Trial Outcomes & Findings for Comparison Between FFR Guided Revascularization Versus Conventional Strategy in Acute STEMI Patients With MVD. (NCT NCT01399736)

NCT ID: NCT01399736

Last Updated: 2020-08-11

Results Overview

Number of participants with the composite endpoint of all cause mortality non-fatal Myocardial Infarction, any Revascularisation and Cerebrovascular Events (MACCE) at 12 months between groups

• Recruitment status: COMPLETED
• Study phase: NA
• Target enrollment: 885 participants
• Primary outcome timeframe: 12 months
• Results posted on: 2020-08-11

Participant Flow

Participant milestones

Measure	FFR-guided Revascularisation Strategy In the FFR-group all flow limiting (FFR≤0.80) lesions will receive treatment by PCI and stenting. The non-IRA PCI should be performed during the same intervention. Exceptions can be made for complex lesions where the operator estimates that the revascularisation procedure will require significant contrast overload which may lead to deterioration of cardiac and renal function of the patient. Such procedures can be performed in a second procedure which should take place within the same hospitalisation. All lesions with a FFR measurement of \>0.80 will not be treated. FFR-guided revascularisation strategy: FFR-guided revascularisation strategy	Randomised to Guidelines Group In the randomised to guidelines group the procedure will stop after the FFR measurements and the patient will be referred to his treating cardiologist who will decide whether a staged PCI of the non-IRA artery should take place. The treating cardiologist will be blinded for the FFR measurements (but not angiographic imaging) and must make a decision based on conventional non-invasive ischemia detecting tests or clinical signs and symptoms i.e. very typical angina symptoms in patients with angiographic significant stenosis). randomised to guidelines group: Staged revascularisation by proven ischemia or persistence of symptoms of angina
Overall Study STARTED	295	590
Overall Study COMPLETED	291	586
Overall Study NOT COMPLETED	4	4

Reasons for withdrawal

Measure	FFR-guided Revascularisation Strategy In the FFR-group all flow limiting (FFR≤0.80) lesions will receive treatment by PCI and stenting. The non-IRA PCI should be performed during the same intervention. Exceptions can be made for complex lesions where the operator estimates that the revascularisation procedure will require significant contrast overload which may lead to deterioration of cardiac and renal function of the patient. Such procedures can be performed in a second procedure which should take place within the same hospitalisation. All lesions with a FFR measurement of \>0.80 will not be treated. FFR-guided revascularisation strategy: FFR-guided revascularisation strategy	Randomised to Guidelines Group In the randomised to guidelines group the procedure will stop after the FFR measurements and the patient will be referred to his treating cardiologist who will decide whether a staged PCI of the non-IRA artery should take place. The treating cardiologist will be blinded for the FFR measurements (but not angiographic imaging) and must make a decision based on conventional non-invasive ischemia detecting tests or clinical signs and symptoms i.e. very typical angina symptoms in patients with angiographic significant stenosis). randomised to guidelines group: Staged revascularisation by proven ischemia or persistence of symptoms of angina
Overall Study Withdrawal by Subject	4	2
Overall Study Lost to Follow-up	0	2

Baseline Characteristics

information missing for 1 patient

Baseline characteristics by cohort

Measure	FFR-guided Revascularisation Strategy n=295 Participants In the FFR-group all flow limiting (FFR≤0.80) lesions will receive treatment by PCI and stenting. The non-IRA PCI should be performed during the same intervention. Exceptions can be made for complex lesions where the operator estimates that the revascularisation procedure will require significant contrast overload which may lead to deterioration of cardiac and renal function of the patient. Such procedures can be performed in a second procedure which should take place within the same hospitalisation. All lesions with a FFR measurement of \>0.80 will not be treated. FFR-guided revascularisation strategy: FFR-guided revascularisation strategy	Randomised to Guidelines Group n=590 Participants In the randomised to guidelines group the procedure will stop after the FFR measurements and the patient will be referred to his treating cardiologist who will decide whether a staged PCI of the non-IRA artery should take place. The treating cardiologist will be blinded for the FFR measurements (but not angiographic imaging) and must make a decision based on conventional non-invasive ischemia detecting tests or clinical signs and symptoms i.e. very typical angina symptoms in patients with angiographic significant stenosis). randomised to guidelines group: Staged revascularisation by proven ischemia or persistence of symptoms of angina	Total n=885 Participants Total of all reporting groups
Age, Continuous	62 years STANDARD_DEVIATION 10 • n=295 Participants	61 years STANDARD_DEVIATION 10 • n=590 Participants	62 years STANDARD_DEVIATION 10 • n=885 Participants
Sex: Female, Male Female	62 Participants n=295 Participants	140 Participants n=590 Participants	202 Participants n=885 Participants
Sex: Female, Male Male	233 Participants n=295 Participants	450 Participants n=590 Participants	683 Participants n=885 Participants
Race/Ethnicity, Customized white race	263 Participants n=295 Participants • information missing for 1 patient	545 Participants n=589 Participants • information missing for 1 patient	808 Participants n=884 Participants • information missing for 1 patient
Race/Ethnicity, Customized other races	32 Participants n=295 Participants • information missing for 1 patient	44 Participants n=590 Participants • information missing for 1 patient	76 Participants n=885 Participants • information missing for 1 patient
BMI	27.2 kg/m^2 n=295 Participants	27.1 kg/m^2 n=590 Participants	27.1 kg/m^2 n=885 Participants
Diabetes Mellitus	43 Participants n=295 Participants	94 Participants n=590 Participants	137 Participants n=885 Participants
Hypertension	136 Participants n=295 Participants	282 Participants n=590 Participants	418 Participants n=885 Participants
current smoker	120 Participants n=294 Participants • information about smoking missing for few patients	287 Participants n=589 Participants • information about smoking missing for few patients	407 Participants n=883 Participants • information about smoking missing for few patients
Hypercholesterolemia	95 Participants n=295 Participants	176 Participants n=590 Participants	271 Participants n=885 Participants
Family history of premature coronary artery disease	103 Participants n=294 Participants • information missing for 1 patient	223 Participants n=590 Participants • information missing for 1 patient	326 Participants n=884 Participants • information missing for 1 patient
Previous stroke	10 Participants n=295 Participants	26 Participants n=590 Participants	36 Participants n=885 Participants
Previous Myocardial Infarction	22 Participants n=295 Participants	48 Participants n=590 Participants	70 Participants n=885 Participants
Previous PCI	25 Participants n=295 Participants	44 Participants n=590 Participants	69 Participants n=885 Participants
Renal Impairment	3 Participants n=295 Participants	7 Participants n=590 Participants	10 Participants n=885 Participants
Peripheral vessel disease	10 Participants n=295 Participants	23 Participants n=590 Participants	33 Participants n=885 Participants
Location of infarct - Posterior	53 Participants n=295 Participants	96 Participants n=590 Participants	149 Participants n=885 Participants
Location of infarct - Anterior	105 Participants n=295 Participants	206 Participants n=590 Participants	311 Participants n=885 Participants
Location of infarct - Inferior	149 Participants n=295 Participants	307 Participants n=590 Participants	456 Participants n=885 Participants
Location of infarct - Lateral	41 Participants n=295 Participants	86 Participants n=590 Participants	127 Participants n=885 Participants
Location of infarct - impossible to determine	3 Participants n=295 Participants	4 Participants n=590 Participants	7 Participants n=885 Participants
Time from symptom onset to primary PCI < 6 hr	225 Participants n=295 Participants	462 Participants n=590 Participants	687 Participants n=885 Participants
Time from symptom onset to primary PCI 6-12 hr	47 Participants n=295 Participants	84 Participants n=590 Participants	131 Participants n=885 Participants
Time from symptom onset to primary PCI >12 hr	23 Participants n=295 Participants	44 Participants n=590 Participants	67 Participants n=885 Participants
Nr. of arteries with stenosis 2	204 Participants n=295 Participants	396 Participants n=590 Participants	600 Participants n=885 Participants
Nr. of arteries with stenosis 3	91 Participants n=295 Participants	194 Participants n=590 Participants	285 Participants n=885 Participants
Killip class >=2	15 Participants n=295 Participants	30 Participants n=590 Participants	45 Participants n=885 Participants
Maximum creatinine kinase level	1040 IU/liter n=295 Participants	1125 IU/liter n=590 Participants	1083 IU/liter n=885 Participants
Mean time for index procedure - min	65 minutes STANDARD_DEVIATION 31 • n=295 Participants	59 minutes STANDARD_DEVIATION 28 • n=590 Participants	61 minutes STANDARD_DEVIATION 29 • n=885 Participants
Mean volume of contract used during index PCI	224 ml STANDARD_DEVIATION 104 • n=295 Participants	202 ml STANDARD_DEVIATION 75 • n=590 Participants	209 ml STANDARD_DEVIATION 86 • n=885 Participants
FFR procedure successful	292 Participants n=295 Participants	575 Participants n=590 Participants	867 Participants n=885 Participants
Patients with lesions FFR<=0.80	158 Participants n=292 Participants • FFR not performed in all patients	275 Participants n=575 Participants • FFR not performed in all patients	433 Participants n=867 Participants • FFR not performed in all patients
Patients with lesions FFR>0.80	134 Participants n=292 Participants • FFR not performed in all patients	300 Participants n=575 Participants • FFR not performed in all patients	434 Participants n=867 Participants • FFR not performed in all patients
Mean FFR value	0.78 Ratio STANDARD_DEVIATION 0.12 • n=292 Participants • FFR not performed in all patients	0.79 Ratio STANDARD_DEVIATION 0.12 • n=590 Participants • FFR not performed in all patients	0.78 Ratio STANDARD_DEVIATION 0.12 • n=882 Participants • FFR not performed in all patients
Patients with treated (FFR-guided) non-IRA lesions	163 Participants n=295 Participants	0 Participants n=590 Participants	163 Participants n=885 Participants
Patients with treated (FFR-guided) non-IRA lesions during index PCI	136 Participants n=295 Participants	0 Participants n=590 Participants	136 Participants n=885 Participants
Patients with treated (FFR-guided) non-IRA lesions delayed during index hospitalization	27 Participants n=295 Participants	0 Participants n=590 Participants	27 Participants n=885 Participants
Patients with treated (FFR-guided) non-IRA lesions - DES only	161 Participants n=295 Participants	0 Participants n=590 Participants	161 Participants n=885 Participants
Patients with treated (FFR-guided) non-IRA lesions - bare metal stent only	1 Participants n=295 Participants	0 Participants n=590 Participants	1 Participants n=885 Participants
Patients with treated (FFR-guided) non-IRA lesions - balloon dilatation only	1 Participants n=295 Participants	0 Participants n=590 Participants	1 Participants n=885 Participants
Patients with treated (FFR-guided) non-IRA lesions - mean nr. of stents used per patient	1.6 mm STANDARD_DEVIATION 0.9 • n=295 Participants	0 mm STANDARD_DEVIATION 0 • n=590 Participants	1.6 mm STANDARD_DEVIATION 0.9 • n=885 Participants
Patients with treated (FFR-guided) non-IRA lesions -mean length of stent	34.3 mm STANDARD_DEVIATION 21.0 • n=295 Participants	0 mm STANDARD_DEVIATION 0 • n=590 Participants	34.3 mm STANDARD_DEVIATION 21.0 • n=885 Participants
Patients with treated (FFR-guided) non-IRA lesions - mean diameter of stent	2.9 mm STANDARD_DEVIATION 0.4 • n=295 Participants	0 mm STANDARD_DEVIATION 0 • n=590 Participants	2.9 mm STANDARD_DEVIATION 0.4 • n=885 Participants
length of hospital stay	4 days n=295 Participants	4 days n=590 Participants	4 days n=885 Participants
Patients receiving predischarge noninvasive stress tests	21 Participants n=295 Participants	71 Participants n=590 Participants	92 Participants n=885 Participants

PRIMARY outcome

Timeframe: 12 months

Population: Patients with STEMI and multivessel disease

Number of participants with the composite endpoint of all cause mortality non-fatal Myocardial Infarction, any Revascularisation and Cerebrovascular Events (MACCE) at 12 months between groups

Outcome measures

Measure	Randomised to Guidelines Group n=590 Participants In the randomised to guidelines group the procedure will stop after the FFR measurements and the patient will be referred to his treating cardiologist who will decide whether a staged PCI of the non-IRA artery should take place. The treating cardiologist will be blinded for the FFR measurements (but not angiographic imaging) and must make a decision based on conventional non-invasive ischemia detecting tests or clinical signs and symptoms i.e. very typical angina symptoms in patients with angiographic significant stenosis). randomised to guidelines group: Staged revascularisation by proven ischemia or persistence of symptoms of angina	FFR-guided Revascularisation Strategy n=295 Participants In the FFR-group all flow limiting (FFR≤0.80) lesions will receive treatment by PCI and stenting. The non-IRA PCI should be performed during the same intervention. Exceptions can be made for complex lesions where the operator estimates that the revascularisation procedure will require significant contrast overload which may lead to deterioration of cardiac and renal function of the patient. Such procedures can be performed in a second procedure which should take place within the same hospitalisation. All lesions with a FFR measurement of \>0.80 will not be treated. FFR-guided revascularisation strategy: FFR-guided revascularisation strategy
Number of Participants With the Composite Endpoint of MACCE	121 Participants	23 Participants

PRIMARY outcome

Timeframe: 12 months

Population: Patients with STEMI and multivessel disease

Number of participants with all cause mortality at 12 months between groups

Outcome measures

Measure	Randomised to Guidelines Group n=590 Participants In the randomised to guidelines group the procedure will stop after the FFR measurements and the patient will be referred to his treating cardiologist who will decide whether a staged PCI of the non-IRA artery should take place. The treating cardiologist will be blinded for the FFR measurements (but not angiographic imaging) and must make a decision based on conventional non-invasive ischemia detecting tests or clinical signs and symptoms i.e. very typical angina symptoms in patients with angiographic significant stenosis). randomised to guidelines group: Staged revascularisation by proven ischemia or persistence of symptoms of angina	FFR-guided Revascularisation Strategy n=295 Participants In the FFR-group all flow limiting (FFR≤0.80) lesions will receive treatment by PCI and stenting. The non-IRA PCI should be performed during the same intervention. Exceptions can be made for complex lesions where the operator estimates that the revascularisation procedure will require significant contrast overload which may lead to deterioration of cardiac and renal function of the patient. Such procedures can be performed in a second procedure which should take place within the same hospitalisation. All lesions with a FFR measurement of \>0.80 will not be treated. FFR-guided revascularisation strategy: FFR-guided revascularisation strategy
Number of Participants With Death From Any Cause	10 Participants	4 Participants

PRIMARY outcome

Timeframe: 12 months

Population: Patients with STEMI and multivessel disease

Number of participants with Cardiac mortality at 12 months between groups

Outcome measures

Measure	Randomised to Guidelines Group n=590 Participants In the randomised to guidelines group the procedure will stop after the FFR measurements and the patient will be referred to his treating cardiologist who will decide whether a staged PCI of the non-IRA artery should take place. The treating cardiologist will be blinded for the FFR measurements (but not angiographic imaging) and must make a decision based on conventional non-invasive ischemia detecting tests or clinical signs and symptoms i.e. very typical angina symptoms in patients with angiographic significant stenosis). randomised to guidelines group: Staged revascularisation by proven ischemia or persistence of symptoms of angina	FFR-guided Revascularisation Strategy n=295 Participants In the FFR-group all flow limiting (FFR≤0.80) lesions will receive treatment by PCI and stenting. The non-IRA PCI should be performed during the same intervention. Exceptions can be made for complex lesions where the operator estimates that the revascularisation procedure will require significant contrast overload which may lead to deterioration of cardiac and renal function of the patient. Such procedures can be performed in a second procedure which should take place within the same hospitalisation. All lesions with a FFR measurement of \>0.80 will not be treated. FFR-guided revascularisation strategy: FFR-guided revascularisation strategy
Number of Participants With Cardiac Death	6 Participants	3 Participants

PRIMARY outcome

Timeframe: 12 months

Population: Patients with STEMI and multivessel disease

Number of participants with Spontaneous Myocardial Infarction at 12 months between groups

Outcome measures

Measure	Randomised to Guidelines Group n=590 Participants In the randomised to guidelines group the procedure will stop after the FFR measurements and the patient will be referred to his treating cardiologist who will decide whether a staged PCI of the non-IRA artery should take place. The treating cardiologist will be blinded for the FFR measurements (but not angiographic imaging) and must make a decision based on conventional non-invasive ischemia detecting tests or clinical signs and symptoms i.e. very typical angina symptoms in patients with angiographic significant stenosis). randomised to guidelines group: Staged revascularisation by proven ischemia or persistence of symptoms of angina	FFR-guided Revascularisation Strategy n=295 Participants In the FFR-group all flow limiting (FFR≤0.80) lesions will receive treatment by PCI and stenting. The non-IRA PCI should be performed during the same intervention. Exceptions can be made for complex lesions where the operator estimates that the revascularisation procedure will require significant contrast overload which may lead to deterioration of cardiac and renal function of the patient. Such procedures can be performed in a second procedure which should take place within the same hospitalisation. All lesions with a FFR measurement of \>0.80 will not be treated. FFR-guided revascularisation strategy: FFR-guided revascularisation strategy
Number of Participants With Spontaneous MI	17 Participants	5 Participants

PRIMARY outcome

Timeframe: 12 months

Population: Patients with STEMI and multivessel disease

Number of participants with Periprocedural Myocardial Infarction at 12 months between groups

Outcome measures

Measure	Randomised to Guidelines Group n=590 Participants In the randomised to guidelines group the procedure will stop after the FFR measurements and the patient will be referred to his treating cardiologist who will decide whether a staged PCI of the non-IRA artery should take place. The treating cardiologist will be blinded for the FFR measurements (but not angiographic imaging) and must make a decision based on conventional non-invasive ischemia detecting tests or clinical signs and symptoms i.e. very typical angina symptoms in patients with angiographic significant stenosis). randomised to guidelines group: Staged revascularisation by proven ischemia or persistence of symptoms of angina	FFR-guided Revascularisation Strategy n=295 Participants In the FFR-group all flow limiting (FFR≤0.80) lesions will receive treatment by PCI and stenting. The non-IRA PCI should be performed during the same intervention. Exceptions can be made for complex lesions where the operator estimates that the revascularisation procedure will require significant contrast overload which may lead to deterioration of cardiac and renal function of the patient. Such procedures can be performed in a second procedure which should take place within the same hospitalisation. All lesions with a FFR measurement of \>0.80 will not be treated. FFR-guided revascularisation strategy: FFR-guided revascularisation strategy
Number of Participants With Periprocedural MI	11 Participants	2 Participants

PRIMARY outcome

Timeframe: 12 months

Population: Patients with STEMI and multivessel disease

Number of participants with revascularization PCI at 12 months between groups

Outcome measures

Measure	Randomised to Guidelines Group n=590 Participants In the randomised to guidelines group the procedure will stop after the FFR measurements and the patient will be referred to his treating cardiologist who will decide whether a staged PCI of the non-IRA artery should take place. The treating cardiologist will be blinded for the FFR measurements (but not angiographic imaging) and must make a decision based on conventional non-invasive ischemia detecting tests or clinical signs and symptoms i.e. very typical angina symptoms in patients with angiographic significant stenosis). randomised to guidelines group: Staged revascularisation by proven ischemia or persistence of symptoms of angina	FFR-guided Revascularisation Strategy n=295 Participants In the FFR-group all flow limiting (FFR≤0.80) lesions will receive treatment by PCI and stenting. The non-IRA PCI should be performed during the same intervention. Exceptions can be made for complex lesions where the operator estimates that the revascularisation procedure will require significant contrast overload which may lead to deterioration of cardiac and renal function of the patient. Such procedures can be performed in a second procedure which should take place within the same hospitalisation. All lesions with a FFR measurement of \>0.80 will not be treated. FFR-guided revascularisation strategy: FFR-guided revascularisation strategy
Number of Participants With Revascularization - PCI	98 Participants	15 Participants

PRIMARY outcome

Timeframe: 12 months

Population: Patients with STEMI and multivessel disease

Number of participants with revascularization CABG at 12 months between groups

Outcome measures

Measure	Randomised to Guidelines Group n=590 Participants In the randomised to guidelines group the procedure will stop after the FFR measurements and the patient will be referred to his treating cardiologist who will decide whether a staged PCI of the non-IRA artery should take place. The treating cardiologist will be blinded for the FFR measurements (but not angiographic imaging) and must make a decision based on conventional non-invasive ischemia detecting tests or clinical signs and symptoms i.e. very typical angina symptoms in patients with angiographic significant stenosis). randomised to guidelines group: Staged revascularisation by proven ischemia or persistence of symptoms of angina	FFR-guided Revascularisation Strategy n=295 Participants In the FFR-group all flow limiting (FFR≤0.80) lesions will receive treatment by PCI and stenting. The non-IRA PCI should be performed during the same intervention. Exceptions can be made for complex lesions where the operator estimates that the revascularisation procedure will require significant contrast overload which may lead to deterioration of cardiac and renal function of the patient. Such procedures can be performed in a second procedure which should take place within the same hospitalisation. All lesions with a FFR measurement of \>0.80 will not be treated. FFR-guided revascularisation strategy: FFR-guided revascularisation strategy
Number of Participants With Revascularization - CABG	5 Participants	3 Participants

PRIMARY outcome

Timeframe: 12 months

Population: Patients with STEMI and multivessel disease

Number of participants with Cerebrovascular event at 12 months between groups

Outcome measures

Measure	Randomised to Guidelines Group n=590 Participants In the randomised to guidelines group the procedure will stop after the FFR measurements and the patient will be referred to his treating cardiologist who will decide whether a staged PCI of the non-IRA artery should take place. The treating cardiologist will be blinded for the FFR measurements (but not angiographic imaging) and must make a decision based on conventional non-invasive ischemia detecting tests or clinical signs and symptoms i.e. very typical angina symptoms in patients with angiographic significant stenosis). randomised to guidelines group: Staged revascularisation by proven ischemia or persistence of symptoms of angina	FFR-guided Revascularisation Strategy n=295 Participants In the FFR-group all flow limiting (FFR≤0.80) lesions will receive treatment by PCI and stenting. The non-IRA PCI should be performed during the same intervention. Exceptions can be made for complex lesions where the operator estimates that the revascularisation procedure will require significant contrast overload which may lead to deterioration of cardiac and renal function of the patient. Such procedures can be performed in a second procedure which should take place within the same hospitalisation. All lesions with a FFR measurement of \>0.80 will not be treated. FFR-guided revascularisation strategy: FFR-guided revascularisation strategy
Number of Participants With Cerebrovascular Event	4 Participants	0 Participants

SECONDARY outcome

Timeframe: 12 months

Number of participants with Composite endpoint of Cardiac death, Myocardial Infarction, any Revascularisation, Stroke and Major bleeding at 12 months (NACE i.e. Net Adverse Clinical Events)

Outcome measures

Measure	Randomised to Guidelines Group n=590 Participants In the randomised to guidelines group the procedure will stop after the FFR measurements and the patient will be referred to his treating cardiologist who will decide whether a staged PCI of the non-IRA artery should take place. The treating cardiologist will be blinded for the FFR measurements (but not angiographic imaging) and must make a decision based on conventional non-invasive ischemia detecting tests or clinical signs and symptoms i.e. very typical angina symptoms in patients with angiographic significant stenosis). randomised to guidelines group: Staged revascularisation by proven ischemia or persistence of symptoms of angina	FFR-guided Revascularisation Strategy n=295 Participants In the FFR-group all flow limiting (FFR≤0.80) lesions will receive treatment by PCI and stenting. The non-IRA PCI should be performed during the same intervention. Exceptions can be made for complex lesions where the operator estimates that the revascularisation procedure will require significant contrast overload which may lead to deterioration of cardiac and renal function of the patient. Such procedures can be performed in a second procedure which should take place within the same hospitalisation. All lesions with a FFR measurement of \>0.80 will not be treated. FFR-guided revascularisation strategy: FFR-guided revascularisation strategy
Number of Participants With Composite Endpoint of NACE (Any First Event)	174 Participants	25 Participants

SECONDARY outcome

Timeframe: 12 months

Number of participants with Part of composite NACE-Death from any cause or Myocardial Infarction at 12 months

Outcome measures

Measure	Randomised to Guidelines Group n=590 Participants In the randomised to guidelines group the procedure will stop after the FFR measurements and the patient will be referred to his treating cardiologist who will decide whether a staged PCI of the non-IRA artery should take place. The treating cardiologist will be blinded for the FFR measurements (but not angiographic imaging) and must make a decision based on conventional non-invasive ischemia detecting tests or clinical signs and symptoms i.e. very typical angina symptoms in patients with angiographic significant stenosis). randomised to guidelines group: Staged revascularisation by proven ischemia or persistence of symptoms of angina	FFR-guided Revascularisation Strategy n=295 Participants In the FFR-group all flow limiting (FFR≤0.80) lesions will receive treatment by PCI and stenting. The non-IRA PCI should be performed during the same intervention. Exceptions can be made for complex lesions where the operator estimates that the revascularisation procedure will require significant contrast overload which may lead to deterioration of cardiac and renal function of the patient. Such procedures can be performed in a second procedure which should take place within the same hospitalisation. All lesions with a FFR measurement of \>0.80 will not be treated. FFR-guided revascularisation strategy: FFR-guided revascularisation strategy
Number of Participants With Death From Any Cause or MI	38 Participants	11 Participants

SECONDARY outcome

Timeframe: 12 months

Number of participants with Major bleeding at 12 months - Part of composite NACE

Outcome measures

Measure	Randomised to Guidelines Group n=590 Participants In the randomised to guidelines group the procedure will stop after the FFR measurements and the patient will be referred to his treating cardiologist who will decide whether a staged PCI of the non-IRA artery should take place. The treating cardiologist will be blinded for the FFR measurements (but not angiographic imaging) and must make a decision based on conventional non-invasive ischemia detecting tests or clinical signs and symptoms i.e. very typical angina symptoms in patients with angiographic significant stenosis). randomised to guidelines group: Staged revascularisation by proven ischemia or persistence of symptoms of angina	FFR-guided Revascularisation Strategy n=295 Participants In the FFR-group all flow limiting (FFR≤0.80) lesions will receive treatment by PCI and stenting. The non-IRA PCI should be performed during the same intervention. Exceptions can be made for complex lesions where the operator estimates that the revascularisation procedure will require significant contrast overload which may lead to deterioration of cardiac and renal function of the patient. Such procedures can be performed in a second procedure which should take place within the same hospitalisation. All lesions with a FFR measurement of \>0.80 will not be treated. FFR-guided revascularisation strategy: FFR-guided revascularisation strategy
Number of Participants With Major Bleeding	8 Participants	3 Participants

SECONDARY outcome

Timeframe: 12 months

Number of participants with any bleeding at 12 months - part of composite endpoint NACE

Outcome measures

Measure	Randomised to Guidelines Group n=590 Participants In the randomised to guidelines group the procedure will stop after the FFR measurements and the patient will be referred to his treating cardiologist who will decide whether a staged PCI of the non-IRA artery should take place. The treating cardiologist will be blinded for the FFR measurements (but not angiographic imaging) and must make a decision based on conventional non-invasive ischemia detecting tests or clinical signs and symptoms i.e. very typical angina symptoms in patients with angiographic significant stenosis). randomised to guidelines group: Staged revascularisation by proven ischemia or persistence of symptoms of angina	FFR-guided Revascularisation Strategy n=295 Participants In the FFR-group all flow limiting (FFR≤0.80) lesions will receive treatment by PCI and stenting. The non-IRA PCI should be performed during the same intervention. Exceptions can be made for complex lesions where the operator estimates that the revascularisation procedure will require significant contrast overload which may lead to deterioration of cardiac and renal function of the patient. Such procedures can be performed in a second procedure which should take place within the same hospitalisation. All lesions with a FFR measurement of \>0.80 will not be treated. FFR-guided revascularisation strategy: FFR-guided revascularisation strategy
Number of Participants With Any Bleeding at 12 Months	28 Participants	9 Participants

SECONDARY outcome

Timeframe: 48 hours

Number of participants with any bleeding at 48 hours - part of composite endpoint NACE

Outcome measures

Measure	Randomised to Guidelines Group n=590 Participants In the randomised to guidelines group the procedure will stop after the FFR measurements and the patient will be referred to his treating cardiologist who will decide whether a staged PCI of the non-IRA artery should take place. The treating cardiologist will be blinded for the FFR measurements (but not angiographic imaging) and must make a decision based on conventional non-invasive ischemia detecting tests or clinical signs and symptoms i.e. very typical angina symptoms in patients with angiographic significant stenosis). randomised to guidelines group: Staged revascularisation by proven ischemia or persistence of symptoms of angina	FFR-guided Revascularisation Strategy n=295 Participants In the FFR-group all flow limiting (FFR≤0.80) lesions will receive treatment by PCI and stenting. The non-IRA PCI should be performed during the same intervention. Exceptions can be made for complex lesions where the operator estimates that the revascularisation procedure will require significant contrast overload which may lead to deterioration of cardiac and renal function of the patient. Such procedures can be performed in a second procedure which should take place within the same hospitalisation. All lesions with a FFR measurement of \>0.80 will not be treated. FFR-guided revascularisation strategy: FFR-guided revascularisation strategy
Number of Participants With Any Bleeding at 48 Hours	8 Participants	5 Participants

SECONDARY outcome

Timeframe: 12 months

Number of participants with hospitalization for heart failure, unstable angina or chest pain

Outcome measures

Measure	Randomised to Guidelines Group n=590 Participants In the randomised to guidelines group the procedure will stop after the FFR measurements and the patient will be referred to his treating cardiologist who will decide whether a staged PCI of the non-IRA artery should take place. The treating cardiologist will be blinded for the FFR measurements (but not angiographic imaging) and must make a decision based on conventional non-invasive ischemia detecting tests or clinical signs and symptoms i.e. very typical angina symptoms in patients with angiographic significant stenosis). randomised to guidelines group: Staged revascularisation by proven ischemia or persistence of symptoms of angina	FFR-guided Revascularisation Strategy n=295 Participants In the FFR-group all flow limiting (FFR≤0.80) lesions will receive treatment by PCI and stenting. The non-IRA PCI should be performed during the same intervention. Exceptions can be made for complex lesions where the operator estimates that the revascularisation procedure will require significant contrast overload which may lead to deterioration of cardiac and renal function of the patient. Such procedures can be performed in a second procedure which should take place within the same hospitalisation. All lesions with a FFR measurement of \>0.80 will not be treated. FFR-guided revascularisation strategy: FFR-guided revascularisation strategy
Number of Participants With Hospitalization	47 Participants	13 Participants

SECONDARY outcome

Timeframe: 12 months

Number of participants with any revascularization-Part of composite endpoint NACE

Outcome measures

Measure	Randomised to Guidelines Group n=590 Participants In the randomised to guidelines group the procedure will stop after the FFR measurements and the patient will be referred to his treating cardiologist who will decide whether a staged PCI of the non-IRA artery should take place. The treating cardiologist will be blinded for the FFR measurements (but not angiographic imaging) and must make a decision based on conventional non-invasive ischemia detecting tests or clinical signs and symptoms i.e. very typical angina symptoms in patients with angiographic significant stenosis). randomised to guidelines group: Staged revascularisation by proven ischemia or persistence of symptoms of angina	FFR-guided Revascularisation Strategy n=295 Participants In the FFR-group all flow limiting (FFR≤0.80) lesions will receive treatment by PCI and stenting. The non-IRA PCI should be performed during the same intervention. Exceptions can be made for complex lesions where the operator estimates that the revascularisation procedure will require significant contrast overload which may lead to deterioration of cardiac and renal function of the patient. Such procedures can be performed in a second procedure which should take place within the same hospitalisation. All lesions with a FFR measurement of \>0.80 will not be treated. FFR-guided revascularisation strategy: FFR-guided revascularisation strategy
Number of Participants With Revascularization	161 Participants	19 Participants

SECONDARY outcome

Timeframe: 12 months

Number of participants with Stent Thrombosis - Part of composite endpoint NACE

Outcome measures

Measure	Randomised to Guidelines Group n=590 Participants In the randomised to guidelines group the procedure will stop after the FFR measurements and the patient will be referred to his treating cardiologist who will decide whether a staged PCI of the non-IRA artery should take place. The treating cardiologist will be blinded for the FFR measurements (but not angiographic imaging) and must make a decision based on conventional non-invasive ischemia detecting tests or clinical signs and symptoms i.e. very typical angina symptoms in patients with angiographic significant stenosis). randomised to guidelines group: Staged revascularisation by proven ischemia or persistence of symptoms of angina	FFR-guided Revascularisation Strategy n=295 Participants In the FFR-group all flow limiting (FFR≤0.80) lesions will receive treatment by PCI and stenting. The non-IRA PCI should be performed during the same intervention. Exceptions can be made for complex lesions where the operator estimates that the revascularisation procedure will require significant contrast overload which may lead to deterioration of cardiac and renal function of the patient. Such procedures can be performed in a second procedure which should take place within the same hospitalisation. All lesions with a FFR measurement of \>0.80 will not be treated. FFR-guided revascularisation strategy: FFR-guided revascularisation strategy
Number of Participants With Stent Thrombosis	1 Participants	2 Participants

SECONDARY outcome

Timeframe: 3 year

Number of participants with Composite primary endpoint MACCE (any first event) at 3 year

Outcome measures

Measure	Randomised to Guidelines Group n=590 Participants In the randomised to guidelines group the procedure will stop after the FFR measurements and the patient will be referred to his treating cardiologist who will decide whether a staged PCI of the non-IRA artery should take place. The treating cardiologist will be blinded for the FFR measurements (but not angiographic imaging) and must make a decision based on conventional non-invasive ischemia detecting tests or clinical signs and symptoms i.e. very typical angina symptoms in patients with angiographic significant stenosis). randomised to guidelines group: Staged revascularisation by proven ischemia or persistence of symptoms of angina	FFR-guided Revascularisation Strategy n=295 Participants In the FFR-group all flow limiting (FFR≤0.80) lesions will receive treatment by PCI and stenting. The non-IRA PCI should be performed during the same intervention. Exceptions can be made for complex lesions where the operator estimates that the revascularisation procedure will require significant contrast overload which may lead to deterioration of cardiac and renal function of the patient. Such procedures can be performed in a second procedure which should take place within the same hospitalisation. All lesions with a FFR measurement of \>0.80 will not be treated. FFR-guided revascularisation strategy: FFR-guided revascularisation strategy
Number of Participants With Primary Endpoint Outcome MACCE (Any First Event) at 3 Year	178 Participants	46 Participants

SECONDARY outcome

Timeframe: 3 year

Number of participants with Composite endpoint MACCE (any first event) at 3 year - all cause death

Outcome measures

Measure	Randomised to Guidelines Group n=590 Participants In the randomised to guidelines group the procedure will stop after the FFR measurements and the patient will be referred to his treating cardiologist who will decide whether a staged PCI of the non-IRA artery should take place. The treating cardiologist will be blinded for the FFR measurements (but not angiographic imaging) and must make a decision based on conventional non-invasive ischemia detecting tests or clinical signs and symptoms i.e. very typical angina symptoms in patients with angiographic significant stenosis). randomised to guidelines group: Staged revascularisation by proven ischemia or persistence of symptoms of angina	FFR-guided Revascularisation Strategy n=295 Participants In the FFR-group all flow limiting (FFR≤0.80) lesions will receive treatment by PCI and stenting. The non-IRA PCI should be performed during the same intervention. Exceptions can be made for complex lesions where the operator estimates that the revascularisation procedure will require significant contrast overload which may lead to deterioration of cardiac and renal function of the patient. Such procedures can be performed in a second procedure which should take place within the same hospitalisation. All lesions with a FFR measurement of \>0.80 will not be treated. FFR-guided revascularisation strategy: FFR-guided revascularisation strategy
Number of Participants With All Cause Death at 3 Year	21 Participants	9 Participants

SECONDARY outcome

Timeframe: 3 year

Number of participants with Composite endpoint MACCE (any first event) at 3 year - Cardiac death

Outcome measures

Measure	Randomised to Guidelines Group n=590 Participants In the randomised to guidelines group the procedure will stop after the FFR measurements and the patient will be referred to his treating cardiologist who will decide whether a staged PCI of the non-IRA artery should take place. The treating cardiologist will be blinded for the FFR measurements (but not angiographic imaging) and must make a decision based on conventional non-invasive ischemia detecting tests or clinical signs and symptoms i.e. very typical angina symptoms in patients with angiographic significant stenosis). randomised to guidelines group: Staged revascularisation by proven ischemia or persistence of symptoms of angina	FFR-guided Revascularisation Strategy n=295 Participants In the FFR-group all flow limiting (FFR≤0.80) lesions will receive treatment by PCI and stenting. The non-IRA PCI should be performed during the same intervention. Exceptions can be made for complex lesions where the operator estimates that the revascularisation procedure will require significant contrast overload which may lead to deterioration of cardiac and renal function of the patient. Such procedures can be performed in a second procedure which should take place within the same hospitalisation. All lesions with a FFR measurement of \>0.80 will not be treated. FFR-guided revascularisation strategy: FFR-guided revascularisation strategy
Number of Participants With Cardiac Death at 3 Year	8 Participants	5 Participants

SECONDARY outcome

Timeframe: 3 year

Number of participants with Composite endpoint MACCE (any first event) at 3 year - Spontaneous MI

Outcome measures

Measure	Randomised to Guidelines Group n=590 Participants In the randomised to guidelines group the procedure will stop after the FFR measurements and the patient will be referred to his treating cardiologist who will decide whether a staged PCI of the non-IRA artery should take place. The treating cardiologist will be blinded for the FFR measurements (but not angiographic imaging) and must make a decision based on conventional non-invasive ischemia detecting tests or clinical signs and symptoms i.e. very typical angina symptoms in patients with angiographic significant stenosis). randomised to guidelines group: Staged revascularisation by proven ischemia or persistence of symptoms of angina	FFR-guided Revascularisation Strategy n=295 Participants In the FFR-group all flow limiting (FFR≤0.80) lesions will receive treatment by PCI and stenting. The non-IRA PCI should be performed during the same intervention. Exceptions can be made for complex lesions where the operator estimates that the revascularisation procedure will require significant contrast overload which may lead to deterioration of cardiac and renal function of the patient. Such procedures can be performed in a second procedure which should take place within the same hospitalisation. All lesions with a FFR measurement of \>0.80 will not be treated. FFR-guided revascularisation strategy: FFR-guided revascularisation strategy
Number of Participants With Spontaneous MI at 3 Year	40 Participants	17 Participants

SECONDARY outcome

Timeframe: 3 year

Number of participants with Composite endpoint MACCE (any first event) at 3 year - Peri-procedural MI

Outcome measures

Measure	Randomised to Guidelines Group n=590 Participants In the randomised to guidelines group the procedure will stop after the FFR measurements and the patient will be referred to his treating cardiologist who will decide whether a staged PCI of the non-IRA artery should take place. The treating cardiologist will be blinded for the FFR measurements (but not angiographic imaging) and must make a decision based on conventional non-invasive ischemia detecting tests or clinical signs and symptoms i.e. very typical angina symptoms in patients with angiographic significant stenosis). randomised to guidelines group: Staged revascularisation by proven ischemia or persistence of symptoms of angina	FFR-guided Revascularisation Strategy n=295 Participants In the FFR-group all flow limiting (FFR≤0.80) lesions will receive treatment by PCI and stenting. The non-IRA PCI should be performed during the same intervention. Exceptions can be made for complex lesions where the operator estimates that the revascularisation procedure will require significant contrast overload which may lead to deterioration of cardiac and renal function of the patient. Such procedures can be performed in a second procedure which should take place within the same hospitalisation. All lesions with a FFR measurement of \>0.80 will not be treated. FFR-guided revascularisation strategy: FFR-guided revascularisation strategy
Number of Participants With Peri-procedural MI at 3 Year	13 Participants	3 Participants

SECONDARY outcome

Timeframe: 3 year

Number of participants with Composite endpoint MACCE (any first event) at 3 year - urgent revascularisation

Outcome measures

Measure	Randomised to Guidelines Group n=590 Participants In the randomised to guidelines group the procedure will stop after the FFR measurements and the patient will be referred to his treating cardiologist who will decide whether a staged PCI of the non-IRA artery should take place. The treating cardiologist will be blinded for the FFR measurements (but not angiographic imaging) and must make a decision based on conventional non-invasive ischemia detecting tests or clinical signs and symptoms i.e. very typical angina symptoms in patients with angiographic significant stenosis). randomised to guidelines group: Staged revascularisation by proven ischemia or persistence of symptoms of angina	FFR-guided Revascularisation Strategy n=295 Participants In the FFR-group all flow limiting (FFR≤0.80) lesions will receive treatment by PCI and stenting. The non-IRA PCI should be performed during the same intervention. Exceptions can be made for complex lesions where the operator estimates that the revascularisation procedure will require significant contrast overload which may lead to deterioration of cardiac and renal function of the patient. Such procedures can be performed in a second procedure which should take place within the same hospitalisation. All lesions with a FFR measurement of \>0.80 will not be treated. FFR-guided revascularisation strategy: FFR-guided revascularisation strategy
Number of Participants With Urgent Revascularization at 3 Year	85 Participants	22 Participants

SECONDARY outcome

Timeframe: 3 year

Number of participants with Composite endpoint MACCE (any first event) at 3 year -elective revascularisation

Outcome measures

Measure	Randomised to Guidelines Group n=590 Participants In the randomised to guidelines group the procedure will stop after the FFR measurements and the patient will be referred to his treating cardiologist who will decide whether a staged PCI of the non-IRA artery should take place. The treating cardiologist will be blinded for the FFR measurements (but not angiographic imaging) and must make a decision based on conventional non-invasive ischemia detecting tests or clinical signs and symptoms i.e. very typical angina symptoms in patients with angiographic significant stenosis). randomised to guidelines group: Staged revascularisation by proven ischemia or persistence of symptoms of angina	FFR-guided Revascularisation Strategy n=295 Participants In the FFR-group all flow limiting (FFR≤0.80) lesions will receive treatment by PCI and stenting. The non-IRA PCI should be performed during the same intervention. Exceptions can be made for complex lesions where the operator estimates that the revascularisation procedure will require significant contrast overload which may lead to deterioration of cardiac and renal function of the patient. Such procedures can be performed in a second procedure which should take place within the same hospitalisation. All lesions with a FFR measurement of \>0.80 will not be treated. FFR-guided revascularisation strategy: FFR-guided revascularisation strategy
Number of Participants With Elective Revascularization at 3 Year	64 Participants	15 Participants

SECONDARY outcome

Timeframe: 3 year

Number of participants with Composite endpoint MACCE (any first event) at 3 year -Cerebrovascular event

Outcome measures

Measure	Randomised to Guidelines Group n=590 Participants In the randomised to guidelines group the procedure will stop after the FFR measurements and the patient will be referred to his treating cardiologist who will decide whether a staged PCI of the non-IRA artery should take place. The treating cardiologist will be blinded for the FFR measurements (but not angiographic imaging) and must make a decision based on conventional non-invasive ischemia detecting tests or clinical signs and symptoms i.e. very typical angina symptoms in patients with angiographic significant stenosis). randomised to guidelines group: Staged revascularisation by proven ischemia or persistence of symptoms of angina	FFR-guided Revascularisation Strategy n=295 Participants In the FFR-group all flow limiting (FFR≤0.80) lesions will receive treatment by PCI and stenting. The non-IRA PCI should be performed during the same intervention. Exceptions can be made for complex lesions where the operator estimates that the revascularisation procedure will require significant contrast overload which may lead to deterioration of cardiac and renal function of the patient. Such procedures can be performed in a second procedure which should take place within the same hospitalisation. All lesions with a FFR measurement of \>0.80 will not be treated. FFR-guided revascularisation strategy: FFR-guided revascularisation strategy
Number of Participants With Cerebrovascular Event	7 Participants	1 Participants

SECONDARY outcome

Timeframe: 3 years

Number of participants with Composite endpoint of Cardiac death, Myocardial Infarction, any Revascularisation, Stroke and Major bleeding at 3 year (NACE i.e. Net Adverse Clinical Events)

Outcome measures

Measure	Randomised to Guidelines Group n=590 Participants In the randomised to guidelines group the procedure will stop after the FFR measurements and the patient will be referred to his treating cardiologist who will decide whether a staged PCI of the non-IRA artery should take place. The treating cardiologist will be blinded for the FFR measurements (but not angiographic imaging) and must make a decision based on conventional non-invasive ischemia detecting tests or clinical signs and symptoms i.e. very typical angina symptoms in patients with angiographic significant stenosis). randomised to guidelines group: Staged revascularisation by proven ischemia or persistence of symptoms of angina	FFR-guided Revascularisation Strategy n=295 Participants In the FFR-group all flow limiting (FFR≤0.80) lesions will receive treatment by PCI and stenting. The non-IRA PCI should be performed during the same intervention. Exceptions can be made for complex lesions where the operator estimates that the revascularisation procedure will require significant contrast overload which may lead to deterioration of cardiac and renal function of the patient. Such procedures can be performed in a second procedure which should take place within the same hospitalisation. All lesions with a FFR measurement of \>0.80 will not be treated. FFR-guided revascularisation strategy: FFR-guided revascularisation strategy
Number of Participants With Composite Endpoint of NACE (Any First Event) at 3 Year	215 Participants	45 Participants

SECONDARY outcome

Timeframe: 3 year

Number of participants with Part of composite NACE-Death from any cause or Myocardial Infarction at 3 year

Outcome measures

Measure	Randomised to Guidelines Group n=590 Participants In the randomised to guidelines group the procedure will stop after the FFR measurements and the patient will be referred to his treating cardiologist who will decide whether a staged PCI of the non-IRA artery should take place. The treating cardiologist will be blinded for the FFR measurements (but not angiographic imaging) and must make a decision based on conventional non-invasive ischemia detecting tests or clinical signs and symptoms i.e. very typical angina symptoms in patients with angiographic significant stenosis). randomised to guidelines group: Staged revascularisation by proven ischemia or persistence of symptoms of angina	FFR-guided Revascularisation Strategy n=295 Participants In the FFR-group all flow limiting (FFR≤0.80) lesions will receive treatment by PCI and stenting. The non-IRA PCI should be performed during the same intervention. Exceptions can be made for complex lesions where the operator estimates that the revascularisation procedure will require significant contrast overload which may lead to deterioration of cardiac and renal function of the patient. Such procedures can be performed in a second procedure which should take place within the same hospitalisation. All lesions with a FFR measurement of \>0.80 will not be treated. FFR-guided revascularisation strategy: FFR-guided revascularisation strategy
Number of Participants With Death From Any Cause or MI	73 Participants	28 Participants

SECONDARY outcome

Timeframe: 3 year

Number of participants with Part of composite endpoint NACE- Major bleeding at 3 year

Outcome measures

Measure	Randomised to Guidelines Group n=590 Participants In the randomised to guidelines group the procedure will stop after the FFR measurements and the patient will be referred to his treating cardiologist who will decide whether a staged PCI of the non-IRA artery should take place. The treating cardiologist will be blinded for the FFR measurements (but not angiographic imaging) and must make a decision based on conventional non-invasive ischemia detecting tests or clinical signs and symptoms i.e. very typical angina symptoms in patients with angiographic significant stenosis). randomised to guidelines group: Staged revascularisation by proven ischemia or persistence of symptoms of angina	FFR-guided Revascularisation Strategy n=295 Participants In the FFR-group all flow limiting (FFR≤0.80) lesions will receive treatment by PCI and stenting. The non-IRA PCI should be performed during the same intervention. Exceptions can be made for complex lesions where the operator estimates that the revascularisation procedure will require significant contrast overload which may lead to deterioration of cardiac and renal function of the patient. Such procedures can be performed in a second procedure which should take place within the same hospitalisation. All lesions with a FFR measurement of \>0.80 will not be treated. FFR-guided revascularisation strategy: FFR-guided revascularisation strategy
Number of Participants With Major Bleeding at 3 Year	8 Participants	3 Participants

SECONDARY outcome

Timeframe: 3 year

Number of participants with Hospitalization for heart failure, unstable angina, MI

Outcome measures

Measure	Randomised to Guidelines Group n=590 Participants In the randomised to guidelines group the procedure will stop after the FFR measurements and the patient will be referred to his treating cardiologist who will decide whether a staged PCI of the non-IRA artery should take place. The treating cardiologist will be blinded for the FFR measurements (but not angiographic imaging) and must make a decision based on conventional non-invasive ischemia detecting tests or clinical signs and symptoms i.e. very typical angina symptoms in patients with angiographic significant stenosis). randomised to guidelines group: Staged revascularisation by proven ischemia or persistence of symptoms of angina	FFR-guided Revascularisation Strategy n=295 Participants In the FFR-group all flow limiting (FFR≤0.80) lesions will receive treatment by PCI and stenting. The non-IRA PCI should be performed during the same intervention. Exceptions can be made for complex lesions where the operator estimates that the revascularisation procedure will require significant contrast overload which may lead to deterioration of cardiac and renal function of the patient. Such procedures can be performed in a second procedure which should take place within the same hospitalisation. All lesions with a FFR measurement of \>0.80 will not be treated. FFR-guided revascularisation strategy: FFR-guided revascularisation strategy
Number of Participants With Hospitalization	75 Participants	28 Participants

SECONDARY outcome

Timeframe: 3 year

Number of participants with Hospitalization for heart failure, unstable angina, MI and/or chest pain

Outcome measures

Measure	Randomised to Guidelines Group n=590 Participants In the randomised to guidelines group the procedure will stop after the FFR measurements and the patient will be referred to his treating cardiologist who will decide whether a staged PCI of the non-IRA artery should take place. The treating cardiologist will be blinded for the FFR measurements (but not angiographic imaging) and must make a decision based on conventional non-invasive ischemia detecting tests or clinical signs and symptoms i.e. very typical angina symptoms in patients with angiographic significant stenosis). randomised to guidelines group: Staged revascularisation by proven ischemia or persistence of symptoms of angina	FFR-guided Revascularisation Strategy n=295 Participants In the FFR-group all flow limiting (FFR≤0.80) lesions will receive treatment by PCI and stenting. The non-IRA PCI should be performed during the same intervention. Exceptions can be made for complex lesions where the operator estimates that the revascularisation procedure will require significant contrast overload which may lead to deterioration of cardiac and renal function of the patient. Such procedures can be performed in a second procedure which should take place within the same hospitalisation. All lesions with a FFR measurement of \>0.80 will not be treated. FFR-guided revascularisation strategy: FFR-guided revascularisation strategy
Number of Participants With Hospitalization at 3 Year	87 Participants	30 Participants

SECONDARY outcome

Timeframe: 3 year

Number of participants with Stent Thrombosis at 3 year - Part of composite endpoint NACE

Outcome measures

Measure	Randomised to Guidelines Group n=590 Participants In the randomised to guidelines group the procedure will stop after the FFR measurements and the patient will be referred to his treating cardiologist who will decide whether a staged PCI of the non-IRA artery should take place. The treating cardiologist will be blinded for the FFR measurements (but not angiographic imaging) and must make a decision based on conventional non-invasive ischemia detecting tests or clinical signs and symptoms i.e. very typical angina symptoms in patients with angiographic significant stenosis). randomised to guidelines group: Staged revascularisation by proven ischemia or persistence of symptoms of angina	FFR-guided Revascularisation Strategy n=295 Participants In the FFR-group all flow limiting (FFR≤0.80) lesions will receive treatment by PCI and stenting. The non-IRA PCI should be performed during the same intervention. Exceptions can be made for complex lesions where the operator estimates that the revascularisation procedure will require significant contrast overload which may lead to deterioration of cardiac and renal function of the patient. Such procedures can be performed in a second procedure which should take place within the same hospitalisation. All lesions with a FFR measurement of \>0.80 will not be treated. FFR-guided revascularisation strategy: FFR-guided revascularisation strategy
Number of Participants With Stent Thrombosis at 3 Year	12 Participants	4 Participants

SECONDARY outcome

Timeframe: 3 year

Number of participants with any bleeding at 3 year - Part of composite endpoint NACE

Outcome measures

Measure	Randomised to Guidelines Group n=590 Participants In the randomised to guidelines group the procedure will stop after the FFR measurements and the patient will be referred to his treating cardiologist who will decide whether a staged PCI of the non-IRA artery should take place. The treating cardiologist will be blinded for the FFR measurements (but not angiographic imaging) and must make a decision based on conventional non-invasive ischemia detecting tests or clinical signs and symptoms i.e. very typical angina symptoms in patients with angiographic significant stenosis). randomised to guidelines group: Staged revascularisation by proven ischemia or persistence of symptoms of angina	FFR-guided Revascularisation Strategy n=295 Participants In the FFR-group all flow limiting (FFR≤0.80) lesions will receive treatment by PCI and stenting. The non-IRA PCI should be performed during the same intervention. Exceptions can be made for complex lesions where the operator estimates that the revascularisation procedure will require significant contrast overload which may lead to deterioration of cardiac and renal function of the patient. Such procedures can be performed in a second procedure which should take place within the same hospitalisation. All lesions with a FFR measurement of \>0.80 will not be treated. FFR-guided revascularisation strategy: FFR-guided revascularisation strategy
Number of Participants With Any Bleeding at 3 Year	12 Participants	4 Participants

OTHER_PRE_SPECIFIED outcome

Timeframe: 3 year

FFR+/PCI+ vs FFR+/PCI- Comparison of patients having FFR positive lesions that underwent revascularization during index procedure or in staged procedures within 45 days (groups A+C, n=202 patients) with patients having FFR positive lesions that did not undergo revascularization (group D, n=231 patients),

Outcome measures

Measure	Randomised to Guidelines Group n=231 Participants In the randomised to guidelines group the procedure will stop after the FFR measurements and the patient will be referred to his treating cardiologist who will decide whether a staged PCI of the non-IRA artery should take place. The treating cardiologist will be blinded for the FFR measurements (but not angiographic imaging) and must make a decision based on conventional non-invasive ischemia detecting tests or clinical signs and symptoms i.e. very typical angina symptoms in patients with angiographic significant stenosis). randomised to guidelines group: Staged revascularisation by proven ischemia or persistence of symptoms of angina	FFR-guided Revascularisation Strategy n=202 Participants In the FFR-group all flow limiting (FFR≤0.80) lesions will receive treatment by PCI and stenting. The non-IRA PCI should be performed during the same intervention. Exceptions can be made for complex lesions where the operator estimates that the revascularisation procedure will require significant contrast overload which may lead to deterioration of cardiac and renal function of the patient. Such procedures can be performed in a second procedure which should take place within the same hospitalisation. All lesions with a FFR measurement of \>0.80 will not be treated. FFR-guided revascularisation strategy: FFR-guided revascularisation strategy
A Comparison of the Number of Patients in Both Groups With Treated Lesions With FFR ≤ 0.80 Versus Patients With Untreated Lesions With FFR ≤ 0.80;	90 Participants	35 Participants

OTHER_PRE_SPECIFIED outcome

Timeframe: 3 year

Comparison of acute versus staged PCI treatment for lesions with FFR

Outcome measures

Measure	Randomised to Guidelines Group n=44 Participants In the randomised to guidelines group the procedure will stop after the FFR measurements and the patient will be referred to his treating cardiologist who will decide whether a staged PCI of the non-IRA artery should take place. The treating cardiologist will be blinded for the FFR measurements (but not angiographic imaging) and must make a decision based on conventional non-invasive ischemia detecting tests or clinical signs and symptoms i.e. very typical angina symptoms in patients with angiographic significant stenosis). randomised to guidelines group: Staged revascularisation by proven ischemia or persistence of symptoms of angina	FFR-guided Revascularisation Strategy n=155 Participants In the FFR-group all flow limiting (FFR≤0.80) lesions will receive treatment by PCI and stenting. The non-IRA PCI should be performed during the same intervention. Exceptions can be made for complex lesions where the operator estimates that the revascularisation procedure will require significant contrast overload which may lead to deterioration of cardiac and renal function of the patient. Such procedures can be performed in a second procedure which should take place within the same hospitalisation. All lesions with a FFR measurement of \>0.80 will not be treated. FFR-guided revascularisation strategy: FFR-guided revascularisation strategy
Comparison of Acute Versus Staged PCI for Lesions With FFR ≤ 0.80	10 Participants	25 Participants

OTHER_PRE_SPECIFIED outcome

Timeframe: 3 year

comparison of patients receiving staged PCI treatment of FFR-negative lesions in the non-IRA (decision made by referring physician who was blinded to FFR results) and patients receiving medical therapy for FFR-negative lesions in the non-IRA

Outcome measures

Measure	Randomised to Guidelines Group n=418 Participants In the randomised to guidelines group the procedure will stop after the FFR measurements and the patient will be referred to his treating cardiologist who will decide whether a staged PCI of the non-IRA artery should take place. The treating cardiologist will be blinded for the FFR measurements (but not angiographic imaging) and must make a decision based on conventional non-invasive ischemia detecting tests or clinical signs and symptoms i.e. very typical angina symptoms in patients with angiographic significant stenosis). randomised to guidelines group: Staged revascularisation by proven ischemia or persistence of symptoms of angina	FFR-guided Revascularisation Strategy n=13 Participants In the FFR-group all flow limiting (FFR≤0.80) lesions will receive treatment by PCI and stenting. The non-IRA PCI should be performed during the same intervention. Exceptions can be made for complex lesions where the operator estimates that the revascularisation procedure will require significant contrast overload which may lead to deterioration of cardiac and renal function of the patient. Such procedures can be performed in a second procedure which should take place within the same hospitalisation. All lesions with a FFR measurement of \>0.80 will not be treated. FFR-guided revascularisation strategy: FFR-guided revascularisation strategy
Comparison of PCI vs Medical Therapy in FFR Negative Lesions	91 Participants	6 Participants

POST_HOC outcome

Timeframe: 3 year

post-hoc, per-protocol analysis, 328 underwent FFR-guided complete revascularization and 550 patients underwent IRA-only treatment, occurence of MACCE at 3 year

Outcome measures

Measure	Randomised to Guidelines Group n=550 Participants In the randomised to guidelines group the procedure will stop after the FFR measurements and the patient will be referred to his treating cardiologist who will decide whether a staged PCI of the non-IRA artery should take place. The treating cardiologist will be blinded for the FFR measurements (but not angiographic imaging) and must make a decision based on conventional non-invasive ischemia detecting tests or clinical signs and symptoms i.e. very typical angina symptoms in patients with angiographic significant stenosis). randomised to guidelines group: Staged revascularisation by proven ischemia or persistence of symptoms of angina	FFR-guided Revascularisation Strategy n=328 Participants In the FFR-group all flow limiting (FFR≤0.80) lesions will receive treatment by PCI and stenting. The non-IRA PCI should be performed during the same intervention. Exceptions can be made for complex lesions where the operator estimates that the revascularisation procedure will require significant contrast overload which may lead to deterioration of cardiac and renal function of the patient. Such procedures can be performed in a second procedure which should take place within the same hospitalisation. All lesions with a FFR measurement of \>0.80 will not be treated. FFR-guided revascularisation strategy: FFR-guided revascularisation strategy
Per Protocol Analysis - Occurence of MACCE at 3 Year	168 Participants	55 Participants

Adverse Events

FFR-guided Revascularisation Strategy

Serious events: 92 serious events

Other events: 12 other events

Deaths: 9 deaths

Randomised to Guidelines Group

Serious events: 308 serious events

Other events: 32 other events

Deaths: 21 deaths

Serious adverse events

Measure	FFR-guided Revascularisation Strategy n=295 participants at risk In the FFR-group all flow limiting (FFR≤0.80) lesions will receive treatment by PCI and stenting. The non-IRA PCI should be performed during the same intervention. Exceptions can be made for complex lesions where the operator estimates that the revascularisation procedure will require significant contrast overload which may lead to deterioration of cardiac and renal function of the patient. Such procedures can be performed in a second procedure which should take place within the same hospitalisation. All lesions with a FFR measurement of \>0.80 will not be treated. FFR-guided revascularisation strategy: FFR-guided revascularisation strategy	Randomised to Guidelines Group n=590 participants at risk In the randomised to guidelines group the procedure will stop after the FFR measurements and the patient will be referred to his treating cardiologist who will decide whether a staged PCI of the non-IRA artery should take place. The treating cardiologist will be blinded for the FFR measurements (but not angiographic imaging) and must make a decision based on conventional non-invasive ischemia detecting tests or clinical signs and symptoms i.e. very typical angina symptoms in patients with angiographic significant stenosis). randomised to guidelines group: Staged revascularisation by proven ischemia or persistence of symptoms of angina
Cardiac disorders Myocardial Infarction	6.8% 20/295 • Number of events 20 • 3 year	9.0% 53/590 • Number of events 53 • 3 year
Cardiac disorders PCI	11.5% 34/295 • Number of events 34 • 3 year	24.4% 144/590 • Number of events 144 • 3 year
Cardiac disorders Coronary Artery Bypass graft	1.0% 3/295 • Number of events 3 • 3 year	0.85% 5/590 • Number of events 5 • 3 year
Vascular disorders Cerebrovascular event	0.34% 1/295 • Number of events 1 • 3 year	1.2% 7/590 • Number of events 7 • 3 year
Cardiac disorders Stent Thrombosis	1.4% 4/295 • Number of events 4 • 3 year	2.0% 12/590 • Number of events 12 • 3 year
Cardiac disorders Cardiac Hospitalisations	10.2% 30/295 • Number of events 30 • 3 year	14.7% 87/590 • Number of events 87 • 3 year

Other adverse events

Measure	FFR-guided Revascularisation Strategy n=295 participants at risk In the FFR-group all flow limiting (FFR≤0.80) lesions will receive treatment by PCI and stenting. The non-IRA PCI should be performed during the same intervention. Exceptions can be made for complex lesions where the operator estimates that the revascularisation procedure will require significant contrast overload which may lead to deterioration of cardiac and renal function of the patient. Such procedures can be performed in a second procedure which should take place within the same hospitalisation. All lesions with a FFR measurement of \>0.80 will not be treated. FFR-guided revascularisation strategy: FFR-guided revascularisation strategy	Randomised to Guidelines Group n=590 participants at risk In the randomised to guidelines group the procedure will stop after the FFR measurements and the patient will be referred to his treating cardiologist who will decide whether a staged PCI of the non-IRA artery should take place. The treating cardiologist will be blinded for the FFR measurements (but not angiographic imaging) and must make a decision based on conventional non-invasive ischemia detecting tests or clinical signs and symptoms i.e. very typical angina symptoms in patients with angiographic significant stenosis). randomised to guidelines group: Staged revascularisation by proven ischemia or persistence of symptoms of angina
Blood and lymphatic system disorders any bleeding	4.1% 12/295 • Number of events 12 • 3 year	5.4% 32/590 • Number of events 32 • 3 year

Additional Information

Dr.Pieter Smits

Maasstad Hospital

Phone: +31102913322

Email: SmitsP@maasstadziekenhuis.nl

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place