Transcript RALES: Study Design

RALES: Study Design
NYHA III* or IV heart failure
LVEF 35%
ACE-I + loop diuretic ± digoxn
Aldactone®
25 mg/day
(n = 822)
3 years
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
RALES
All-Cause Mortality
RALES
Combined Endpoint of Cardiac
Mortality or Cardiac Hospitalization
RALES
6
Potassium
5
4.24 4.21
4.53
4.25
4.57
4.34
4
Baseline
Week 8
160
140
120
100
80
60
40
20
0
Month 24
110 114
Week 8
110 113
Month 24
Spironolactone
90
Systolic B.P.
160
Heart Rate
86
150
82
140
130
110 109
Baseline
Placebo
170
Creatinine
122 123
123 122
124 122
120
81 81
80
79
78
78 78
74
110
70
100
Baseline
Week 8
Month 24
Baseline
Week 8
Month 24
RALES
Adverse Events
Gynecomastia or
Breast Pain (Males)
15
Serious Hyperkalemia
( 6.0 mmol/L)
15
p <0.001
10%
10
5
p = NS
10
5
1%
1.2%
0
1.7%
0
P
S
P
Pitt et al, N Engl J Med, 1999.
Placebo
S
Spironolactone
RALES
Conclusion
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)