View
0
Download
0
Category
Preview:
Citation preview
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
1:1
1:1
NSTEACS or STEMI with invasive management Aspirin+P2Y12 blocker
Trans-Femoral Access
Heparin
±GPI
Bivalirudin
Mono-Tx
Stop
Infusion Prolong≥ 6 hs
infusion
1:1
Trans-Radial Access
MATRIX Access
Q: Is TRI superior to TFI ?
MATRIX Program registered at
ClinicalTrials.gov, number NCT01433627
Am Heart J. 2014 Dec;168(6):838-45.e6.
Study Organization and Sites
Sponsor
Clinical Event Committee
P. Vranckx, Chair
S. Leonardi Co-Chair
P. Tricoci
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
Statistical Committee (CTU)
P.Jüni, MD, Chair
M. Rothenbühler
Dik Heg
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
Data Mng
E. Frigoli, Eustrategy
Project Leader
Executive Committee
Steering Committee
Committee Members
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.
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
39 93 132 200 276 380 490 685 857 1002 1190
1400 1684 1972 2248
2584 2926
3256 3560
3875 4144
4452 4726
5000 5322
5655 5896 6184
6458 6742 6982 7235 7444 7638 7844 8073
8404
Cumulative enrollment by month
8,404
8,404
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
Complete follow-up to 30 days available in 4183 (99.7%) of radial and 4191 (99·6%) of femoral cohorts
Am Heart J. 2014 Dec;168(6):838-45.e6.
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
Radial (N=4,197) Femoral (N=4,207)
Age (years) 67±12 67±12
Age ≥ 75 ys (%) 28.3 29.3
Male (%) 74.5 72.4
BMI (kg/m2) 27.1±4.1 27.1±4.1
Previous CVA (%) 4.6 5.5
PAD (%) 8.1 8.8
Renal failure (%) 1.1 1.4
Previous PCI (%) 13.9 14.7
Previous radial access (%) 2.8 2.0
Killip > 1 (%) 9.6 9.7
STEMI (%) 47.7 47.8
NSTEMI (%) 46.5 45.9
UA (%) 5.8 6.4
Enoxaparin (%) 16.3 17.5
Fondaparinux (%) 10.2 11.1
UFH (%) 29.5 29.4
Baseline Characteristics
Procedural Characteristics Radial (N=4,197) Femoral (N=4,207)
PCI attempted (%) 80.3 79.8
CABG (%) 3.7 3.7
Medical Tx (%) 11.7 11.9
Medications in the Lab
Clopidogrel (%) 6.4 6.0
Ticagrelor/prasugrel (%) 17.1 16.3
GP IIb/IIIa inhibitors (%) 13.7 12.4
UFH (%) 49.9 45.5
Bivalirudin (%) 40.1 40.7
IABP (%) 1.9 2.3
Treated vessel(%)
LMCA 4.6 3.5
LAD 50.3 49.2
Multivessel PCI (%) 13.7 13.7
Stent lenght (mm) 31.8 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=0.77 P<0.001
*
*: TIMI <3 and/or % final stenosis >30%
%
8.8%
10.3%
15% significant reduction at nominal 5% alpha
which is however NOT significant at the pre-specificed
alpha of 2.5%
Primary EP: MACE
Femoral
Radial
Rate Ratio 0.83; 95% CI, 0.73 to 0.96; p=0.0092
11.7%
9.8%
NNTB: 53 Femoral
Radial
Primary EP: NACE
MI and CVA endpoints: Any MI, STEMI, NSTEMI, unclassified*, stroke, TIA
P=1.00
P=0.059
P=0.20
*: LBBB, paced rhythm or unavailability of interpretable ECG
% %
Fatal and ST EPs: All-Cause, Cardiac, non-CV mortality, type of stent thrombosis
%
RR:0.72
(0.53-0.99)
P=0.045
RR: 0.75
(0.54-1.04)
P=0.08
P=0.69
P=0.66 %
Mortality Stent Thrombosis
NNTB: 167
Bleeding endpoints: BARC, TIMI, GUSTO, access vs non-access related
1.4%
2.5%
%
P=0.013
RR: 0.67 0.49-0.92
P=0.0004
RR: 0.37 0.21-0.66
BARC 3 or 5
P=0.0098
RR: 0.64 0.45-0.90
P=0.08
RR: 0.72 0.50-1.04 P=0.20
RR: 0.78 0.53-1.14
Major
or minor
moderate
or severe
P=0.82
P=0.68
Rardial Better Femoral Better 1
HAZARD RATIO (95% CI)
P-VALUES
Superiority Interaction
0.89 Intermediate (548-991)
0.75 (0.60-0.94)
1.04 (0.82-1.32) 0.76 0.011
Centre’s annual
volume of PCI
Low (247-544)
Intermediate (65.4-79.0%)
Centre’s
Proportion of
radial PCI
Low (14.9-64.4%)
NSTE-ACS (tp–) ACS type
STEMI
<75 Age
≥75 0.23 0.88 (0.70-1.09)
0.82 (0.68-0.97) 0.023 0.62
NACE: Subgroup Analysis
High (1000-1950)
High (80.0-98.0%)
NSTE-ACS (tp+)
Men Sex
Women
<25 BMI
≥25
No
Ticagrelor or
prasugrel Yes
No Diabetes
Yes
<60 GFR
≥60
No
History of
PVD Yes
2 0.25 0.50
0.75 (0.58-0.97) 0.025
0.0048
1.01 (0.79-1.29)
0.95 (0.75 -1.22) 0.71
0.95
0.64 (0.51-0.80) <0.001
0.44
0.86 (0.68-1.08)
0.58 (0.33-1.03) 0.059
0.19
0.85 (0.71-1.02) 0.07
0.012 0.72 (0.56-0.93)
0.89 (0.76-1.05) 0.16 0.18
0.09 0.86 (0.73-1.02)
0.79 (0.63-0.99) 0.038 0.53
0.07 0.83 (0.68-1.02)
0.84 (0.70-1.01) 0.06 0.94
0.45 0.91 (0.71-1.17)
0.80 (0.68-0.94) 0.08 0.43
0.01 0.78 (0.65-0.94)
0.86 (0.70-1.07) 0.18 0.51
0.60 0.91 (0.64-1.30)
0.83 (0.71-0.96) 0.012 0.64
No interaction between access and anticoagulant use in a post- hoc analysis of the subgroup of 7,213 patients randomized to bivalirudin or unfractionated heparin for the two co-primary outcomes, all-cause mortality, or BARC 3 or 5 bleeding
Radial Better Femoral Better 1
HAZARD RATIO (95% CI)
P-VALUES
Superiority Interaction
Intermediate (65.4-79.0%)
Centre’s
Proportion
of radial PCI
Low (14.9-64.4%)
NSTE-ACS (tp–) ACS
type
STEMI
Subgroup Analysis
High (80.0-98.0%)
NSTE-ACS (tp+)
2
0.0157
1.28 (0.71-2.32)
0.69 (0.40 -1.19) 0.18
0.41
0.48 (0.28-0.81) 0.006
0.10
0.87 (0.59-1.29) 0.49
0.49 (0.28-0.87) 0.012
Intermediate (65.4-79.0%) Centre’s
Proportion
of radial PCI
Low (14.9-64.4%)
NSTE-ACS (tp–) ACS
type
STEMI
High (80.0-98.0%)
NSTE-ACS (tp+)
0.20
0.90 (0.54-1.50)
0.57 (0.31 -1.03) 0.06
0.68
0.56 (0.32-0.97) 0.035
0.54
0.62 (0.41-0.94)
1.66 (0.28-10.0) 0.58
0.022
0.70 (0.42-1.17) 0.17
Mortality
Bleeding
4 0.50 0.25
1 2 0.50 0.25
Updated Meta-analysis 19,328 ACS patients being randomly allocated to radial or femoral access
Rardial Better Femoral Better 1 4 0.25 0.50 2
Pre-Rival RIVAL Post-RIVAL MATRI
X Combined
Non-CABG
major bleeds
Death,
myocardial
infarction or
stroke
Death
Myocardial
Infarction
Stroke
Pre-Rival RIVAL Post-RIVAL MATRI
X Combined
Pre-Rival RIVAL Post-RIVAL MATRI
X Combined
Pre-Rival RIVAL Post-RIVAL MATRI
X Combined
Pre-Rival RIVAL Post-RIVAL MATRI
X Combined
SUBGROUP Risk Ratio (95%CI) P Value
Heterogenity
P Value I2
0.73 (0.43-1.23) 0.39 (0.23-0.67)
0.58 (0.46-0.72)
0.41 (0.22-0.76)
<0.0001 0% 0.5
1
0.67 (0.48-0.93) 0.86 (0.76-0.98) 0.86 (0.77-0.95)
0.98 (0.76-1.27)
0.0051 0% 0.9
7
0.58 (0.39-0.87) 0.73 (0.53-0.99) 0.72 (0.60-0.88) 0.0011 0% 1.0
0
0.85 (0.39-1.90) 0.91 (0.78-1.06) 0.91 (0.79-1.04)
0.92 (0.65-1.31)
0.1
6 0% 0.8
8
0.68 (0.49-0.92)
0.82 (0.52-1.29)
0.77 (0.46-1.28) 0.86 (0.58-1.29)
0.73 (0.12-4.47)
1.40 (0.45-4.40) 1.00 (0.50-2.00) 1.05 (0.69-1.60)
1.43 (0.72-2.83)
0.8
0 0% 0.7
5
0.26 (0.06-1.23)
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 meta-
analysis, 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
Recommended