Transcript Document

ROTAXUS
A Prospective, Randomized Trial of
High-Speed Rotational Atherectomy Prior to
Paclitaxel-Eluting Stent Implantation in
Complex Calcified Coronary Lesions
Gert Richardt, MD, PhD
Herzzentrum
Segeberger Kliniken
Bad Segeberg, Germany
Disclosure Statement of Financial Interest
Within the past 12 months, I or my spouse/partner have had a financial
interest/arrangement or affiliation with the organization(s) listed below.
Affiliation/Financial Relationship
Company
•
•
Grant/Research Support
Consulting Fees/Honoraria
•
•
Boston Scientific
Boston Scientific, Cordis J&J,
Abbott Vascular, Medtronic
•
•
•
•
•
Major Stock Shareholder/Equity
Royalty Income
Ownership/Founder
Intellectual Property Rights
Other Financial Benefit
•
•
•
•
•
None
None
None
None
None
Background (I)
• DES have shown favourable results when implanted in
complex lesions and patients.
• Calcified coronary lesions can pose special problems, and may
prevent stent delivery or expansion and increase the likelihood
of stent thrombosis and/or restenosis.
• Calcified lesions may form a particular threat to DES, as
damage to the polymer/drug coating and inadequate diffusion
of the drug may decrease DES effectiveness.
Background (II)
• Rotational atherectomy can effectively modify calcified
plaques and facilitate stent delivery and expansion.
• However, rotablation causes additional vessel injury with
increased neointimal formation when used as a standalone therapy or combined with bare-metal stents.
• Elective rotablation followed by DES implantation can be
a rational complementary concept in complex calcified
lesions, but this is not supported by randomized
controlled studies.
Objective of the ROTAXUS trial
.. to evaluate whether routine rotablation
prior to PES implantation is more
effective than the standard of care
(stenting without rotablation) in the
setting of complex calcified coronary
artery disease.
ROTAXUS: Study Details
Design
- Prospective, randomized, active-controlled clinical trial
Participating Centers
- Heart Center, Segeberger Kliniken, Bad Segeberg, Germany
- Heart Center Bad Krozingen, Bad Krozingen, Germany
- University Hospital Hamburg-Eppendorf, Hamburg, Germany
Study Chair
Gert Richardt
Heart Center
Bad Segeberg, Germany
Principal Investigators
Mohamed Abdel-Wahab
Ahmed A. Khattab
Independent Data Safety and Monitoring Board
Independent QCA Core Lab (ISAR Research Center, Munich, Germany)
Independent Statistical Core Lab (Derek Robinson, Sussex, UK)
Inclusion Criteria
•
•
Clinical inclusion criteria
1.
Age above 18 years
2.
Angina and/or reproducible ischemia
3.
Informed written consent
Angiographic inclusion criteria
First degree criteria (all)
1.
De-novo lesion in a native coronary artery
2.
Moderate to severe calcification
Second degree criteria (at least one)
1.
Ostial location
2.
Bifurcational lesion
3.
Long lesion (≥ 15mm)
Exclusion Criteria
•
•
Clinical exclusion criteria
1.
Myocardial infarction within 4 weeks
2.
Left ventricular ejection fraction < 30%
3.
Limited long term prognosis
Angiographic exclusion criteria
1.
Unprotected left main lesions
2.
Coronary artery bypass graft stenoses
3.
In-stent restenoses
4.
Chronic total occlusions
5.
Target vessel thrombus
6.
Target vessel dissection
Endpoints
•
Primary endpoint
In-stent late lumen loss at 9 months
•
Secondary endpoints
1.
Major adverse cardiac events (MACE)
2.
Definite stent thrombosis
3.
In-segment late lumen loss
4.
In-segment binary restenosis
5.
Angiographic success
6.
Strategy success (angiogr. success without crossover or stent loss)
7.
Procedural duration
8.
Contrast amount
Sample Size Calculation
•
Hypothesis
Rotablation prior to paclitaxel-eluting stent treatment will be
superior to stenting without rotablation in reducing the late
lumen loss at 9 months
•
Assumption
Late loss (primary endpoint) will be reduced from 0.5 ± 0.5 mm
in the control group to 0.3 mm in the rotablation group
Power of 80%
One-sided alpha-level of 0.05
Random sequence 1:1
Needed total number of patients/lesions: 198
Analysis by intention-to-treat
ROTAXUS
240 patients enrolled between August 2006 and March 2010 at 3
clinical sites in Germany
1:1 randomization
Rota + PES
(N=120)
PTCA + PES
(N=120)
240 patients analyzed with complete in-hospital follow-up
- 2 patients died in-hospital
- 6 patients withdrew consent
- 5 patients lost at follow-up
Clinical follow-up at 9
months in 96.2% (N=227)
Angiographic follow-up at 9
months in 80.5% (N=190)
Baseline Characteristics (I)
Rota + PES
n = 120
PTCA + PES
n = 120
P
Value
Age (years)
70.5±8.2
71.8±7.2
0.20
Males
86 (72.3%)
96 (81.7%)
0.13
BMI (kg/m2)
27.9±4.3
27.8±4.0
0.68
Diabetes mellitus
33 (27.7%)
32 (26.8%)
0.88
Hypertension
106 (89.1%)
95 (79.8%)
0.05
Dyslipidemia
91 (76.5%)
87 (73.1%)
0.55
Current smokers
24 (20.2%)
16 (13.5%)
0.17
Family history of CAD
39 (32.8%)
44 (37.0%)
0.50
5 (4.2%)
8 (6.7%)
0.40
Previous MI
38 (31.9%)
29 (24.4%)
0.20
Previous PCI
44 (37.0%)
39 (32.8%)
0.50
9 (7.6%)
15 (12.6%)
0.20
Chronic renal failure
Previous CABG
Baseline Characteristics (II)
Rota + PES
n = 120
PTCA + PES
n = 120
P
Value
17 (14.3%)
16 (13.4%)
0.85
11 (9.2%)
8 (6.7%)
0.47
Multivessel disease
88 (74.0%)
88 (74.0%)
1.0
LV ejection fraction (%)
55.5±10.6
53.0±11.5
0.10
11 (9.3%)
9 (7.6%)
0.64
Multilesion PCI
23 (19.3%)
32 (27.1%)
0.16
Unfractionated heparin
49 (41.2%)
70 (50.4%)
0.15
Bivalirudin
70 (58.8%)
59 (49.6%)
0.15
4 (3.4%)
0
0.12
Unstable angina
Left main disease
Ad-hoc PCI
GP IIb/IIIa antagonists
Angiographic Characteristics
Rota + PES
n = 146
PTCA + PES
n = 176
Location
Left main (protected)
P
Value
0.06
3 (2.1%)
2 (1.1%)
101 (69.2%)
111 (63.1%)
7 (4.8%)
22 (12.5%)
35 (24.0%)
41 (23.3%)
Reference vessel diameter (mm)
3.1±0.4
3.1±0.3
0.54
Lesion length (mm)
20.6±9.3
18.5±9.2
0.04
Diameter stenosis %)
81.5±10.2
80.0±10.8
0.23
Ostial location
27 (18.5%)
31 (17.6%)
0.84
Bifurcation
72 (49.3%)
82 (46.6%)
0.63
Moderate/severe tortuosity
67 (46.2%)
83 (47.2%)
0.82
Severe calcification
65 (44.5%)
86 (49.1%)
0.38
B2/C lesion
137 (93.8%)
152 (86.3%)
0.03
Left anterior descending
Left circumflex
Right coronary artery
Procedural Characteristics
Rota + PES
n = 146
PTCA + PES
n = 176
P
Value
7 Fr guiding catheter
122 (83.6%)
50 (28.4%)
<0.001
Balloon predilatation
130 (89.0%)
160 (90.9%)
0.58
Max. predil. balloon size (mm)
2.5±0.3
2.6±0.4
0.37
Max. predil. balloon pressure (atm)
13.6±5.1
15.8±4.9
0.04
Starting burr size (mm)
1.5±0.2
--
--
Max. burr size (mm)
1.5±0.2
--
--
Use of > 1 burr
8 (5.5%)
--
--
165,947±8,919
--
--
1.3±0.6
1.3±0.6
0.25
Total stent length / lesion (mm)
27.7±12.2
25.2±11.5
0.06
Balloon postdilatation
92 (63.0%)
116 (65.9%)
0.86
Max. postdil. balloon size (mm)
3.3±0.5
3.3±0.4
0.88
Max. postdil. balloon pressure (atm)
21.7±5.8
21.5±5.8
0.76
Rotational speed (RPM)
No. of stents / lesion
Procedural Outcome (I)
Rota + PES
n = 120
PTCA + PES
n = 120
P
Value
Procedural duration (min)
66.4±44.5
57.4±34.5
0.05
Fluoroscorpy time (min)
22.8±21.9
18.1±16.7
0.04
201.0±113.6
181.8±93.6
0.11
Dissections
4 (3.3%)
4 (3.3%)
1.0
Perforations
2 (1.7%)
1 (0.8%)
0.56
No/slow flow
0
1 (0.8%)
0.32
Contrast amount (ml)
Procedural Outcome (II)
p = 1.0
100%
96.7%
Rota+PES
PTCA+PES
96.7%
p = 0.03
92.5%
83.3%
80%
60%
40%
p = 0.02
p = 0.08
20%
0
0%
Angiographic
success*
2.5%
Stent loss
12.3%
4.2%
Crossover
* Defined as <20% residual stenosis + TIMI 3 flow
** Defined as angiographic success with no crossover or stent loss
Strategy
success**
In-Hospital Outcome
Rota+PES
PTCA+PES
10%
p = 0.17
8%
5.9%
6%
4.2% 4.2%
3.4%
4%
2%
0%
1.7%
1.7%
1.7%
0.8% 0.8%
0
Death
0.8%
0
MI
* Defined as death, MI and TVR
TV Re-PCI
CABG
0
MACE*
0
ST
Access
site
compl.
QCA data: Index procedure
Rota + PES
n = 123
PTCA + PES
n = 132
P
Value
Lesion length (mm)
19.56±9.64
18.63±9.70
0.44
Refernce vessel diameter (mm)
2.67±0.41
2.77±0.37
0.04
Minimal lumen diameter (mm)
1.01±0.36
1.10±0.39
0.05
62.05±11.92
60.18±12.74
0.17
In-stent
2.58±0.37
2.56±0.40
0.61
In-segment
2.27±0.50
2.27±0.49
0.98
In-stent
10.43±5.25
11.82±5.21
0.03
In-segment
17.68±8.98
19.38±16.67
0.18
In-stent
1.57±0.43
1.46±0.46
0.03
In-segment
1.26±0.54
1.17±0.53
0.18
Before procedure
Diameter stenosis (%)
Immediately after procedure
Minimal lumen diameter (mm)
Diameter stenosis (%)
Acute gain (mm)
Primary Endpoint
In-Stent Late Lumen Loss at 9 Months
Rota+PES
PTCA+PES
0,5
0.44 mm
0,4
0.31 mm
0,3
0,2
0,1
0,0
Primary Endpoint
In-Stent Late Lumen Loss at 9 Months
Rota+PES
PTCA+PES
0,5
p = 0.01
0.44 mm
0,4
0.31 mm
0,3
0,2
0,1
0,0
QCA data: 9-month reangiography
Rota + PES
n = 123
PTCA + PES
n = 132
P
Value
In-stent
2.14±0.63
2.25±0.62
0.15
In-segment
1.91±0.57
2.02±0.65
0.16
In-stent
22.01±19.92
19.86±19.64
0.26
In-segment
27.92±18.97
26.99±1.73
0.44
In-stent
0.44±0.58
0.31±0.52
0.01
In-segment
0.36±0.57
0.25±0.57
0.04
In-stent
14 (11.4%)
14 (10.6%)
0.84
In-segment
15 (12.2%)
17 (12.9%)
0.87
Minimal lumen diameter (mm)
Diameter stenosis (%)
Late lumen loss (mm)
Binary restenosis (%)
Events at Follow-Up
Rota+PES
PTCA+PES
50%
40%
p = 0.46
30%
p = 0.73
20%
18.3%
16.7%
p = 0.78
10%
5.0% 5.8%
p = 0.79
28.3%
24.2%
p = 0.84
11.7%12.5%
p = 1.0
6.7% 5.8%
0.8%
0%
Death
* Defined as death, MI and TVR
MI
TVR
TLR
MACE*
0
Definite ST
Summary (I)
• Rotablation + PES implantation was not superior
to balloon dilatation + PES implantation in
reducing the primary endpoint of late lumen loss
at 9 months in patients with complex calcified
coronary artery disease.
• Rotablation (probably due to additional vessel
trauma) rather decreased the efficacy of PES in
reducing neointimal growth.
Summary (II)
• The superior acute gain obtained by rotablation
was counterbalanced by an increased late loss
resulting in a neutral effect on restenosis.
• Rotablation remains an important bail-out device
for uncrossable or undilatable coronary lesions
and can improve overall success of DES
implantation.
Thank You
ROTAXUS
Heart Center, Bad Segeberg, Germany