1. NYHA III* or IV heart failure ACE-I + loop diuretic ± digoxn
RALES: Study Design
NYHA III* or IV heart failure
LVEF £ 35%
ACE-I + loop diuretic ± digoxn
3 years
Aldactone® 25 mg/day
(n = 822)
Placebo
(n = 841)
Primary Endpoint
Total mortality
Secondary Endpoint
Cardiac mortality
Cardiac hospitalization
Cardiac mortality or cardiac hosptitalization
Changes from baseline in NYHA classification
Pitt et al, N Engl J Med, 1999.
*History of NYHA IV within 6 months before first dose

2. RALES All-Cause Mortality

3. Combined Endpoint of Cardiac Mortality or Cardiac Hospitalization
RALES
Combined Endpoint of Cardiac Mortality or Cardiac Hospitalization

4. RALES Potassium Creatinine Systolic B.P. Heart Rate 6 160 140 114 120
110
113
109
110
110
100 5 80
4.53
4.57 60
4.34 40
4.24
4.21
4.25 20 4
Baseline
Week 8
Month 24
Baseline
Week 8
Month 24
Placebo
Spironolactone
170 90
Systolic B.P.
Heart Rate
160 86
150 81 81
140 82 80 79 78 78
130
122
123
123
124
122
122 78
120 74
110
100 70
Baseline
Week 8
Month 24
Baseline
Week 8
Month 24

5. Gynecomastia or Breast Pain (Males)
RALES Adverse Events
Gynecomastia or Breast Pain (Males)
Serious Hyperkalemia (³ 6.0 mmol/L) 15 15
p <0.001
p = NS
10% 10 10 5 5
1.7% 1%
1.2% P S P S
Pitt et al, N Engl J Med, 1999.
Placebo
Spironolactone

6. RALES Conclusion All-cause mortality 30% (p<0.001)
Spironolactone used in conjunction with an ACE inhibitor provides significant beneifts in the treatment of advanced heart failure by reducing the risk of:
All-cause mortality 30% (p<0.001)
Cardiac mortality 31% (p<0.001)
Hospitalization for heart failure 35% (p<0.001)