A Randomized Multicentre Trial to Evaluate the
Utilization of Revascularization or Optimal Medical
Therapy for the Treatment of Chronic Total
Coronary Occlusions (EUROCTO-Trial)
Background
•16-‐18% of all coronary lesions in pa3ents with stable coronary artery
disease are chronic total occlusions (CTO)1,2
•Only 5% of PCI is for CTOs; many pa3ents remain untreated3
•In current guidelines CTOs are considered a specific subcategory of
lesions with only a IIa recommenda3on to perform PCI4
Study goals
•This is the first randomised trial to compare the effects of PCI vs
Op3mal medical therapy (OMT) on the 12-‐month health status of
pa3ents with a CTO.
•During longer-‐term follow-‐up the study will also assess the safety at
3 years of PCI as compared to OMT for a CTO in stable coronary artery
disease.
1)Fefer
P et al. J Am Coll Cardiol. 2012;59:991-‐997; 2)Råmunddal T. et Al. PLoS One. 2014;9:e103850; 3)Brilakis E. et al.
JACC Cardiovasc Interv. 2015;8:245-‐53; 4)Windecker S et al. Eur Heart J. 2014;35:2541-‐619
Study design and methods
• 26 European centres with expert CTO operators par3cipated in this
study from 2012-‐2015 organised by the EURO CTO club
• 396 pa3ents with a CTO were randomised 2:1 to receive either PCI
or OMT; pts with mul3-‐vessel disease had their non-‐CTO lesions
treated before randomisa3on
• PCI was performed in 255 of the 259 pa3ents in the PCI group with
a final success rate of 86.3%. (10 of 20 pts underwent a successful
second aaempt).
• In the OMT group 10 pa3ents (7%) crossed over to PCI because of
severe symptoms
• At baseline and at 12-‐month follow-‐up pa3ents filled out SAQ and
EQ-‐5D ques3onnaires to assess their health status. This was the
primary endpoint.
• At 3 years, pa3ents will be assessed as to the safety endpoint of
the trial.
• All events have been adjudicated by a clinical events commiaee
Study flow chart
Multivessel CAD including CTO
29%
Angina or
anginaequivalent
symptoms
Single-vessel disease CTO only
Treat non-occlusive disease
by PCI before CTO with DES
Efficacy: Health status @ 12 and 36 months
Safety: Death, non-fatal myocardial infarction (ITT, PP) @ 36 months
48%
Study flow chart
Multivessel CAD including CTO
29%
Single-vessel disease CTO only
Angina or
anginaequivalent
symptoms
48%
Treat non-occlusive disease
by PCI before CTO with DES
OMT to include:
-Aspirin,
Randomisation 2:1
-Statin,
-ACE-inhibitor where tolerated
11 pats
excluded
PCI with DES
2
1
+ OMT
OMT
n=259
n=137
- + at least 2 anti-anginal agents at
max tolerated dose including ratelimiting agent where appropriate.
Ischaemic symptoms should be
confirmed with non-invasive test.
Efficacy: Health status @ 12 and 36 months
Safety: Death, non-fatal myocardial infarction (ITT, PP) @ 36 months
Study flow chart
Multivessel CAD including CTO
29%
Single-vessel disease CTO only
Angina or
anginaequivalent
symptoms
48%
Treat non-occlusive disease
by PCI before CTO with DES
OMT to include:
-Aspirin,
Randomisation 2:1
-Statin,
-ACE-inhibitor where tolerated
11 pats
excluded
PCI with DES
2
1
+ OMT
OMT
n=259
n=137
Success
Failure
Decision as per
usual clinical care
Medical Rx
CABG
Clinically
indicated
interim PCI
- + at least 2 anti-anginal agents at
max tolerated dose including ratelimiting agent where appropriate.
Ischaemic symptoms should be
confirmed with non-invasive test.
Ongoing angina
despite OMT
n=10 (7.3%)
Repeat Exercise Tolerance Test (ETT) for objective assessment of ischemia @ 12m and 36months
Efficacy: Health status @ 12 and 36 months
Safety: Death, non-fatal myocardial infarction (ITT, PP) @ 36 months
100
Primary endpoint: SAQ health status
OMT
PCI
P=0.019
(ITT)
P=0.061
P=0.63
P=0.040
90
80
P=0.90
70
60
50
40
30
20
10
0
BL FU
BL FU
BL FU
BL FU
BL FU
BL FU
Physical
Anginal
Quality of
limita3on
frequency
life
For mul3ple tes3ng the significance level is 0.01
BL FU
BL FU
Anginal
stability
BL FU
BL FU
Treatment
sa3sfac3on
Summary of key results
• At 12 months, pa3ents who underwent CTO PCI had less angina, less physical
limita3on, and a trend to improved quality of life as assessed by the SAQ.
• At 12 months, pa3ents who underwent CTO PCI had greater mobility, beaer
ac3vity status and less pain or discomfort as assessed by the EQ-‐5D
• There was no change in treatment sa3sfac3on or angina stability (by SAQ),
and no change in anxiety or self-‐care (by EQ-‐5D)
100
80
60
OMT
P=0.004
PCI
P=0.02
• Procedural success rate was 86.3%
P=0.006
• OMT crossover was 7%
P=0.02
• PCI complicaCon rate was 2.9%
40
20
• 1-‐year MACE rate was comparable
0
Physical
Anginal Freedom of Quality of
limita3on frequency angina
life ≥16
≥8
≥20
(100%)
Graph: Significant improvements at 12 months
in SAQ subscales in both study groups;
Higher score, beaer health status
Relevance of this study
• This study was the first to compare PCI and OMT in
the management of a CTO, which is the classical
example of stable coronary artery disease, and assess
the change in health status within a 12 month period
• The improvement of health status shown aier PCI is a
valid clinical goal in trea3ng stable coronary artery
disease
• PCI of a CTO should be considered as a primary op3on
in symptoma3c pa3ents -‐ it is a safe and effec3ve
treatment op3on in expert hands
• The long-‐term safety and sustainability of the results
will be assessed at the 3-‐year follow-‐up
TRIAL ORGANIZATION
PI:
Steering
Committee:
Statistics:
DSMB:
G. S. Werner
E. Christiansen; I. Durand Zaleski; J. Escaned; A. Galassi
A.H. Gershlick; G. Heyndrickx ; D. Hildick-Smith ; Y. Louvard; G.
Olivecrona; G. Sianos; G. S. Werner (Chairperson)
K. Bogaerts (KU Leuven)
M Bertrand (Chair); C. Hamm; J-J. Goy
CEC:
J. Machecourt (Chair), A. Baumbach, J. Garot
CRO:
CERC, Massy, France (Project Leader M. Carvalho)
e-CRF:
Sponsor:
Clinigrid
Euro-CTO Club (grant from Biosensors and Asahi)