Inhibitor
Dose in HF
Symptoms Hospitalization Mortality Increase
dose No ? 12 8 NS of ACE inhibitor1 effect Ad
d angiotensin Improvement ? 27 No receptor
blocker2 effect Add ?-blockade3
Improvement ? 20-35 ? 35
vs. low dose ACE Not recommended for patients
receiving ACEI and ?-blockade. vs.
recommended ACE dosage. 1. Packer M et al.
Circulation. 199910023122318. 2. Cohn JN et
al. N Engl J Med. 20013451667-1675. 3. Lechat P
et al. Circulation. 19989811841191.
48
Conclusion

• CHF is common
• CHF is deadly
• CHF is costly
• CHF is preventable
• effective strategies exist to deal with CHF but
  are greatly underutilized