Diapositiva 1

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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
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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.

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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

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MATRIX Access
NSTEACS or STEMI with invasive management Aspirin
P2Y12 blocker
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Trans-Femoral Access
Trans-Radial Access
Q Is TRI superior to TFI ?
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Heparin GPI
Bivalirudin Mono-Tx
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Stop Infusion
Prolong 6 hs infusion
Am Heart J. 2014 Dec168(6)838-45.e6.
MATRIX Program registered at ClinicalTrials.gov,
number NCT01433627
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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 vant 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
Statistical Committee (CTU)
Data Mng
P. Vranckx, Chair S. Leonardi Co-Chair P. Tricoci
P.Jüni, MD, Chair M. Rothenbühler Dik Heg
E. Frigoli, Eustrategy Project Leader
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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
vant Hof Elmir Omerovic.
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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 Dec168(6)838-45.e6.
8,404
Cumulative enrollment by month
Complete follow-up to 30 days available in 4183
(99.7) of radial and 4191 (996) of femoral
cohorts
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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 gt
60 High Tp T I or CK-MB ECG changes suggesting
ischemia
STEMI Chest pain for gt20 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 lt12
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
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Key Exclusion Criteria

• LMWH in the previous 6 h
• Glycoprotein IIb/IIIa inhibitors in the previous
  3 days
• Any PCI performed in the previous 30 days

Of note Cardiogenic shock, severe PVD and prior
CABG were eligible
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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
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Baseline Characteristics

• Radial (N4,197) Femoral (N4,207)
• Age (years) 6712
  6712
• Age 75 ys () 28.3 29.3
• Male () 74.5
  72.4
• BMI (kg/m2) 27.14.1
  27.14.1
• 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 gt 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

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Procedural Characteristics

• Radial (N4,197) Femoral (N4,207)
• 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

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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

P0.77
Plt0.001


TIMI lt3 and/or final stenosis gt30
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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
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Primary EP NACE
11.7
9.8
Rate Ratio 0.83 95 CI, 0.73 to 0.96 p0.0092
Femoral
NNTB 53
Radial
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MI and CVA endpoints Any MI, STEMI, NSTEMI,
unclassified, stroke, TIA
LBBB, paced rhythm or unavailability of
interpretable ECG
P1.00
P0.20


P0.059
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Fatal and ST EPs All-Cause, Cardiac, non-CV
mortality, type of stent thrombosis
Mortality
Stent Thrombosis
P0.66
RR0.72 (0.53-0.99) P0.045

RR 0.75 (0.54-1.04) P0.08
P0.69

NNTB 167
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Bleeding endpoints BARC, TIMI, GUSTO, access vs
non-access related
P0.0098 RR 0.64 0.45-0.90

P0.08 RR 0.72 0.50-1.04
P0.20 RR 0.78 0.53-1.14
2.5
P0.0004 RR 0.37 0.21-0.66
P0.68
P0.013 RR 0.67 0.49-0.92
1.4
P0.82
BARC 3 or 5
Major or minor
moderate or severe
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NACE Subgroup Analysis
P-VALUES
HAZARD RATIO (95 CI)
Superiority
Interaction
Low (247-544)
0.75 (0.60-0.94)
0.011
Centres annual volume of PCI
Intermediate (548-991)
1.04 (0.82-1.32)
0.76
0.89
High (1000-1950)
0.025
0.75 (0.58-0.97)
Low (14.9-64.4)
Centres Proportion of radial PCI
1.01 (0.79-1.29)
0.95
Intermediate (65.4-79.0)
0.0048
0.71
0.95 (0.75 -1.22)
High (80.0-98.0)
lt0.001
0.64 (0.51-0.80)
STEMI
0.86 (0.68-1.08)
0.19
NSTE-ACS (tp)
ACS type
0.059
0.44
0.58 (0.33-1.03)
0.07
0.85 (0.71-1.02)
NSTE-ACS (tp)
75
0.23
0.88 (0.70-1.09)
Age
0.62
lt75
0.023
0.82 (0.68-0.97)
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
Women
0.012
0.72 (0.56-0.93)
Sex
0.18
0.16
0.89 (0.76-1.05)
Men
25
0.09
0.86 (0.73-1.02)
BMI
0.53
0.038
0.79 (0.63-0.99)
lt25
0.07
0.83 (0.68-1.02)
Ticagrelor or prasugrel
Yes
0.94
0.06
No
0.84 (0.70-1.01)
Yes
0.45
0.91 (0.71-1.17)
Diabetes
0.43
No
0.08
0.80 (0.68-0.94)
60
0.78 (0.65-0.94)
0.01
GFR
0.51
lt60
0.86 (0.70-1.07)
0.18
History of PVD
0.60
0.91 (0.64-1.30)
Yes
0.64
0.012
No
0.83 (0.71-0.96)
2
0.50
1
0.25
Femoral Better
Rardial Better
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Subgroup Analysis
P-VALUES
Mortality
HAZARD RATIO (95 CI)
Superiority
Interaction
1.28 (0.71-2.32)
0.41
Low (14.9-64.4)
Centres Proportion of radial PCI
Intermediate (65.4-79.0)
0.0157
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)
ACS type
0.10
NSTE-ACS (tp)
0.49 (0.28-0.87)
0.012
2
Bleeding
1
0.50
0.25
0.90 (0.54-1.50)
0.68
Low (14.9-64.4)
Centres Proportion of radial PCI
Intermediate (65.4-79.0)
0.06
0.57 (0.31 -1.03)
0.20
High (80.0-98.0)
0.035
0.56 (0.32-0.97)
0.62 (0.41-0.94)
0.022
STEMI
0.54
0.58
ACS type
1.66 (0.28-10.0)
NSTE-ACS (tp)
0.70 (0.42-1.17)
0.17
NSTE-ACS (tp)
2
4
1
0.50
0.25
Femoral Better
Radial Better
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Updated Meta-analysis
19,328 ACS patients being randomly allocated to
radial or femoral access
Heterogenity
SUBGROUP
Risk Ratio (95CI)
P Value
P Value
I2
Non-CABG major bleeds
Pre-Rival
0.41 (0.22-0.76)
0.73 (0.43-1.23)
RIVAL
Post-RIVAL
0.39 (0.23-0.67)
MATRIX
0.68 (0.49-0.92)
Combined
0.58 (0.46-0.72)
lt0.0001
0
0.51
Death, myocardial infarction or stroke
0.82 (0.52-1.29)
Pre-Rival
0.98 (0.76-1.27)
RIVAL
0.67 (0.48-0.93)
Post-RIVAL
MATRIX
0.86 (0.76-0.98)
Combined
0.86 (0.77-0.95)
0.0051
0
0.97
Death
0.77 (0.46-1.28)
Pre-Rival
0.86 (0.58-1.29)
RIVAL
0.58 (0.39-0.87)
Post-RIVAL
0.73 (0.53-0.99)
MATRIX
0.72 (0.60-0.88)
0.0011
Combined
0
1.00
Myocardial Infarction
Pre-Rival
0.73 (0.12-4.47)
RIVAL
0.92 (0.65-1.31)
Post-RIVAL
0.85 (0.39-1.90)
MATRIX
0.91 (0.78-1.06)
Combined
0.91 (0.79-1.04)
0.16
0
0.88
0.26 (0.06-1.23)
Pre-Rival
Stroke
1.43 (0.72-2.83)
RIVAL
1.40 (0.45-4.40)
Post-RIVAL
1.00 (0.50-2.00)
MATRIX
1.05 (0.69-1.60)
0.80
0.75
Combined
0
4
0.50
2
Rardial Better
1
0.25
Femoral Better
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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

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MATRIX Access Program
http//dx.doi.org/10.1016/S0140-6736(15)60507-4