1. חזק בהגנה לבבית Valsartan in Heart Failure
Valsartan Heart Failure Trial
ה –ARB הראשון שהוכיח תוצאות חיוביות באי-ספיקת לב ב – Mega Trial.

2. Study Overview
5010 patients 18 years; EF <40%; NYHA II-IV; LVIDd >2.9 cm/m2
Receiving background therapy
ACE inhibitors, diuretics, digoxin, -blockers
Randomized to
Val-HeFT, a randomized, double-blind, placebo-controlled study of 5010 HF patients with NYHA class II-IV, was an international collaboration in 16 industrialized countries at 300 centers
Patients continued on their standard background therapies, which included ACE inhibitors (n=4644, 92.7%), diuretics (n=4300, 85.5%), digoxin (n=3375, 67.3%), and -blockers (n=1784, 35.6%)
Patients were randomized to treatment with valsartan 40 mg bid titrated to 160 mg bid or placebo
The primary endpoints were combined all-cause mortality and morbidity and all-cause mortality
Patients were stratified to each arm according to whether they were on a -blocker or not
Study continued until 906 deaths were reported
Valsartan 40 mg bid titrated to 160 mg bid
Placebo
Cohn JN et al. Eur J Heart Fail. 2000;2:

3. Effect of Valsartan on Combined Morbidity/Mortality Endpoint*65 70 75 80 85 90 95
100
Valsartan
Placebo
13.2% Risk Reduction
P = 0.009
Probability of Event-Free Survival 3 6 9 12 15 18 21 24 27 30
Months
*All-cause mortality, sudden death with resuscitation, hospitalization for worsening heart failure, or therapy with IV inotropes or vasodilators.
Cohn JN et al. N Engl J Med. 2001;345:

4. HF-Related Hospitalizations*65 70 75 80 85 90 95
100
Valsartan
Placebo
Event-Free Probability
27.5% Risk Reduction
P < 0.001 3 6 9 12 15 18 21 24 27 30
Months
HF = heart failure.
Cohn JN et al. N Engl J Med. 2001;345:

5. Time Since Randomization (months)
Reduction in Combined Morbidity/Mortality Endpoint* with Valsartan (No ACE-I Subgroup)
Time Since Randomization (months) 40 50 60 70 80 90
100 3 6 9 12 15 18 21 24 27 30
P < 0.001
44.0% Risk reduction
Valsartan, n=185
Placebo, n=181
Probability of Event-Free probability
Hazard ratio (Cox model) : 0.560
*First morbid event, including death or hospitalization
Maggioni et al. J Am Coll Cardiol 2002;40:

6. Reduction in Mortality with Valsartan (No ACE-I Subgroup)
100
Valsartan, n=185 90
Placebo, n=181
Proportion Survived 80 70
33% Risk reduction 60
P = 0.017 50 3 6 9 12 15 18 21 24 27 30
Time Since Randomization (months)
Maggioni et al. J Am Coll Cardiol 2002;40:

7. Estimated probability of atrial fibrillation
Val-HeFT: Diovan® Significantly Reduces Incidence of Atrial Fibrillation Occurrence by 37%
0.15
Log rank test p=0.0001
0.10
Placebo (n=2499)
Estimated probability of atrial fibrillation
0.05
Diovan 160 mg (n= 2511) 2 4 6 8 10 12 14 16 18 20 22 24
Months of follow-up
Maggioni A et al. Am Heart J 2005;149:548–57