SOFA - Discussant

Hot Line Session II
5 September 2005 11.00- 12.30
ESC Congress - Stockholm
DISCUSSANT
Prof. Luigi Tavazzi
S. Matteo University Hospital
Pavia, Italy

Primary ICD Prevention Studies
• 7 RCTs involving 5139 patients
• 2 year follow-up:
- 3% reduction of absolute risk of death :
17.3% vs 14.3% (annual 1.5%)
Moss AJ Circulation 2005; 111: 2542

Secondary ICD Prevention Studies
• 3 RCTs involving 2963 patients
• 2 year follow-up:
- 7.5% reduction of absolute risk of death:
23% vs 15.5% (annual : 3.7%)
Moss AJ Circulation 2005; 111: 2542

The problem of sudden death prevention
• ICDs saved lives; but most patients implanted do
not benefit from ICDs
• The number of patients at risk of sudden death is
much broader than that of cardiac patients
implanted/implantable with ICDs

Mortality
0.4
0.3
0.2
0.1
0
SCD-HeFT trial: Mortality results
HR 97.5% Cl P-
Value
Amiodarone vs. Placebo 1.06 0.86, 1.30 0.529
ICD Therapy vs. Placebo 0.77 0.62, 0.96 0.007
0 6 12 18 24 30 36 42 48 54 60
Months of follow-up
Amiodarone
ICD Therapy
Placebo
ACC, 2004

The problem of sudden death
Solutions?
• Need to refine the identification of patients at
very high risk of sudden arrhythmic death (to
be implanted with ICDs)
• Need of drugs effective in the prevention of
arrhythmic death (n-3 PUFA?)

0%
-5% 5%
-10% 10%
-15% 15%
-20% 20%
-25% 25%
-30% 30%
-35% 35%
-40% 40%
-45% 45%
-50% 50%
-15% 15%
Effect of n-3 PUFA treatment in
GISSI-Prevenzione (11.323 post-MI pts)
Death
CV Death
Non-fatal Non fatal AMI
Non-fatal Non fatal AMI
Non-fatal Non fatal stroke
Non-fatal Non fatal stroke
p

No. Deaths / No. Patients
EF (%) n-3 PUFA Control
> 50
46-50
41-45
= 40
Total
GISSI-Prevenzione trial
38/2627
16/954
6/563
28/677
88/4821
37/2679
25/919
24/568
47/643
133/4809
Test for Trend, 2P = 0.0170
Sudden Death
0.0 0.5 1.0 1.5 2.0
Treatment better Treatment worse
Macchia A et al. Eur J Heart Fail 2005; 5: 904-9
HR (95% CI)
0.89 (0.46-1.69)
0.39 (0.15-1.02)
0.19 (0.06-0.56)
0.55 (0.29-1.04)
0.53 (0.36-0.76)
2P
0.7108
0.0546
0.0028
0.0666
0.0007

% patients with VT/VF
Portland trial in 200 ICD patients:
No reduced risk of VT/VF
90
80
70
60
50
40
30
20
10
0
fish oil placebo
P=0.19 P=0.007
all patients VT at entry
Raitt et al. 2005

SOFA trial
Cox proportional hazards for all patients and
subgroups
VT at entry
VF at entry
Prior MI
EF < 30% at entry
All patients
0.2 0.5 1 2 4
Hazard Ratio (95% CI)

FAAT Trial
Alexander Leaf, personal communication, ESC Munich, August 30th 2004
Cumulative Proportion of Time to First Event
Fish oil (n.200)
---- Olive oil (n.202)
Fish oil (n. 114)
---- Olive oil (n.119)
Intention to treat
Compliers
p=0.003
Months
p=0.02
A
B

Conclusions
• Beneficial effect of n-3 PUFA on life-threatening
cardiac arrhythmias in post MI patients has
been reasonably demonstrated
• In ICD patients (of any etiology) non consistent
findings (just a positive trend)
• No significant side-effects (which is extremely
important in pts at high risk of collateral effects)
• Further research warranted

R1
R2
GISSI-HF trial
7057 HF pts
n-3 PUFA Placebo
1 g daily
4642 pts
Rosuvastatin Placebo
10 mg daily
Mean follow-up 3 years
Expected end of trial : 2007