Transcript The NOTION Trial Lars Søndergaard The Heart Center, Rigshospitalet, Copenhagen, Denmark - on behalf of the NOTION Investigators.

The NOTION Trial
Lars Søndergaard
The Heart Center, Rigshospitalet, Copenhagen, Denmark
- on behalf of the NOTION Investigators
Funding
• The Danish Heart Foundation
Nordic Aortic Valve Intervention
(NOTION) Trial
Objective:
Primary
outcome:
Secondary
outcomes:
Design:
Enrollment
period:
Compare TAVI vs. SAVR in patients >70 years
eligible for surgery (all-comers population)
Composite rate of death from any cause,
stroke or myocardial infarction at 1 year
(VARC II-defined)
Safety and efficacy (NYHA),
echocardiographic outcomes
(VARC II-defined)
Prospective, multicenter, non-blinded,
randomized trial
December 2009 - April 2013
Participating Centers
Sahlgrenska
University
Hospital,
Gothenburg,
Sweden
Rigshospitale
t
Copenhagen
Denmark
Odense University Hospital
Denmark
Trial Investigators and CEC
Principal Investigators:
Peter Bo Hansen
Lars Søndergaard
Lars Willy Andersen
Daniel Andreas Steinbrüchel
Henrik Nissen
Bo Juel Kjeldsen
Co-investigators:
Petur Petursson
Hans Gustav Hørsted Thyregod
Peter Skov Olsen
Clinical Events Committee:
Nikolaj Ihlemann
Kristian Thygesen, cardiologist
Olaf Walter Franzen
Bo Norrving, neurologist
Thomas Engstrøm
Torben Schroeder, vascular surgeon
Peter Clemmensen
Enrollment Criteria
Main inclusion criteria
Main exclusion criteria
•Severe AS
• Severe CAD
•Age ≥70 years
• Severe other valve disease
•Life expectancy ≥ 1 year
• Prior heart surgery
•Suitable for TAVR & SAVR
• Need for acute treatment
• Recent stroke or MI
• Severe lung disease
• Severe renal failure
Device and Access Routes
Subclavian
Self-expanding
Bioprosthesis
(annulus diameter
18-29 mm )
Transfemoral
18Fr delivery system
Sample Size Determination
Alternative hypothesis
TAVI is superior to SAVR regarding the composite rate of
death from any cause, stroke MI after 1 year
Sample size determination
Expected rateSAVR = 15%, Expected rateTAVI = 5%
1:1 treatment allocation, 2-sided alpha = 0.05, Power = 80%
Trial size: 280 patients
Trial Flow
Trial Compliance
ITT TAVI
N=145
ITT SAVR
N=135
Baseline
100%
(145/145)
100%
(135/135)
1 Month Follow-Up
96.4%
(135/140)
92.1%
(116/126)
3 Months Follow-Up
96.4%
(135/140)
93.6%
(117/125)
1 Year Follow-Up
98.5%
(134/136)
96.0%
(119/124)
2 Year Follow-Up
94.6%
(123/130)
95.8%
(113/118)
Baseline Characteristics
Characteristic, % or mean ± SD
Age (yrs)
Male
STS Score
STS Score < 4%
Logistic EuroSCORE I
NYHA class III or IV
TAVI
n=145
SAVR
n=135
79.2 ± 4.9 79.0 ± 4.7
p-value
0.71
53.8
52.6
0.84
2.9 ± 1.6
3.1 ± 1.7
0.30
83.4
80.0
0.46
8.4 ± 4.0
8.9 ± 5.5
0.38
48.6
45.5
0.61
Baseline Characteristics
TAVI
n=145
SAVR
n=135
pvalue
Diabetes
17.9
20.7
0.55
Peripheral Vascular Disease
4.1
6.7
0.35
Prior Stroke
6.2
9.6
0.29
COPD
11.7
11.9
0.97
Creatinine > 2 mg/dl
1.4
0.7
>0.99
Prior Myocardial Infarction
5.5
4.4
0.68
Prior PCI
7.6
8.9
0.69
Characteristic, % or mean ± SD
Primary Outcome*
Composite rate of
death from any cause, stroke or myocardial infarction
1 year after the procedure
TAVI 13.1% vs. SAVR 16.3%
Absolute difference -3.2%; p=0.43 (for superiority)
*Intention-to-treat population
Death from Any Cause, Stroke, or MI
P-Value
P-Value (log-rank)
(log-rank) == 0.4252
0.43
Death from Any Cause at 2 Years
P-value (log-rank) = 0.54
Secondary Outcomes at 2 Years
1 Year
2 Years
Outcome, %
TAVI
SAVR
p-value
TAVI
SAVR
p-value
Death, any cause
4.9
7.5
0.38
8.0
9.8
0.54
Death, cardiovascular
4.3
7.5
0.25
6.5
9.1
0.40
Stroke
2.9
4.6
0.44
3.6
5.4
0.46
TIA
2.1
1.6
0.71
6.0
3.3
0.30
Myocardial infarction
3.5
6.0
0.33
5.1
6.0
0.69
Atrial fibrillation
21.2
59.4
<0.001
22.7
60.2
<0.001
Pacemaker
38.0
2.4
<0.001
41.3
4.2
<0.001
Aortic valve re-intervention
0.0
0.0
na
0.0
0.0
na
Aortic Valve Performance
Aortic Valve Regurgitation
NYHA Class in Survivors
Conclusions (I)
• The NOTION trial was the first all-comers
trial to randomize lower-risk patients to
TAVI or SAVR
• TAVI was safe and effective, and
comparable to SAVR regarding the
composite rate of death from any cause,
stroke or myocardial infarction after 2
years
Conclusions (II)
• TAVI resulted in larger EOA and lower
gradients, but higher rate of moderate
aortic regurgitation than SAVR
• These two year data support the safety
and effectiveness of TAVI in lower risk
patients
• Longer term data on durability and more
randomized clinical trials in lower risk
patients are necessary