Effective Care of the Heart Failure Patient The Five Step Plan

1
Effective Careof the Heart Failure PatientThe
Five Step Plan

• Jonathan Sackner-Bernstein, MD
• Clinical Scholars Program
• North Shore University Hospital
• Manhasset, New York
• Potential conflicts
• GlaxoSmithKline, AstraZeneca, Before It Happens
  To You

2
First Step

• Optimize volume status.

3
Optimizing Volume

• Diuretics
• Inotropes
• Vasodilators
• Ultrafiltration

4
Second Step

• Slow disease progression.

5
Slow Disease Progression

• ACE inhibition
• Beta-blockade
• Aldosterone antagonism
• Angiotensin receptor blockade
• Biventricular Pacemaker

6
Third Step

• Determine effectiveness.

7
Are Treatments Improving Outcomes?

• Men Women
• Probabilityof survival
• Time (years)
• Levy, NEJM, 2002

1.0 0.8 0.6 0.4 0.2 0.0
Risk ?12 per decade p 0.01
Risk ?12 per decade p 0.02
0 2 4 6 8 10
0 2 4 6 8 10
1990s
1980s
1970s
8
Fourth Step

• Reevaluate treatment goals.

9
Classification of Heart Failure (AHA/ACC)

• Stage Description
• A at high risk- HTN, CAD, DM, FH (age gt50)
• B structural heart disease no signs or
  symptoms
• C current or prior symptoms of HF
• D marked symptoms of HF at rest despite
  maximal therapy
• Circ 2001

10
Definition of Evidence-Based Medicine

• Application of scientific and clinical
  information to the development of preventative,
  diagnostic and therapeutic plans.
• Sources of information should be hierarchical
• Randomized Clinical Trials
• Controlled mechanistic studies
• Prospective observational studies
• Epidemiology
• Case series
• Clinical experience

11
Preventive Cardiology Standard of Care

• Lifestyle modifications
• BP lt 140/90
• lt 135/85 for HF or renal insufficiency
• lt 130/80 for DM
• LDL Cholesterol lt 100 (or lt 130, lt 160)
• HgA1c lt 7
• ASA (75 325 mg daily)
• ACE inhibitors (coronary or vascular disease)
• Beta-Blockers (post-MI and ACS patients)

Smith et al, Circulation 2001
12
Evidence or Guidelines?

• How big are the risks?
• What are the optimal treatment targets?
• What are the optimal tools?
• Are drugs within a class interchangeable?

13
Evidence or Guidelines?

• How big are the risks?

14
Current Diagnostic and Treatment Strategies
Advocate Minimal Interventions in Low-Risk
Patients

• Are low-risk patients safe?

15
Calculating Risk from Framingham Scores

• 52 year old man without diabetes, no history of
  hypertension, who does not smoke.
• Lipids
• Cholesterol 224
• HDL 39
• LDL 148

16
Calculating Risk from Framingham Scores

• Risk
• MI within 1 year 0.8
• Death within 1 year of MI 0.2

http//hin.nhlbi.nih.gov/atpiii/evalData.asp
17
Calculating Risk from Framingham Scores

• 56 year old woman, non-smoker, without diabetes,
  but with borderline blood pressure of 142/80.
• Lipids
• Cholesterol 232
• HDL 49
• LDL 153

18
Calculating Risk from Framingham Scores

• Risk
• MI within 1 year 0.4
• Death within 1 year of MI 0.1

http//hin.nhlbi.nih.gov/atpiii/evalData.asp
19
The Risk of Cardiac Death is HighWhat Action is
Recommended?

• Risk of death from MI within 1-2 years
• 52 yo man 1 in 500
• 56 yo woman 1 in 1,000
• Compare to lifetime risks of death from
• a car accident 1 in 6,500
• bad medical care 1 in 83,000
• an airplane crash 1 in 659,000
• Recommendations
• 52 yo man aspirin lifestyle change
• 56 yo woman lifestyle change
• Walsh J, True Odds 1998, NCEP/ATP-3, JNC-7

20
Atherosclerosis Starts by Our 20s

• Aorta Right Coronary Artery
• Prevalence
• ()
• n 204
• PDAY Study

21
Coronary Disease is Likely by Middle Age
Prevalence of CAD Using IVUS ()

• Tuzcu Circ 2001

22
Coronary Disease Is a Bigger Risk than Breast
Cancer Even in Young Women
12,000
Coronary Heart Disease
10,000
8,000
Prevalence (per 100,000)
6,000
4,000
Breast Cancer
2,000
0
30
40
50
60
70
Age (years)
National Cancer Institute and American Heart
Association
23
Advanced Heart Failure is More Common Than
Colo-rectal Cancer Even in Middle Age
10,000
8,000
Incidence Per 100,000
6,000
4,000
2,000
0
Age (years)
Heart Failure (Stage C/D)
Colorectal Cancer

• Kannel, Am Ht J, 1991, NCI, SEER, 2001

24
Evidence or Guidelines?

• How big are the risks?
• What are the optimal treatment targets?

25
Cardiac Risk Factors Standard Teaching

• Age
• Sex
• Family History
• Hypertension
• Hypercholesterolemia
• Smoking
• Diabetes
• Obesity (sedentary lifestyle)

26
Risks of Cardiovascular Disease are Increased
Even If You Are Only a Little Overweight

• 10 20
• Overweight

20 30 Overweight
J Chronic Diseases, 1978
27
Lifestyle Management The Ornish Way

• Vegetarian diet, stress management and yoga in
  patients with symptoms refractory to medical
  therapy, using treatments from 1970s
• Studies show
• 48 patients enrolled in randomized phase, less
  than ¾ completed study
• Completers showed significant regression of
  coronary atherosclerosis, less angina and lower
  risk of revascularization MI
• JAMA, 1998

28
The DASH Feeding Plan
NEJM 1997
29
The Lifestyle Evidence

• Exercise, weight loss, stress reduction have
  modest impact.
• Therapeutic lifestyle change improves well-being
  and quality of life
• No studies define the impact on the risk of MI,
  CVA or risk of death.
• Quitting smoking has major impact, but is very
  difficult.

30
The Lifestyle Myth

• People cant change, so recommending lifestyle
  will rarely do much good.
• Even if someone can change, it has little effect.

31
Cardiac Risk Factors Practical Approach

• Scientifically Patients Easily
• Cant Change Wont Change Modifiable
• Your genes Smoking Blood pressure
• (family history) Sedentary lifestyle Cholesterol
• Gender Obesity/overweight Diabetes
• Age

32
What is Optimal Blood Pressure?

• JNC-7
• Optimal blood pressure
• Target is 115/75
• Target blood pressure
• Goal is lt 140/90
• Target for diabetics and those with renal
  insufficiency
• Target is 130/80

33
Evidence for Blood Pressure Targets

• 1950s Risk lowest for BP lt 120/80
• 1970s Risk lowest for BP lt 118/77
• 2001 Risk lowest for BP lt 120/80
• 2003 Risk lowest for BP lt 115/75

34
Higher Risk of MI, CVA or CV Death in
Prehypertension (above 120/80)

• Women

Men
Normal 120-130 Systolic
High Normal 130-139 Systolic
Normal 120-130 Systolic
High Normal 130-139 Systolic
Vasan, NEJM, 2001
35
Goal Blood Pressure Should Be 115/75

• Cause Ages Death Relative Risk
• Stroke
• 40-49 414 0.36 (0.32-0.40)
• 50-59 1372 0.38 (0.35-.040)
• 60-69 2939 0.43 (0.41-0.45)
• 70-79 4327 0.50 (0.48-0.52)
• 80-89 2636 0.67 (0.63-0.71)
• IHD
• 40-49 1022 0.49 (0.49-0.53)
• 50-59 5594 0.50 (0.49-0.52)
• 60-69 10450 0.54 (0.53-0.55)
• 70-79 10852 0.60 (0.58-0.61)
• 80-89 5649 0.67 (0.64-0.70)
• Prospective Studies Collaboration, Lancet 2003

0.25 0.35 0.5 0.7 1.0
36
What is Optimal Blood Pressure?

• JNC-7
• Optimal blood pressure
• Target is 115/75
• Target blood pressure
• Goal is lt 140/90
• Target for diabetics and those with renal
  insufficiency
• Target is 130/80

• Optimal
• 115/75 or
• at least 20/10 reduction

37
What is Optimal LDL-Cholesterol?

• ATP-3/NCEP
• Coronary Heart Disease
• Target is 100 mg/dl
• 2 Risk Factors
• Target is 130 mg/dl
• 0-1 Risk Factors
• Target is 160 mg/dl

38
Good LDL Levels Do Not Minimize Risk
3.0
2.5
Risk of MI, CABG or Angioplasty
Women
2.0
1.5
Men
1.0
0.5
70
100
130
160
190
LDL Level
ARIC Study, 10 yr follow-up of 45-64 year olds
39
Lower LDL Targets Minimize Risk

• Coronary Events at 1 Year
• Based on Level of LDL
• (4S trial)

25 20 15 10 5 0
Per Cent Coronary Events
77 96 116 135 154 174
LDL Level Measured
4S Investigators
40
Aggressive Management Reverses Plaques
Effects of Pravastatin and Atorvastatin in the
REVERSAL Study

• Nissen, AHA 2003

Pravastatin (lt 130)
Atorvastatin (lt 80)
41
Optimal LDL Lowering Minimizes Risk
Prove-It
Event
Time (months)
NEJM 2004
42
What is Optimal LDL-Cholesterol?

• ATP-3/NCEP
• Coronary Heart Disease
• Target is 100 mg/dl
• 2 Risk Factors
• Target is 130 mg/dl
• 0-1 Risk Factors
• Target is 160 mg/dl

• Optimal
• Target lt 100 mg/dl or
• High risk lt 80 mg/dl

43
What is Optimal HgA1c Target?

• ADA
• 7

44
Diabetic Complications Relate to HgA1c Level
Triple
Risk of Complications Compared to risk if HgA1c lt
6
Double
5
6
7
8
9
10
Glycohemoglobin ()
Before It Happens To You
45
Do All Beta-Blockers Effect Glucose Metabolism
Equally?
Diabetic Hypertensives
0.4

0.2
Hg A1c
0
-0.2
-0.4
Carvedilol
b1 Selective Agent (Atenolol, Metoprolol)

• Giugliano, Ann Intern Med. 1997, Jacob et al. J
  Hypertens. 1998

46
COMET Risk of New Onset Diabetes
Incidence New Diabetes
25

• Carvedilol Metoprolol RR (CI) p
• 122/1151 149/1147 0.78 0.04
• (10.6) (13) (0.61,0.99)

HR 0.78 (0.61, 0.99) p 0.04
20
15
10
5
0
0
1
2
3
4
5
Time (years)
Poole-Wilson, Lancet 2003
47
What is Optimal HgA1c Target?

• ADA
• 7

• Optimal
• 6

48
Treatment Targets

• Guideline Evidence-Based
• Recommendations Goals
• Blood Pressure lt140/90 lt 115/75
• (JNC-7) (minimum ? 20/10)
• LDL lt 160, 130, 100 lt 100, 80
• (NCEP/ATP-3)
• HgA1c lt 7 lt 6
• (ADA)

49
Fifth Step

• Define and implement the plan.

50
Evidence or Guidelines?

• How big are the risks?
• What are the optimal treatment targets?
• What are the optimal tools?

51
All Patients Should Receive ACE Inhibitors
Time (years)
NEJM 2000, 1993, 1993, 1987
52
ACE Inhibition Reduces Risk in Diabetics and
Those with Vascular Disease
Effect of Ramipril in HOPE
25
20
with event
15
10
5
0
N Engl J Med, 2000
53
ACE Inhibition Reduces Risk in CAD
Placebo
Perindopril
54
All Patients Should Receive Beta-blockers

• CAPRICORN
• (n 1959)

Time (years)
Lancet 2001, NEJM 1996, Lancet 1999, NEJM 2001
55
Beta-Blockers Reduce Risk of Sudden Death
10
Risk ? 26
Risk ? 40
Risk Sudden Death
Risk ? 28
Risk ? 56
5
Risk ? 30
0
US Carvedilol
Merit-HF
MAPPHY (HTN)
Copernicus
BHAT
Placebo Beta-blocker

• Am J Hypertension 1991, JAMA 1993,NEJM 1996,
  Lancet, 1999

56
COMET Effect on Composite Endpoints

• Death Death Death CV Death Death
• All Hosp CV Hosp Xplant, MI, HF MI, HF, UA,
  Arrhy HF

80
80
80
80
80
60
60
60
60
60
40
40
40
40
40

• Risk
• 12
• p 0.013

• Risk
• 7
• p 0.097

• Risk
• 10
• p 0.022

• Risk
• 6
• p 0.12

• Risk
• 11
• p 0.019

20
20
20
20
20
0
0
0
0
0
Time ( months)
57
COMET Mode of Death
58
Patients Benefit from Aldosterone Antagonism
Risk of Death
Placebo Aldosterone Antagonist

• NEJM 1999, 2002

59
Effect of Candesartan in Heart Failure
Cause-Specific Mortality
All-cause Mortality
30
30
CV Risk ? 13 p 0.006
Risk ? 10 p 0.032
CV
20
Cumulative Incidence ()
20
10
10
Non-CV
0
0
0
1
2
3
4
0
1
2
3
4
Time (years)
Time (years)

• CHARM, Lancet 2003

60
Biventricular Pacing and Defibrillator Therapies
Reduce Heart Failure Progression
from Feldman Bristow ACC 2003
61
Statins Reduce Risk of MI, CVA and Death
Independent of Baseline LDL Level
LDL Level Before Starting on Statin Therapy
Before It Happens To You
62
Safety of Simvastatin in HPS

• Parameter Simvastatin Placebo
• n 10,269 10,267
• Liver Function
• 24x ULN 139 (1.35) 131 (1.28)
• gt4x ULN 43 (0.42) 32 (0.31)
• Elevated CK
• 410x ULN 19 (0.19) 13 (0.13)
• gt10x ULN 11 (0.11) 6 (0.06)
• Myopathy
• No rhabdomyolysis 5 (0.05) 1 (0.01)
• Rhabdomyolysis 5 (0.05) 3 (0.03)
• Lancet 2002

63
Its Too Late for Primary Prevention

• By 50,
• 85 of us have lipid-laden atheromas in our
  arterial walls.
• Over 50 have LDL gt 100
• Over 50 have BP gt 120/80

64
Evidence or Guidelines?

• How big are the risks?
• What are the optimal treatment targets?
• What are the optimal tools?
• Are drugs within a class interchangeable?

65
Are Drugs Within a Class Interchangeable?

• ACE inhibitors?

• Benazepril Placebo p
• n 300 283
• Death 8 1 0.04
• Sudden Death 3 1
• MI 3 0
• Pulmonary Embolus 1 0
• Variceal Bleed 1 0

Benazepril Placebo p n 300 283 Death 8 1 0.04 Sud
den Death 3 1 MI 3 0 Pulmonary Embolus 1 0 Varicea
l Bleed 1 0
AIPRI Study, NEJM 1996
66
Are Drugs Within a Class Interchangeable?
Risk of Death
Risk of New Diabetes

• ACE inhibitors? Perhaps not.
• Beta-blockers in HF?

40
Risk ? 17 p0.0017
Risk ? 22 p 0.04
40
30
30
20
20
prolong life 1.4 yrs
10
10
0
0
0
1
2
3
4
5
0
1
2
3
4
5
Time (years)
Metoprolol
Carvedilol
67
Are Drugs Within a Class Interchangeable?

• Timolol Propranolol Metoprolol
• Norwegian BHAT LIT
• (n1884) (n3837) (n2395)

• ACE inhibitors? Perhaps not.
• Beta-blockers in HF? No.
• Beta-blockers post-MI?

Cumulative Mortality Rate
68
Are Drugs Within a Class Interchangeable?
Prove-It

• ACE inhibitors? Probably not.
• Beta-blockers in HF? No.
• Beta-blockers post-MI? No.
• Statins for dyslipidemia?

Event
Time (months)
69
Are Drugs Within a Class Interchangeable?

• ACE inhibitors? Probably not.
• Beta-blockers in HF? No.
• Beta-blockers post-MI? No.
• Statins for dyslipidemia? No.

70
The Challenge

• Consider what the patient expects and wants
• Reiteration of our standard approaches?
• Patients want optimized care, based on risks and
  benefits for them.

71
Its Too Late for Primary Prevention

• By 50,
• 85 of us have lipid-laden atheromas in our
  arterial walls.
• Over 50 have LDL gt 100
• Over 50 have BP gt 120/80

72
Targets and Tools to Deliver Optimal Care

• Targets
• Blood pressure of 115/75
• LDL of 100 (or lt 80 in high risk)
• HDL of 40 (men) or 50 (women)
• HgA1C of 6 (unless hypoglycemia)
• Tools (make optimal selections)
• ACE inhibitors, beta-blockers and diuretics
• Statins
• Aspirin

73
Clinical Goals are ParamountEvidence Defines
Best Practices

• Scientifically based optimal care will minimize
  risk.

Scientifically based strategies to minimize the
risk of a heart attack or stroke. This book will
save lives. Valentin Fuster, MD, PhD