Prevention is the Best Treatment Prevention is the Best Treatment - - PowerPoint PPT Presentation

Prevention is the Best Treatment Prevention is the Best Treatment

Marc A. Pfeffer, MD, PhD Marc A. Pfeffer, MD, PhD

Dzau Professor of Medicine, Harvard Medical School Dzau Professor of Medicine, Harvard Medical School Cardiovascular Division, Brigham & Women’s Hospital Cardiovascular Division, Brigham & Women’s Hospital Boston, Massachusetts Boston, 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 symptoms Normal exercise Normal LV No symptoms Normal exercise Abnormal LV No symptoms Exercise Abnormal LV Symptoms Exercise Abnormal LV with treatment Symptoms not controlled

Asymptomatic LV Dysfunction

Compensated HF Decompensated Heart failure Refractory Heart Failure Stage A Stage B Stage C Stage D

NYHA Class (I–IV) NYHA IV

Stage C 2001

Effects of Treatment on Morbidity in Hypertension

VA 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 Class A events* 10 Other treatment failures 7 1 Class B events† 6 1 CHF 4

* 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

CHD CHF Stroke CVD 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 Favors placebo 0.4 0.6 0.8 1.0 1.2 1.4 Relative Risk

2003

Antihypertensive Rx CHF

SHEP Cooperative Research Group. JAMA 1991;265:3255–64 Dahlöf 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 controlled Inclusion Criteria: Aged 80 or more, Systolic BP; 160 -199mmHg + diastolic BP; <110 mmHg Primary Endpoint: All strokes (fatal and non-fatal)

2008

Lewis EF. JACC 2003;42(8):1446-53

CARE: Multivariable Predictors of Heart 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) 0.03 Angina Symptom (CCS) 1.40 (1.1 - 1.8) 0.009 Hx of Myocardial Infarction 1.39 (1.1 - 1.8) 0.01 Randomization 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 symptoms Normal exercise Normal LV No symptoms Normal exercise Abnormal LV No symptoms Exercise Abnormal LV Symptoms Exercise Abnormal LV with treatment Symptoms not controlled

Asymptomatic LV Dysfunction

Compensated HF Decompensated Heart failure Refractory Heart Failure Stage A Stage B Stage C Stage D

NYHA Class (I–IV) NYHA IV

Stage C 2001

Years following MI 2 4 6 8 10 12 14 16 18 20

Cupples et al. The Framingham Study. NIH Publication 1987;87:2703

MI male

Cumulative probability

• f event

The Framingham Heart Study: 1987

Risk of Heart Failure After MI

(Age 35 to 94 at Diagnosis) 0.1 0.2 0.3 0.4 0.5

MI female Matched male Matched female

1992

The

SAVE

Trial

Mortality and CHF Morbidity Mortality and CHF Morbidity

1992

The

SAVE

Trial

All-Cause Mortality

Years Probability of Event

0.05 0.1 0.15 0.2 0.25 0.3 1 2 3 0.35 0.4 4

ACE-I Placebo

ACE-I 2995 2250 1617 892 223 Placebo 2971 2184 1521 853 138

OR: 0.74 (0.66–0.83) ACE-I: 702/2995 (23.4%) Placebo: 866/2971 (29.1%)

4

TRACE

Echocardiographic EF £ 35%

AIRE

Clinical and/or radiographic signs

• f HF

SAVE

Radionuclide EF £ 40%

2000

Flather, Yusuf, Kober, et al.

LV Dysfunction LV Dysfunction (Progressive) (Progressive)

MI Asymptomatic Remodeling Symptomatic CHF Sudden Ischemic Sudden Pump failure

50 40 30 20 10 6 12 18 24 30 36 42 48 p=0.0036 Months Mortality (%) Placebo Enalapril

Treatment

P=NS

Prevention 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

CARE CARE

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 S 2003

2009

80 90 100 110 120 130 140 150 160 170

198619871988198919901991199219931994199519961997199819992000200120022003

Year First Hospitalization rate (per 100,000 population)

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 Failure Heart Failure

Sustained Hyperfunction

· Congenital · Valvular · Hypertension · Idiopathic · Nutritional · Infectious · Autoimmune · Toxic · Infiltrative

Loss of Contractile Tissue

Ischemic Coronary Artery Disease

Myopathic and Interstitial Processes

GENETICS GENETICS