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