Results From The Minimizing Adverse Haemorrhagic Events By Transradial … · 2017-07-11 ·...

Results From The Minimizing

Adverse Haemorrhagic Events By

Transradial Access Site And

Systemic Implementation

of Angiox-MATRIX

Treatment Duration Program

M. Valgimigli, MD, PhD

Swiss Cardiovascular Center Bern,

Inselspital, Bern, Switzerland

on behalf of the MATRIX Group

NCT01433627

Declaration of Interest

I, Marco Valgimigli,

Served as a speaker, or advisor or consultant for:

The Medicines Company and Terumo

Background

Bivalirudin reduces bleeding events as compared to

UFH±GPI but it concomitntaly increases

stent thrombosis risk

Bivalirudin label allows continuation of the drug

after PCI at either low (0.25 mg/Kg/h) or full

(1.75 mg/Kg/h) regimen

Whether prolonging bivalirudin after PCI mitigates

ischemic without increasing bleeding risks is

unknown due to lack of properly powered RCTs

Objectives To determine whether the use of bivalirudin during

intervention followed by a post-PCI infusion of ≥4

hours, as compared to no post-PCI infusion, is

associated with reduction in net adverse

cardiovascular events (NACE), defined as the

composite of death, MI, stroke, major bleeding, urgent

TVR and stent thrombosis

To determine the impact of post-PCI bivalirudin

infusion on each components of the primary endpoint

In a broadly inclusive ACS population undergoing

invasive management via randomly assigned radial or

femoral access

1:1

1:1

NSTEACS or STEMI with invasive management Aspirin+P2Y12 blocker

Trans-Femoral Access

Heparin

±GPI

Bivalirudin

Mono-Tx

Stop

Infusion Prolong≥ 4 hs

infusion

1:1

Trans-Radial Access

MATRIX Program NCT01433627

http://www.cardiostudy.it/matrix

Lancet. 2015; 385(9986):2465-76

ACC 2015, oral presentation

Study Organization and Sites

Sponsor

Clinical Event Committee

P. Vranckx, Chair

S. Leonardi Co-Chair

P. Tricoci

Italian Society of Interventional Cardiology

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

3603

allocated to UFH

MATRIX Patient Flow Chart: Treatment Duration program

7213 pts included in the

Anti-thrombin program

3610 pts included in the

Treatment Duration Study

1799 Post-PCI Bivalirudin

93.3% received allocated

Intervention

1811 No post-PCI Bivalirudin

96.8% received allocated

intervention

13 No post-discharge FUP

1790 (99.4%)

Complete 30-day information

1807 (99.8%) Complete 30-day information

Post-PCI Bivalirudin Rx

Bivalirudin could be administered at*:

the full PCI dose (1.75mg/kg/h) for up to 4 hours

or

the reduced dose of 0.25 mg/Kg/h for at least 6 hours

Regimens and temporal distribution

*: with the choice between those two regimens made at the discretion of the treating physicians

Full PCI regimen

Reduced regimen

34.4% Infusion duration: 264’

59% Infusion duration: 433’

N=119 (6.6%) receiving no post-PCI bivalirudin in the post-PCI bivalirudin arm

Primary EP: NACE

11.0%

No post-PCI bivalirudin

Post-PCI bivalirudin

RR: 0.91; 95% CI: 0.74-1.11; P=0.34

11.9%

Treatment Duration Study

1 EP Components Death, MI, Stroke, urg. TVR, ST and BARC 3 or 5

1.6

8.6

0.3

1.7 1.3

1

1.8

8.6

0.4 1.2

0.7

1.8

0

1

2

3

4

5

6

7

8

9

10

Death MI Stroke Urg TVR ST BARC 3 or 5

Post-PCI Biv no Post-PCI Biv

P=0.03

%

0.53

0.30–0.96

P=0.09

1.78

0.90–3.53 P=0.16

1.49

0.85–2.60

P=0.79

0.86

0.29–2.56

P=0.99

P=0.53

0.85

0.51–1.42

Stent Thrombosis Definite and Definite or Probable

0.6 0.7

1.5

0.6

0.8

0.6

0.2

1.1

0.6 0.5

0

0.2

0.4

0.6

0.8

1

1.2

1.4

1.6

Definite Acute Definite Subacute

Def o Prob Overall

Def or Prob Acute

Def or Prob Subacute

Post-PCI Biv no Post-PCI Biv

P=0.14

%

1.89

0.80–4.46

P=0.99

1.01

0.43–2.33

P=0.29

1.38

0.76–2.50

P=0.01

4.37

1.24–15.35

P=0.99

P=0.99

1.01

0.42–2.43

Bleeding BARC, TIMI and GUSTO definitions

5

0.7

0.3

0.8 0.5

3.5

0.4

1.3 1.1

1.3

0

1

2

3

4

5

6

BARC 2 BARC 3/5 AR BARC 3/5 NAR TIMI GUSTO

Post-PCI Biv no Post-PCI Biv

P=0.01

%

0.39

0.18–0.85

P=0.23

0.65

0.32–1.31

P=0.001

0.25

0.10–0.61

P=0.48

1.38

0.56–3.45

P=0.99 P=0.02

1.46

1.05–2.03

Explorative Analysis* Ischemic and Bleeding EPs according to bivalirudin

regimen in the post-PCI bivalirudin arm

11.9

1.8 2.1

0.8 1.2 1.4

4.4

0.8 0.2 0.2 0 0.3

1.8 0.7 0.6

0.2

1.8

0

2

4

6

8

10

12

14

NACE (1 EP) Death Definite ST Acute ST Subacute ST BARC 3 or 5

0.25 Post-PCI Biv

1.75 Post-PCI Biv

no Post-PCI Biv

%

* The choice of post-PCI bivalirudin regimen was at discretion of the investigator

14.7

Summary

The post-PCI infusion of bivalirudin for at least 4

hours after the intervention did not decrease the

composite outcome of ischemic and bleeding

events, including stent thrombosis.

This finding was consistent across subgroups,

including access site.

Post-PCI bivalirudin infusion was safe and

associated to lower risk of major bleeding

according to BARC 3/5 or GUSTO scales.