The RAVEL Study
A RAndomised (double blind) study with the Sirolimus
coated BX™ VElocity balloon expandable stent
(CYPHER™) in the treatment of patients with De Novo
native coronary artery Lesions
M.C. Morice, P.W Serruys, J.E. Sousa, J. Fajadet, M. Perin, E. Ban Hayashi, A.
Colombo, G. Schuler, P. Barragan, C. Bode
on behalf of the RAVEL Study Group.
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RAVEL: Background
• Sirolimus (Rapamune® - Wyeth Ayerst) is a naturally
occurring macrocyclic antibiotic
• It is a potent immunosuppressive agent inducing late G1
cell cycle arrest
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Results of the RAVEL Trial
Bx velocity™ stent coated with Sirolimus™ (Cypher™) versus placebo
Inclusion Criteria
• Single de novo lesions
•
•
Native coronary arteries <18mm in length
Native coronary arteries 2.5 to 3.5mm in diameter
Design:
•
•
•
Double-blinded, placebo-controlled, randomized trial
Enrolled 237 patients from several countries in Europe and Latin America
All patients received Clopidogrel for a 2-month period
Results:
•
•
•
•
•
There was no case of restenosis in patients receiving the Sirolimus coated stent
Rate was 26% in the uncoated stent group
Late lumen loss of only 0.01mm with Sirolimus coated stent
No reported cases of subacute thrombosis in patients treated with the Sirolimus
coated stent
Event-free survival was 97% with Sirolimus coated stent
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RAVEL: Study Design
237 patients with single de novo lesions in native coronary arteries < 18 mm in length
and 2.5 to 3.5 mm in diameter, randomized trial in Europe and Latin America to
Uncoated BX Velocity Stent
(n=118)
BX Velocity Stent Coated with
Sirolimus (n=120)
+
+
Clopidogrel for 2 months
Clopidogrel for 2 months
Major Adverse Cardiac Events (MACE) (Death / MI / Urgent TVR)
Angiographic study
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RAVEL: Baseline Characteristics
Diabetes
60
P=NS
Diabetes (%)
16%
15%
10%
Unstable Angina (%)
50
20%
15
P=NS
48
40
Lesion Length (mm)
25%
21%
Lesion Length
Unstable Angina
10
20
P=NS
9.6
9.6
N=118
N=120
5
5%
N=118
N=120
0%
Bare Stent
Sirolimus
Coated
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N=118
N=120
0
Bare Stent
0
Sirolimus
Coated
Bare Stent
Sirolimus
Coated
RAVEL: Minimum Lumen Diameter (mm)
P = NS
2.50
2.50
2.41
P< 0.0001
2.43
P< 0.0001
2.42
2.5
0.9
0.8
1.50
1.00
0.95
0.94
0.50
2.00
1.50
1.00
0.50
2
1.64
1.5
1
Late Loss (mm)
P = NS
Post MLD (mm)
Pre MLD (mm)
2.00
Follow-up MLD (mm)
0.8
0.7
0.6
0.5
0.4
0.3
0.2
0.5
0.1
0.00
0.00
0
0.01
0
Bare
Sirolimus
Bare
Sirolimus
Bare
Sirolimus
Bare
Sirolimus
Stent
Coated
Stent
Coated
Stent
Coated
Stent
Coated
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RAVEL: Results
P<0.0001
P<0.001
25%
20%
15%
10%
5%
0%
0%
Bare Stent
Sirolimus
Coated
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30%
P<0.001
26
%
100%
25%
MACE Free Survival (%)
Angiographic Restenosis (%)
26%
Target Vessel Revascularization (%)
30%
MACE Free
TVR
Restenosis
20%
15%
10%
5%
80%
73
%
97
%
60%
40%
20%
0%
0%
Bare Stent
0%
Sirolimus
Coated
Bare Stent
Sirolimus
Coated
RAVEL: Long-Term Results At 1 year
MACE Free
Restenosis
P<0.001
P<0.001
30%
100%
1 Year MACE Free Survival (%)
Angiographic Restenosis (%)
26%
25%
20%
15%
10%
5%
80%
94%
71%
60%
40%
20%
0%
0%
0%
Bare Stent
Sirolimus
Coated
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Bare Stent
Sirolimus
Coated
RAVEL: QCA Results in Diabetic Patients
Late Loss
Restenosis
P<0.001
P<0.001
42%
1.00
40%
0.82
Late Lumem Loss (mm)
Angiographic Restenosis (%)
45%
35%
30%
25%
20%
15%
10%
0.80
0.60
0.40
0.20
0.08
5%
0%
0%
0.00
Bare Stent
Sirolimus
Coated
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Bare Stent
Sirolimus
Coated
RAVEL: Cautionary Notes
• In the First In Man study of 45 patients followed over 45
months, there was one stent thrombosis between months
12 and 13
• While data is available to just over 6 months, more long
term data is needed to exclude a risk of late thrombosis
• Fortunately, no aneuryms or pseudoaneurysms have
been observed with 2 year follow-up in the First In Man
study (FIM)
• RAVEL may be underpowered to demonstrate late safety
signals, the ongoing SIRIUS trial enrolling 1101 patients at
53 centers will provide more information in this regard
• The efficacy of coated stenting in the management of in
stent restenosis has not been studied to date
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RAVEL : Conclusions
The treatment of a de novo lesion with CYPHER™ appears
feasible and safe : no acute, subacute (30 days) or late
occlusion occurred although clopidogrel / ticlopidine was
administered for only 2 months
Virtual elimination of neo-intimal in-stent proliferation: MLD
post deployment (2.43 mm) remains essentially unchanged
at 6 months (2.42 mm) with no measurable late loss (-0.05
mm) Restenosis (0%) and no evidence of edge effect
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RAVEL: Conclusions
Angiographic results are confirmed in a subset of patients
evaluated with IVUS: Percentage of volume obstruction of
the stent is less than 2%, No evidence of negative
remodelling at the edges of the stent.
This virtual elimination of neo-intimal hyperplasia was
shown to be clinically translated into an absence of reintervention so that event free survival at 6 months is close
to 97% and significantly (P<0.0001) superior to the 72%
event free survival of the patients treated with the bare
stent.
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