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