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Prevention is the Best TreatmentPrevention is the Best Treatment
Marc A. Pfeffer, MD, PhDMarc A. Pfeffer, MD, PhDDzau Professor of Medicine, Harvard Medical SchoolDzau Professor of Medicine, Harvard Medical SchoolCardiovascular Division, Brigham & Women’s HospitalCardiovascular Division, Brigham & Women’s Hospital
Boston, MassachusettsBoston, Massachusetts
Disclosures: Marc A. Pfeffer, M.D., Ph.D., reports having serves as consultant to Aastrom, Abbott Vascular, Amgen, Cleveland Clinic, Concert, Daiichi Sankyo, Fibrogen, Genzyme, GlaxoSmithKline, Hamilton Health Sciences, Medtronic, Merck, Novartis, Novo Nordisk, Roche, Salix, Sanderling, Sanofi Aventis, Servier, and Teva and having received grant support from Amgen, Celladon, Novartis, and Sanofi-Aventis. The Brigham and Women’s Hospital has patents for the use of inhibitors of the renin-angiotensin system in survivors of MI with Novartis. Dr. Pfeffer’s shares are irrevocably transferred to charity.
NORMAL
No symptomsNormal exerciseNormal LV
No symptomsNormal exerciseAbnormal LV
No symptoms ExerciseAbnormal LV
Symptoms ExerciseAbnormal LV
with treatmentSymptoms not controlled
AsymptomaticLV Dysfunction
Compensated HF
Decompensated Heart failure
Refractory HeartFailure
Stage A
Stage B
Stage C
Stage DNYHA Class (I–IV)
NYHA IV
Stage C
2001
Effects of Treatment on Morbidity in HypertensionVA Cooperative Study Group on Antihypertensive Agents
143 men (DBP 115 to 129 mm Hg), mean follow-up ~18 months, 29 events
Placebo group(n=70)
HCTZ + Reserpine + Hydralazine HCl group
(n=73)Total events 27 2 Deaths (all CV) 4 0 Class A events* 10 0 Other treatment failures 7 1
Class B events† 6 1 CHF 4 0
*
Required treatment with known active agents and permanent removal from protocol assigned
therapy (nature of events included dissecting aortic aneurysm, sudden death, ruptured AAA,
fundi striate hemorrhage and papilledema, CHF, elevated BUN, rehospitalization,
cerebrovascular accident, and others)†
Did not require permanent discontinuation of protocol treatments (nature of events included MI,
CHF, cerebrovascular thrombosis, and TIA
VA Cooperative Study Group. JAMA 1967;202(11);1028-33
42 Randomized Controlled Trials
Low-Dose Diuretics vs Placebo
CHDCHF
StrokeCVD events
CVD mortality
Total mortality
0.79 (0.69-0.92)0.51 (0.42-0.62)0.71 (0.63-0.81)0.76 (0.69-0.83)0.81 (0.73-0.92)
0.90 (0.84-0.96)
0.002<0.001<0.001<0.001
0.001
0.002
Outcome
RR (95% CI)
p-value
Favors low-dose diuretics
Favorsplacebo
0.4 0.6 0.8 1.0 1.2 1.4Relative Risk
2003
Antihypertensive Rx CHF
SHEP Cooperative Research Group. JAMA 1991;265:3255–64Dahlöf B et al. Lancet 1991;338:1281–5
SHEP
n
2365
2371
0.46
CHF
48
102
(0.33 to 0.65)
STOP
n
812
815
0.49
CHF
19
36
Active
Placebo
Relative
risk
Fatal or Nonfatal Stroke Heart Failure
HR = 0.70(0.49-1.01)
HR = 0.36(0.22-0.58)
Target blood pressure 150/80 mmHg
The Trial: International, multi centre, randomised double-blind placebo controlledInclusion Criteria: Aged 80 or more,Systolic BP; 160 -199mmHg+ diastolic BP; <110 mmHgPrimary Endpoint: All strokes (fatal and non-fatal)
2008
Lewis EF. JACC 2003;42(8):1446-53
CARE: Multivariable Predictors ofHeart Failure
PEACE: Development of HF
Age 65 to <75 years (vs <65)
1.89 (1.4 - 2.5)
<0.00
Age ≥75 years (vs <65)
3.15 (2.2 - 4.5)
<0.00
Hx of Diabetes
2.10 (1.6 - 2.7)
<0.00
Body Mass Index (>30 kg/m2)
2.09 (1.5- 3.0)
<0.00
Current smoker
1.86 (1.3 - 2.6)
<0.00
Hx of Stroke/TIA
1.82 (1.3 - 2.6)
<0.00
eGFR (ml/min/m2) <60
1.67 (1.3 - 2.2)
<0.00
Hx of Hypertension
1.62 (1.3 - 2.1)
<0.00
Hx of CABG
1.58 (1.2 - 2.0)
<0.00
LVEF 40–50% (vs ≥50)
1.40 (1.0 - 1.9)
0.03Angina Symptom (CCS)
1.40 (1.1 - 1.8)
0.009Hx of Myocardial Infarction
1.39 (1.1 - 1.8)
0.01Randomization to Trandolapril
0.73 (0.57-0.93)
0.01
Lewis EF et al. Circulation: Heart Failure 2009;2:209-16
Baseline Characteristics
HR (95% CI)
p-value
Placebo n = 228/2223 (10.3%)Simvastatin n = 184/2221 (8.3%)p <0.015
Stages of HF and treatment options for systolic heart failure
Jessup M and Brozena S. N Engl J Med 2003
ICD
Risk factor reduction, patient and family education
Treat hypertension, dyslipidemia, diabetes. ACE inhibitors (or ARB) in selected patients
ACE inhibitors (or ARB) in all patients; Beta blockers in selected patients.
1’ Prevention
NORMAL
No symptomsNormal exerciseNormal LV
No symptomsNormal exerciseAbnormal LV
No symptoms ExerciseAbnormal LV
Symptoms ExerciseAbnormal LV
with treatmentSymptoms not controlled
AsymptomaticLV Dysfunction
Compensated HF
Decompensated Heart failure
Refractory HeartFailure
Stage A
Stage B
Stage C
Stage DNYHA Class (I–IV)
NYHA IV
Stage C
2001
Years following MI0 2 4 6 8 10 12 14 16 18 20
Cupples et al. The Framingham Study. NIH Publication 1987;87:2703
MI male
Cum
ulat
ive
prob
abili
ty
of e
vent
The Framingham Heart Study: 1987Risk of Heart Failure After MI
(Age 35 to 94 at Diagnosis)
0
0.1
0.2
0.3
0.4
0.5
MI femaleMatched maleMatched female
1992
The
SAVETrial
Mortality and CHF MorbidityMortality and CHF Morbidity1992
The
SAVETrial
All-Cause Mortality
Years
Pro
babi
lity
of E
vent
0
0.05
0.1
0.15
0.2
0.25
0.3
0 1 2 3
0.35
0.4
4
ACE-I
Placebo
ACE-I299522501617892223
Placebo297121841521853138
OR: 0.74 (0.66–0.83)
ACE-I: 702/2995 (23.4%)
Placebo: 866/2971 (29.1%)
4
TRACEEchocardiographicEF £ 35%
AIREClinical and/or radiographic signs of HF
SAVERadionuclideEF £ 40%2000
Flather, Yusuf, Kober, et al.
LV DysfunctionLV Dysfunction(Progressive)(Progressive)
MI
Asymptomatic
Remodeling
SymptomaticCHF
Sudden Ischemic Sudden Pump failure
50
40
30
20
10
00 6 12 18 24 30 36 42 48
p=0.0036
Months
Mortality (%)
PlaceboEnalapril
Treatment
P=NSPrevention
1992
1991
2003
1 2 3 4 5
14
12
10
8
6
4
2
Follow-Up (Years)
%
Heart Failure or Death
Heart Failure
HR Death post-HF = 9.8 (95% CI 7.7 – 13.5)
HF: 68 of 243 (28%) died within 3.5 years
Vs.
No HF: 252 of 3617 (7%) died within 5 years
2003
CARECARE
2003
ICD
Risk factor reduction, patient and family education
Treat hypertension, dyslipidemia, diabetes. ACE inhibitors (or ARB) in selected patients
ACE inhibitors (or ARB) in all patients; Beta blockers in selected patients.
1’ Prevention
Stages of HF and treatment options for systolic heart failure
Jessup M and Brozena S2003
2009
80
90
100
110
120
130
140
150
160
170
198619871988198919901991199219931994199519961997199819992000200120022003
Year
Firs
t Hos
pita
lizat
ion
rate
(p
er 1
00,0
00 p
opul
atio
n)
Men Women
2009
Superior doctors prevent the disease.Mediocre doctors treat the disease before evident.Inferior doctors treat the full blown disease.
- Huang Dee: Nai-Ching (2600 B.C. 1st Chinese Medical Text.)
Stages of HF and treatment options for systolic heart failure
Jessup M and Brozena S. N Engl J Med 2003
ICD
Risk factor reduction, patient and family education
Treat hypertension, dyslipidemia, diabetes. ACE inhibitors (or ARB) in selected patients
ACE inhibitors (or ARB) in all patients; Beta blockers in selected patients.
1’ Prevention
Heart FailureHeart Failure
Sustained Hyperfunction
·Congenital· Valvular·Hypertension
· Idiopathic·Nutritional· Infectious·Autoimmune· Toxic· Infiltrative
Loss of Contractile
Tissue
Ischemic Coronary
Artery Disease
Myopathic and Interstitial Processes
GENETICSGENETICS