1. Eric J Robinson, M.D. Cardiologist April 25, 2015
PARADIGM-HF Trial
Eric J Robinson, M.D.
Cardiologist
April 25, 2015

17. PARADIGM-HF: Pre-specified endpoints
Primary: Cardiovascular death or heart failure hospitalization
Cardiovascular death
Heart failure hospitalization
Secondary:
Death from any cause
KCCQ (CSS - symptoms and physical limitations)
New onset atrial fibrillation
Decline in renal function

18. PARADIGM-HF Prospective comparison of ARNI with ACEI to Determine Impact on Global Mortality and morbidity in Heart Failure trial
Death from any cause
16% risk reduction 40
HR: 0.84 (0.76, 0.93)
P = 30
Enalapril
(n=4212)
835
LCZ696
(n=4187)
711
Cumulative Proportion of Patients
Who Died from Any Cause (%) 20 10
180
360
540
720
900
1080
1260
Days after Randomization

19. PARADIGM-HF: Effect of LCZ696 vs
PARADIGM-HF: Effect of LCZ696 vs. enalapril on other secondary endpoints
LCZ696
(n=4187)
Enalapril
(n=4212)
Treatment
effect P
Value
KCCQ clinical summary score at 8 months
- 2.99
± 0.36
- 4.63
1.64
(0.63, 2.65)
0.001
New onset
atrial fibrillation
84/2670
(3.1%)
83/2638
Hazard ratio
0.97
(0.72,1.31)
0.83
Protocol-defined decline in renal function*
94/4187
(2.2%)
108/4212
(2.6%)
0.86
(0.65, 1.13)
0.28
*1) ESRD or 2) a decrease ≥50% in eGFR from value at randomization or 3) a decrease in eGFR >30 ml/min/1.73 m2 to <60 ml/min/1.73 m2

20. PARADIGM-HF: Percentage of patients with at least 5 points deterioration in KCCQ scores at month 8%
(N=3833) (N=3873)
P=0.004
P=0.029
P<0.001
P<0.005
P<0.001
P<0.001
P=0.001
P=0.001
P<0.001
P<0.001
Clinical summary score based on the physical limitation and total symptom score domains.
Death imputed as zero. The analysis included all patients with at least one KCCQ data point

21. PARADIGM-HF: Physician assessment
Change in NYHA functional class
from baseline to month 8
LCZ696
N=3833* n (%)
Enalapril
N=3825* n (%)
P-value
Improved
639 (16.7)
569 (14.9)
0.0015
Unchanged
2989 (78.0)
2990 (78.2)
Worse
205 (5.4)
266 (7.0)
*Surviving patients with data (deaths excluded)

22. PARADIGM-HF: Treatment failure*
*Addition of a new drug for treatment of WHF, need for IV therapy or increase in diuretic dose >1 month
HR 0.84 (0.74, 0.94)
p =
Enalapril
(%)
LCZ696
Proportion of patients

23. PARADIGM-HF: ED/ER visits for HF
Enalapril
LCZ696
Proportion of patients
Number of ER visits*
(%)
HR 0.66 (0.52, 0.85)
p = 0.001
RR 0.70 (0.52, 0.94)
p = 0.017
Patients visiting ED
ED Visits
*Includes repeat episodes

24. PARADIGM-HF: Hospitalization for HF
Enalapril
LCZ696
Proportion of patients
Number of admissions*
(%)
HR 0.79 (0.71, 0.89)
p =
RR 0.77 (0.67, 0.89)
p =
Patients hospitalized
Hospitalizations
*Includes repeat episodes

25. PARADIGM-HF: Intensive care management
Intensive management in hospital
LCZ696
N=4187 n (%)
Enalapril
N=4212 n (%)
P-value
Number of patients requiring intensive care
551
624
0.87 (0.78, 0.98)
P=0.019
Total number of stays in intensive care
768
879
0.82 (0.72, 0.94)
P=0.005
Patients receiving IV positive inotropic drugs
161
229
0.69 (0.57, 0.85)
P < 0.001

26. PARADIGM-HF: Devices and surgery for worsening HF
Patients with CRT implantation, VAD insertion or heart transplantation
LCZ696
N=4187 n (%)
Enalapril
N=4212 n (%)
P-value
CRT
CRT-D
54 (1.3)
77 (1.8)
0.052
CRT-P
34 (0.8)
31 (0.7)
0.710
VAD/transplant
VAD
12 (0.29)
19 (0.45)
0.280
Transplant
1 (0.02)
4 (0.09)
0.375

27. PARADIGM-HF: Hospitalization for any cause
Enalapril
LCZ696
Proportion of patients
Number of admissions*
HR 0.88 (0.82, 0.94)
p < 0.001
RR 0.84 (0.78, 0.91)
p < 0.001
(%)
Patients hospitalized
Hospitalizations
*Includes repeat episodes

28. PARADIGM-HF: cause/ mode of death
All causes
CV causes
Sudden
WHF
Enalapril
LCZ696
Number HR
p =
0.84
< 0.001
0.80
0.0008
0.80
0.80
0.008
0.79
0.04