Transcript A Prospective, Randomized Trial of Transapical Transcatheter Aortic Valve Implantation vs. Surgical Aortic Valve Replacement in Operable Elderly Patients with Aortic Stenosis The STACCATO Trial Hans.

A Prospective, Randomized Trial of
Transapical Transcatheter Aortic
Valve Implantation vs. Surgical Aortic Valve
Replacement in Operable Elderly Patients
with Aortic Stenosis
The STACCATO Trial
Hans H. M. Nielsen, Kaj E. Klaaborg, Henrik Nissen, Kim
Terp, Poul E. Mortensen, Bo J. Kjeldsen, Carl-Johan
Jakobsen, Henning R. Andersen, Lars R. Krusell, Henrik
Egeblad, Evald H. Christiansen, Jacob R. Greissen, Erik
Sloth, Leif Thuesen, Vibeke E. Hjortdal
A Prospective, Randomized Trial of Transapical
Transcatheter Aortic
Valve Implantation vs. Surgical Aortic Valve
Replacement in Operable Elderly Patients with
Aortic Stenosis
The STACCATO Trial
Conflicts of interests for Leif Thuesen, M.D.
Edwards Lifesciences:
Physician proctor
Background
Transcatheter aortic valve implantation (TAVI)
has become a treatment option for patients with
aortic valve stenosis, who are not amenable or
at high risk to surgical valve replacement
(SAVR)
The role of TAVI in surgically lower risk patients
remains to be defined
Purpose
In a prospective, randomized trial to compare
transapical transcatheter aortic valve
implantation (a-TAVI) with surgical aortic valve
replacement (SAVR) in operable elderly
patients
Funding
Academic study funded by the participating
centers
We received a study grant from the Danish Heart
Foundation
The study was conducted without relationship to
the industry
Material and methods
Planned number of patients
n= 200
Randomization
1:1
Participating centers
Departments of Cardiothoracic Surgery and
Cardiology, Aarhus University Hospital and
Odense University Hospital, Denmark
Criteria of inclusion
•
•
•
•
Valvular aortic stenosis (valve area <1cm2)
Age ≥70 or 75 yrs
Condition accessible both by SAVR and a-TAVI
Expected survival >1 year following successful
treatment
Criteria of exclusion
• Coronary artery disease to be treated by PCI or
CABG
• Previous myocardial infarction or cardiac surgery
or PCI within 12 months
• Need for emergency surgery
• Unstable cardiac condition (assist device or
inotropes)
• Stroke within 1 month
• Reduced pulmonary function
• Renal failure to be treated by hemodialysis
Primary endpoint
• The composite of 30-day all cause
mortality, major stroke, and/or renal failure
Secondary endpoints
•
•
•
•
•
Myocardial infarction
Operation for bleeding
Permanent pacemaker treatment
Duration of hospital stay
Echocardiographic parameters (aortic
valve area, peak aortic valve gradient,
aortic valve leakage, left ventricular
ejection fraction)
• NYHA class, SF-36 composite physical
and mental functional scores
Definitions
For endpoint definitions, we used the Valve
Academic Research Consortium
recommendations
Sample size
We anticipated a primary endpoint rate of 13.5% in
the SAVR group based on Western Denmark Heart
Registry SAVR data on patients aged ≥70 yrs from
1998 through 2008.
The estimated event rate of 2.5% in the a-TAVI
group was based on our experience from nonoperable patients with significantly higher risk than
the study population. At study initiation, our a-TAVI
event rates were 0%.
Given an alpha of 5% and a beta of 80%, 96 patients
should be included in each group to document the
difference. Therefore, we planned for inclusion of
200 patients.
Premature termination
After inclusion of 70 patients, the study was
terminated prematurely after advice from the Data
Safety Monitoring Board
Conduct of the study
• June 2008; protocol
─
Scenario; a-TAVI safe, predictable procedure
• September 2008; MEC approval
• November 2008; 1. patient included
• Study on hold after inclusion of 11 patients
─
3 potentially severe adverse events in the a-TAVI group
─
Contact with DSMB and MEC
─
Inclusion and exclusion criteria modified (age limit increased to
75 yrs, earlier heart operation reason for exclusion)
─
Inclusion resumed
• Study on hold May 2011
─
DSMB advised study termination due to an excess of events in
the a-TAVI group
Patient flow-diagram
Assessed for eligibility
(n= 525)
Randomized (n= 72)
Excluded after randomization (n= 2)
a-TAVI
(n=34)
SAVR
(n=36)
Excluded (n = 453)
• Medical Tx (n=24)
• Surgical Tx (n=285)
• TAVI (n= 144)
Baseline characteristics
Characteristics
a-TAVI
SAVR
p Value
Age (yrs)
80±3.6
82±4.4
0.15
Male sex
9/34 (26.5)
12/36 (33.3)
0.61
Diabetes
1/34 (2.9)
3/36 (8.3)
0.62
Cerebral vascular disease
1/34 (2.9)
1/36 (2.8)
1.00
Peripheral vascular disease
2/34 (5.9)
3/36 (8.3)
1.00
COPD
1/34 (2.9)
1/36 (2.8)
1.00
Creatinine level >200µmol/L
1/34 (2.9)
0/36 (0.0)
0.49
Logistic EuroSCORE
9.4±3.9
10.3±5.8
0.25
STS score
3.1±1.5
3.4±1.2
0.43
18/34 (58.1)
16/36 (44.4)
0.63
EF (%)
56.5±9.7
56.3±10
0.92
Aortic valve area (cm2)
0.66±0.17
0.71±0.17
0.21
NYHA class III or IV
Primary endpoint events
Allocation Sex, age
Adverse event
Time for event
Outcome
a-TAVI
♀, 80
Death
On waiting list
Not treatment related
a-TAVI
♀, 70
Left coronary artery blockage
Perioperative
Acute CABG/SAVR, death day 1
a-TAVI
♀, 79
Major stroke
Day 27
Severe disability, death day 34
a-TAVI
♀, 86
Major stroke
Day 16
Severe disability
a-TAVI
♀, 76
Renal failure requiring dialysis
Day 8
Hemodialysis
SAVR
♀,81
Major stroke
Perioperative
Severe disability
p=0.07
Other events at 3 months
Allocation Sex, age
Adverse event
Time for event
Outcome
Perioperative
Partial recovery
Perioperative
SAVR, recovery
Perioperative
a-TAVI
♀, 81
a-TAVI
♂, 80
a-TAVI
♀, 79
Transient ischemic attack with
later major stroke
Left main occlusion during
balloon valvuloplasty
Aortic rupture
a-TAVI
♂, 75
Severe paravalvular leakage
Perioperative
Emergency implantation of
homograft, recovery
SAVR, recovery
a-TAVI
♀, 82
Severe paravalvular leakage
Perioperative
SAVR, death day 38
a-TAV
♂, 78
THV embolization upstream
Perioperative
a-TAVI
♀, 80
Abnormally positioned heart
Perioperative
Implantation of another THV,
recovery
SAVR, recovery
a-TAVI
♀, 86
Bleeding
Postoperative
Re-operation, recovery
SAVR
♀,83
Perioperative
a-TAVI, recovery
SAVR
♂,82
Conversion to a-TAVI because of
intrathoracic goiter
Bleeding
Postoperative
Re-operation, recovery
cm2
Aortic valve area
Baseline and after treatment
p=0.15
p=0.15
‡
‡
‡ p<0.0001 as compared to pretreatment values
Peak aortic gradient
mmHg Baseline and after treatment
p=0.07
‡
‡
‡ p<0.0001 as compared to pretreatment values
Paravalvular leakage
after treatment
n=4
(13%)
n=2
(6%)
n=13
(43%)
n=33
(94%)
n=13
(43%)
p<0.001
n
NYHA class
Baseline and at 3 months
p=0.16
p=0.01
p=0.001
Other outcome parameters
Parameters
a-TAVI
SAVR
p Value
Myocardial infarction *
n/N (%)
Permanent pacemaker
n/N (%)
Hospital stay
(days)
Composite physical functional score
before treatment (%)
0/0 (0)
0/0 (0)
1.00
2/34 (5.8)
1/36 (2.7)
0.52
8.8±6.7
7.6±2.4
0.32
35±10, n=27
37±12, n=32
0.48
Composite physical functional score
3 months after treatment (%)
42±14, n=27‡
43±15, n=32‡
0.91
Composite mental functional score
before treatment (%)
Composite mental functional score 3
months after treatment (%)
47±10, n=27
46±17, n=32
0.66
53±14, n=27‡
50±17, n=32‡
0.44
* Valve Academic Research Consortium definition
‡ ns; as compared to pretreatment values
Limitations
• Premature study termination; only one third of
the anticipated number of patients included
• The excess of adverse events in the a-TAVI
group might be a play of chance
• Only two centers were actively including. The
SAVR results were excellent, but a-TAVI results
might have been different with participation of
more centers
• Multi-slice computed tomography (MSCT) was
not used in the preoperative assessment
Issues for discussion
• Stroke
~
Perioperative; 1 major stroke in the SAVR group, 1 TIA in the
a-TAVI group
~
Two major strokes after 2-4 weeks in the a-TAVI group during
dual antiplatelet treatment
• Paravalvular leakage
~
Absent in the SAVR group
~
Moderate to severe leakage in 13% of a-TAVI patients,
probably because of valve under sizing. Preoperative MSCT
might have optimized valve sizing
• Perioperative coronary artery occlusion
~
Might have been avoided by preoperative MSCT assessment
of annulus to left main distance and valve/left main relation
Conclusion
• In its present phase of development, transapical
transcatheter aortic valve implantation seems
inferior to surgical aortic valve replacement in
operable elderly patients
Final remarks
• After study termination, our procedures have
been optimized by routine preoperative MSCT
assessment and by availability of the 29 mm
valve
• Further improvement is likely to take place with
improved devices and pre-procedure assessment