Updates From NOTION:
The First All-Comer TAVR Trial
Lars Sondergaard, MD, DMSc
Professor of Cardiology
Rigshospitalet
Copenhagen, Denmark
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
BSci, SJM, Symetis
BSci, Medtronic, SJM, Symetis
Nordic Aortic Valve Intervention Trial The
NOTION Trial
Objective:
Compare TAVR vs. SAVR in patients >70 years
eligible for surgery (all-comers population)
Composite rate of death from any cause, stroke or
Primary outcome:
myocardial infarction at 1 year (VARC II-defined)
Secondary
outcomes:
Safety and efficacy (NYHA), echocardiographic
outcomes (VARC II-defined)
Design:
Prospective, multicenter, non-blinded, randomized
trial
Enrollment
period:
December 2009 - April 2013
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
Self-expanding
Bioprosthesis
(annulus diameter
18-29 mm )
Transfemoral
18Fr delivery system
Subclavian
Baseline Characteristics
Characteristic, % or mean ± SD
Age (yrs)
Male
STS Score
STS Score < 4%
Logistic EuroSCORE I
NYHA class III or IV
TAVR
n=145
SAVR
n=135
pvalue
79.2 ±
4.9
79.0 ± 4.7
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
Trial Compliance
ITT TAVR
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)
Primary Outcome*
Composite rate of
death from any cause, stroke or myocardial infarction
1 year after the procedure
TAVR 13.1% vs. SAVR 16.3%
Absolute difference -3.2%; p=0.43 (for superiority)
*Intention-to-treat population
All-cause mortality, stroke or MI
Sondergaard et al. Circ carciovasc Interv 2016
All-cause mortality, Stroke or MI
Patients with STS <4%
Sondergaard et al. Circ carciovasc Interv 2016
Functional Class
Baseline
3 months
1 year
2 years
Sondergaard et al. Circ carciovasc Interv 2016
Valve Performance
Δ EOA
Δ Mean gradient
Sondergaard et al. Circ carciovasc Interv 2016
Aortic Valve Regurgitation
3 months
1 year
2 years
Sondergaard et al. Circ carciovasc Interv 2016
All-cause mortality in TAVR patients
according to PVL rate
Sondergaard et al. Circ carciovasc Interv 2016
Conclusions (I)
• The NOTION trial was the first all-comers trial to
randomize lower-risk patients to TAVR or SAVR
• TAVR 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)
• TAVR resulted in larger EOA and lower gradients,
but higher rate of moderate PVL than SAVR
• These two year data support the safety and
effectiveness of TAVR in lower risk patients
• Longer term data on durability and more
randomized clinical trials in lower risk patients
are necessary
All-cause mortality benefits for TAVI
ALL-CAUSE MORTALITY AT 2 YEARS
4 RANDOMIZED TRIALS (N =3,806)
Trial
TAVR
SAVR
HR (95% CI)
PARTNER 1A
116/348 114/351
0.90 (0.71-1.15)
US CoreValve
85/391
99/359
0.79 (0.61-1.01)
NOTION
11/145
14/135
0.72 (0.33-1.59)
PARTNER 2A
Overall
166/1011 170/1021
0.92 (0.74-1.13)
0.87 (0.76-0.99), P=0.038
Siontis et al. EHJ 2016, in press
RCT in TAVI
12
STS score (%)
10
8
6
4
2
0
Extreme
High
Intermediate Low
RCT in TAVI – same age!
High
Intermediate Low
10
100
8
80
6
60
4
40
2
20
0
0
Age (years)
STS score (%)
12
Extreme
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(n=735)!
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surgical
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Eastern Denmark
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(n=518)!
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68 years
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aortic valves
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(n=735)!
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Cardiovasc
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61 years
(n=735)!
(n=735)!!
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De Backer et al. JACC
Interv 2016
NOTION I – Mortality at 2 Years
NOTION II
Study design
Inclusion criteria
• Severe symptomatic aortic stenosis
• Age ≤75 years & STS score ≤4%
• Anticipated usage of aortic bioprosthesis
Primary end-point
• Composite rate of all-cause mortality, stroke & MI at 1 year
Design
• RCT, 1:1, TF TAVI vs. SAVR, superior, N=992
• Bicuspid valves & revascularization (CABG or PCI) allowed
• Any aortic bioprosthesis allowed