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 2001 Stage A Asymptomatic No symptoms Normal exercise LV Dysfunction Stage B Normal LV No symptoms Compensated HF Normal exercise Stage C Abnormal LV Decompensated No symptoms Heart failure Exercise Stage C Abnormal LV Refractory Heart Symptoms Exercise Failure Stage D NYHA Class Abnormal LV Symptoms not controlled (I–IV) with treatment NYHA IV

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 HCTZ + Reserpine + Placebo group Hydralazine HCl group (n=70) (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, VA Cooperative Study Group. JAMA 1967;202(11);1028-33 cerebrovascular accident, and others) † Did not require permanent discontinuation of protocol treatments (nature of events included MI, CHF, cerebrovascular thrombosis, and TIA

2003 Low-Dose Diuretics vs Placebo Favors low- Favors Outcome dose diuretics placebo CHD 0.79 (0.69-0.92) 0.002 RR (95% CI) CHF 0.51 (0.42-0.62) <0.001 Stroke 0.71 (0.63-0.81) <0.001 p-value CVD events 0.76 (0.69-0.83) <0.001 CVD mortality 0.81 (0.73-0.92) 0.001 Total mortality 0.90 (0.84-0.96) 0.002 0.4 0.6 0.8 1.0 1.2 1.4 Relative Risk 42 Randomized Controlled Trials

Antihypertensive Rx CHF Active Placebo SHEP Relative n 2365 risk 2371 SHEP Cooperative Research Group. JAMA 1991;265:3255–64 Dahlöf B et al. Lancet 1991;338:1281–5 0.46 CHF 48 102 (0.33 to 0.65) STOP n 812 815 0.49 CHF 19 36

2008 The Trial: International, multi centre, Target blood pressure randomised double-blind placebo controlled 150/80 mmHg Inclusion Criteria: Aged 80 or more, Systolic BP; 160 -199mmHg + diastolic BP; <110 mmHg Primary Endpoint: All strokes (fatal and non-fatal ) Fatal or Nonfatal Stroke Heart Failure HR = 0.70 HR = 0.36 (0.49-1.01) (0.22-0.58)

CARE: Multivariable Predictors of Heart Failure Lewis EF. JACC 2003;42(8):1446-53

PEACE: Development of HF Baseline Characteristics Age 65 to <75 years (vs <65) HR (95% CI) 1.89 (1.4 - 2.5) p-value <0.00 Age ≥75 years (vs <65) 3.15 (2.2 - 4.5) <0.00 Hx of Diabetes 2.10 (1.6 - 2.7) Lewis EF et al. Circulation: Heart Failure 2009;2:209-16 <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

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 1’ Prevention ICD ACE inhibitors (or ARB) in all patients; Beta blockers in selected patients. Treat hypertension, dyslipidemia, diabetes. ACE inhibitors (or ARB) in selected patients Risk factor reduction, patient and family education

NORMAL 2001 Stage A Asymptomatic No symptoms Normal exercise LV Dysfunction Stage B Normal LV No symptoms Compensated HF Normal exercise Stage C Abnormal LV Decompensated No symptoms Heart failure Exercise Stage C Abnormal LV Refractory Heart Symptoms Exercise Failure Stage D NYHA Class Abnormal LV Symptoms not controlled (I–IV) with treatment NYHA IV

The Framingham Heart Study: 1987 Risk of Heart Failure After MI (Age 35 to 94 at Diagnosis) 0.5 Cumulative probability MI male MI female 0.4 Matched male of event 0.3 Matched female 0.2 0.1 0 0 2 4 6 8 10 12 14 16 18 20 Years following MI Cupples et al. The Framingham Study. NIH Publication 1987;87:2703

The SAVE Trial 1992

The SAVE Mortality and CHF Morbidity Mortality and CHF Morbidity Trial 1992

SAVE AIRE TRACE Radionuclide Clinical and/or Echocardiographic 2000 EF £ 40% EF £ 35% radiographic signs of HF 0.4 All-Cause Mortality 0.35 0.3 Probability of Event Placebo 0.25 ACE-I 0.2 0.15 Placebo: 866/2971 (29.1%) 0.1 ACE-I: 702/2995 (23.4%) 0.05 OR: 0.74 (0.66–0.83) 0 Years 0 1 2 4 3 ACE-I 2995 Placebo 2250 2971 1617 Flather, Yusuf, Kober, et al. 2184 4 892 1521 223 853 138

LV Dysfunction LV Dysfunction (Progressive) (Progressive) Asymptomatic Remodeling MI Symptomatic CHF Sudden Ischemic Sudden Pump failure

1991 1992 Mortality (%) 50 Placebo Enalapril 40 Treatment p=0.0036 30 20 Prevention 10 P=NS 0 0 6 12 18 24 30 36 42 48 Months

2003

CARE CARE 2003 HR Death post-HF = 9.8 (95% CI 7.7 – 13.5) 14 HF: 68 of 243 (28%) died within 3.5 years 12 Vs. No HF: 252 of 3617 (7%) died within 5 years 10 % 8 6 4 2 1 2 3 4 5 Heart Failure or Death Follow-Up (Years) Heart Failure

2003

Stages of HF and treatment options for systolic heart failure 2003 Jessup M and Brozena S 1’ Prevention ICD ACE inhibitors (or ARB) in all patients; Beta blockers in selected patients. Treat hypertension, dyslipidemia, diabetes. ACE inhibitors (or ARB) in selected patients Risk factor reduction, patient and family education

2009 2009 170 160 First Hospitalization rate (per 100,000 population) 150 140 130 120 110 100 Men Women 90 80 198619871988198919901991199219931994199519961997199819992000200120022003 Year

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. 1 st Chinese Medical Text.)

Stages of HF and treatment options for systolic heart failure Jessup M and Brozena S. N Engl J Med 2003 1’ Prevention ICD ACE inhibitors (or ARB) in all patients; Beta blockers in selected patients. Treat hypertension, dyslipidemia, diabetes. ACE inhibitors (or ARB) in selected patients Risk factor reduction, patient and family education

Heart Failure Heart Failure GENETICS GENETICS Loss of Myopathic and Sustained Contractile Interstitial Hyperfunction Tissue Processes · Congenital · Idiopathic · Valvular · Nutritional Ischemic · Hypertension · Infectious Coronary · Autoimmune Artery Disease · Toxic · Infiltrative