Transcript Diapositiva 1 - American College of Cardiology

Results From The Minimizing
Adverse Haemorrhagic Events By
Transradial Access Site And
Systemic Implementation
of Angiox-MATRIX
Access Program
M. Valgimigli, MD, PhD
Erasmus MC
Rotterdam, The Netherlands
on behalf of the MATRIX Group
NCT01433627
I, Marco Valgimigli, have received:
• Institutional research grant from
Medtronic and The Medicines
Company/Terumo (current study)
• honoraria for lectures/advisory board
from Merck, Correvio, Astra Zeneca,
The Medicines Company, St Jude,
Abbott Vascular, Alvimedica and
Terumo.
Background
• Compared with the femoral, the radial artery is more
superficial and has a smaller calibre. This
characteristic makes access site haemostasis more
predictable, but the procedure itself technically
demanding
• Previous studies have come to differing conclusions
with regards to the role of radial access in reducing
adverse outcomes in patients with ACS
• It remains unclear whether avoiding access site bleeding
and vascular complications through routine transradial
intervention improves outcomes in unselected patients
with ACS undergoing invasive management
MATRIX Access
NSTEACS or STEMI with invasive management
Aspirin+P2Y12 blocker
1:1
Trans-Radial
Access
Trans-Femoral
Access
Q: Is TRI superior to TFI ?
1:1
Bivalirudin
Heparin
Mono-Tx
±GPI
1:1
Stop
Infusion
Prolong≥ 6 hs
infusion
MATRIX Program registered at
ClinicalTrials.gov, number NCT01433627
Am Heart J. 2014 Dec;168(6):838-45.e6.
Study Organization and Sites
Sponsor Gruppo Italiano Studi Emodinamica
Grant suppliers: The Medicines Company and Terumo
Principal Investigator: Marco Valgimigli, MD, PhD
Study Director: Maria Salomone. MD, PhD
78 Sites across 4 EU countries recruited patients
National Coordinating Investigators and CROs
Paolo Calabrò, MD, PhD, Italy; Trial Form Support
Arnoud W J van‘t Hof, MD, The Netherlands; Trial Form Support
Manel Sabate’, MD, PhD, Spain; FLS-Research Support
Elmir Omerovic, MD, PhD, Sweden; Gothia Forum
Clinical Event
Committee
P. Vranckx, Chair
S. Leonardi Co-Chair
P. Tricoci
Statistical
Committee (CTU)
P.Jüni, MD, Chair
M. Rothenbühler
Dik Heg
Data Mng
E. Frigoli, Eustrategy
Project Leader
Committee Members
Executive Committee
Marco Valgimigl, (PI and Chair), Andrea Gagnor; Paolo Calabrò, Paolo
Rubartelli, Stefano Garducci, Giuseppe Andò, Andrea Santarelli, Mario
Galli; Roberto Garbo; Ezio Bramucci; Salvatore Ierna, Carlo Briguori,
Bernardo Cortese; Ugo Limbruno, Roberto Violini; Patrizia Presbitero;
Nicoletta de Cesare; Paolo Sganzerla; Arturo Ausiello; Paolo Tosi;
Gennaro Sardella; Manel Sabate’; Salvatore Brugaletta.
Steering Committee
Giovanni Saccone; Pietro Vandoni, Antonio Zingarelli; Armando Liso;
Stefano Rigattieri, Emilio Di Lorenzo, Carlo Vigna; Cataldo Palmieri;
Camillo Falcone, Raffaele De Caterina, Marcello Caputo; Giovanni
Esposito; Alessandro Lupi; Pietro Mazzarotto, Fernando Varbella; Tiziana
Zaro; Marco Nazzaro; Sunil V. Rao, Arnoud WJ van‘t Hof; Elmir
Omerovic.
MATRIX Access
8,404 patients with ACS undergoing coronary angiography ± PCI
from 11th Oct 2011 to 7th Nov 2014
Operator Eligibility Criteria: Interventional cardiologist
expertise in TRI and TFI including at least 75 transradial
coronary interventions and at least 50% of interventions
performed via radial route in the year preceding site initiation
8,404
Am Heart J. 2014 Dec;168(6):838-45.e6.
8,404
8404
78448073
7638
72357444
6982
6742
6458
6184
Complete follow-up to 30 days available in 4183
56555896
5322
(99.7%) of radial and 4191 (99·6%) of femoral
5000
4726
4452
4144
cohorts
3875
3560
3256
2926
2584
2248
1972
14001684
1190
685 857 1002
490
276 380
39 93 132 200
Cumulative enrollment by month
Patient Eligibility
UA/NSTEMI
New or worsening ischaemia,
occurring at rest or with
minimal activity within 7 days
AND
At least 2 high-risk criteria:
Age > 60
High Tp T I or CK-MB
ECG changes
suggesting ischemia
STEMI
Chest pain for >20 min with
ST-segment elevation ≥1 mm
in two or more contiguous
leads, or with a new left LBBB
or true posterior myocardial
infarction
AND
Admission <12 hs
OR
Between 12 and 24 hs with
evidence of continuing
ischemia or lysis
Of note: Cardiogenic shock, severe PVD and prior CABG were eligible
Endpoints
The MATRIX Access program had two pre-specified
primary superiority endpoints at 30 days:
MACE: composite of death, MI and stroke
NACE: composite of death, MI or stroke and
major bleeding (BARC 3 or 5)
For both the RR was assumed in the range of 0.70 with a background event rate of
6% and 9%, respectively. With an alpha error set at 2.5%, 3,400 patients per group
would provide study power greater than 90% and 99% for MACE and NACE,
respectively.
Major 2 EPs: each component of the co-primary
endpoints, any bleeding according to BARC, TIMI and
GUSTO scales and stent thrombosis
Baseline Characteristics
Radial (N=4,197)
Age (years)
Age ≥ 75 ys (%)
Male (%)
BMI (kg/m2)
Previous CVA (%)
PAD (%)
Renal failure (%)
Previous PCI (%)
Previous radial access (%)
Killip > 1 (%)
STEMI (%)
NSTEMI (%)
UA (%)
Enoxaparin (%)
Fondaparinux (%)
UFH (%)
67±12
28.3
74.5
27.1±4.1
4.6
8.1
1.1
13.9
2.8
9.6
47.7
46.5
5.8
16.3
10.2
29.5
Femoral (N=4,207)
67±12
29.3
72.4
27.1±4.1
5.5
8.8
1.4
14.7
2.0
9.7
47.8
45.9
6.4
17.5
11.1
29.4
Procedural Characteristics
Radial (N=4,197)
PCI attempted (%)
CABG (%)
Medical Tx (%)
Medications in the Lab
Clopidogrel (%)
Ticagrelor/prasugrel (%)
GP IIb/IIIa inhibitors (%)
UFH (%)
Bivalirudin (%)
IABP (%)
Treated vessel(%)
LMCA
LAD
Multivessel PCI (%)
Stent lenght (mm)
Femoral (N=4,207)
80.3
3.7
11.7
79.8
3.7
11.9
6.4
17.1
13.7
49.9
40.1
1.9
6.0
16.3
12.4
45.5
40.7
2.3
4.6
50.3
13.7
31.8
3.5
49.2
13.7
31.4
Cross Over and Procedural
Success Rates
94.1% of radial and 97.4% of
femoral cohorts received
respective treatment as allocated
In 5.8% of radial and 2.3% of TF
cohort the allocated access was
attempted but failed.
In 3 (0.1%) in the radial and 13
(0.3%) patients in the femoral
groups the allocated access was
not attempted
%
P<0.001
P=0.77
*
*: TIMI <3 and/or % final stenosis >30%
Primary EP: MACE
10.3%
8.8%
15% significant reduction at nominal 5% alpha
which is however NOT significant at the pre-specificed
alpha of 2.5%
Femoral
Radial
Primary EP: NACE
11.7%
9.8%
Rate Ratio 0.83; 95% CI, 0.73 to 0.96; p=0.0092
NNTB: 53
Femoral
Radial
MI and CVA endpoints:
Any MI, STEMI, NSTEMI, unclassified*, stroke, TIA
*: LBBB, paced rhythm or unavailability of interpretable ECG
%
P=0.20
%
P=1.00
P=0.059
Fatal and ST EPs:
All-Cause, Cardiac, non-CV mortality, type of stent thrombosis
Mortality
RR:0.72
RR: 0.75
(0.53-0.99)
(0.54-1.04)
P=0.045
%
P=0.08
NNTB: 167
Stent Thrombosis
P=0.66
%
P=0.69
Bleeding endpoints:
BARC, TIMI, GUSTO, access vs non-access related
P=0.0098
RR: 0.64
%
0.45-0.90
P=0.08
RR: 0.72
0.50-1.04
P=0.0004
RR: 0.37
0.21-0.66
P=0.20
RR:
0.78
2.5%
0.53-1.14
P=0.68
P=0.013
RR: 0.67
1.4%
0.49-0.92
P=0.82
BARC 3 or 5
Major
or minor
moderate
or severe
NACE: Subgroup Analysis
P-VALUES
HAZARD RATIO (95% CI) Superiority
Interaction
Low (247-544)
Centre’s annual
Intermediate (548-991)
volume of PCI
High (1000-1950)
0.75 (0.60-0.94)
1.04 (0.82-1.32)
0.75 (0.58-0.97)
0.011
0.76
0.025
0.89
Centre’s
Proportion of
radial PCI
0.95
0.71
<0.001
0.0048
High (80.0-98.0%)
1.01 (0.79-1.29)
0.95 (0.75 -1.22)
0.64 (0.51-0.80)
ACS type
STEMI
NSTE-ACS (tp–)
0.86 (0.68-1.08)
0.58 (0.33-1.03)
0.85 (0.71-1.02)
0.19
0.059
0.07
0.44
0.88 (0.70-1.09)
0.23
0.023
0.62
Low (14.9-64.4%)
Intermediate (65.4-79.0%)
NSTE-ACS (tp+)
≥75
<75
Age
0.82 (0.68-0.97)
No
Sex
0.72
(0.56-0.93)
Womenbetween access and anticoagulant
interaction
use
in a post- 0.012
0.18
0.16
0.89 (0.76-1.05)
Men
hoc analysis of the subgroup of 7,213 patients randomized to bivalirudin
0.09
0.86
(0.73-1.02)
≥25
or unfractionated
heparin for the two co-primary
outcomes,
all-cause
BMI
0.53
0.038
0.79 (0.63-0.99)
<25
mortality, or BARC 3 or 5 bleeding
0.07
0.06
0.94
0.45
0.08
0.43
0.86 (0.70-1.07)
0.01
0.18
0.51
0.91 (0.64-1.30)
0.83 (0.71-0.96)
0.60
0.012
0.64
Ticagrelor or
prasugrel
Yes
No
0.83 (0.68-1.02)
Diabetes
Yes
No
0.91 (0.71-1.17)
GFR
≥60
<60
0.78 (0.65-0.94)
History of
PVD
Yes
No
Rardial Better
0.84 (0.70-1.01)
0.80 (0.68-0.94)
0.25
0.50
1
2
Femoral Better
Subgroup Analysis
P-VALUES
Mortality
Centre’s
Proportion
of radial PCI
ACS
type
HAZARD RATIO (95% CI) Superiority
Low (14.9-64.4%)
1.28 (0.71-2.32)
0.41
Intermediate (65.4-79.0%)
0.69 (0.40 -1.19)
0.18
High (80.0-98.0%)
0.48 (0.28-0.81)
0.006
STEMI
0.87 (0.59-1.29)
0.49
NSTE-ACS (tp–)
Centre’s
Proportion
of radial PCI
ACS
type
0.49 (0.28-0.87)
0.25
0.50
0.012
2
1
Low (14.9-64.4%)
0.90 (0.54-1.50)
0.68
Intermediate (65.4-79.0%)
0.57 (0.31 -1.03)
0.06
0.56 (0.32-0.97)
0.035
STEMI
0.62 (0.41-0.94)
0.022
NSTE-ACS (tp–)
1.66 (0.28-10.0)
0.58
NSTE-ACS (tp+)
0.70 (0.42-1.17)
0.17
High (80.0-98.0%)
0.25 0.50 1
Radial Better
0.0157
0.10
NSTE-ACS (tp+)
Bleeding
Interaction
2
4
Femoral Better
0.20
0.54
Updated Meta-analysis
19,328 ACS patients being randomly allocated to radial or femoral access
Heterogenity
SUBGROUP
Non-CABG
major bleeds
Death,
myocardial
infarction or
stroke
Death
Myocardial
Infarction
Stroke
Risk Ratio (95%CI)
P Value
I2
P Value
Pre-Rival
RIVAL
Post-RIVAL
MATRI
C
X ombined
0.41 (0.22-0.76)
0.73 (0.43-1.23)
0.39 (0.23-0.67)
0.68 (0.49-0.92)
0.58 (0.46-0.72)
<0.0001
0%
0.5
1
Pre-Rival
RIVAL
Post-RIVAL
MATRI
C
X ombined
0.82 (0.52-1.29)
0.98 (0.76-1.27)
0.67 (0.48-0.93)
0.86 (0.76-0.98)
0.86 (0.77-0.95)
0.0051
0%
0.9
7
Pre-Rival
RIVAL
Post-RIVAL
MATRI
Combined
X
0.77 (0.46-1.28)
0.86 (0.58-1.29)
0.58 (0.39-0.87)
0.73 (0.53-0.99)
0.72 (0.60-0.88)
0.0011
0%
1.0
0
Pre-Rival
RIVAL
Post-RIVAL
MATRI
Combined
X
0.73 (0.12-4.47)
0.92 (0.65-1.31)
0.85 (0.39-1.90)
0.91 (0.78-1.06)
0.91 (0.79-1.04)
0%
0.8
8
Pre-Rival
RIVAL
Post-RIVAL
MATRI
Combined
X
0.26 (0.06-1.23)
1.43 (0.72-2.83)
1.40 (0.45-4.40)
1.00 (0.50-2.00)
1.05 (0.69-1.60)
0.1
6
0.8
0
0%
0.7
5
Rardial Better
0.25
0.50
1
2
4
Femoral Better
Summary
• Among patients with an ACS, with or without ST-segment
elevation who underwent invasive management, the use
of radial access for coronary angiography ± PCI reduced
the rate of net adverse clinical events, with a number
needed to treat for benefit of 53
– Differences between groups were driven by reductions in BARC
major bleeding unrelated to CABG and all-cause mortality with
radial access.
• Our results, in conjunction with the updated metaanalysis, suggest that radial approach should
become the default access for patients with ACS
undergoing invasive management
MATRIX Access Program
http://dx.doi.org/10.1016/S0140-6736(15)60507-4