instantaneous wave-free ratio guided multi-vessel revascularization during percutaneous coronary intervention for acute myocardial infarction

In patients with acute ST-elevation myocardial infarction (STEMI), 40-60% have
multivessel disease, which is defined as 1 or more non-infarct lesions of >=50%.
The presence of multivessel disease is associated with an increased
cardiovascular morbidity and mortality. Recent investigations have shown
benefits of complete revascularization of residual coronary artery disease
during the primary percutaneous coronary intervention (pPCI). The control group
in these studies however consisted of patients in whom the residual coronary
artery disease was left untreated. This is not in accordance with contemporary
practice, in which non-infarct lesions are treated during a second
catheterization, preceded by non-invasive imaging (e.g.: cardiac MRI) in the
majority of cases.

Revascularization of functionally non-significant coronary lesions carries
unnecessary risk and may even worsen outcome. It is known that intervention
guided by intracoronary pressure measurements results in better outcome in
stable multivessel disease. The fractional flow reserve (FFR) and instantaneous
wave-free ratio (iFR) are both pressured derived indices used to assess
coronary lesion severity and guide revascularization. The reliability of these
indices during the acute phase of myocardial infarction however, has been
questioned. In our previous study (registration number: 2016.189) we
demonstrated that the iFR of non-infarct lesions measured during primary
intervention for STEMI is consistent with iFR measured 1 month afterwards.

The iMODERN trial will compare iFR-guided revascularization of noninfarct
lesions during acute intervention with a stress perfusion CMR-guided strategy
during the outpatient follow-up, to determine the optimal therapeutic approach
for STEMI patients with multi-vessel disease.

The study is a prospective, randomized controlled, open label multicenter
European trial.
Patients presenting with an acute STEMI will be screened for study enrollment
after succesfull intervention of the infarct lesion. Patients are eligible if
they are 18 years or older, have been revascularized within 12 hours of onset
of symptoms and have one or more noninfarct lesions of >=50%. Patients with
hemodynamic instability, Killips class >=II and patients who refuse or are
unable to provide informed consent will be excluded, as well as patients with a
history of myocardial infarction, a chronic total occlusion, complex
(bifurcation) lesions, a residual noninfarct lesion in the infarct coronary
artery or left main stenosis >=50%. Between patient admission and primary
intervention, the patient will be asked to participate in the study in case
multivessel disease is present. After successful intervention of the infarct
lesion the patient is told whether he or she is eligible for the study, and
will be asked again to participate in the trial. Upon verbal agreement,
randomization takes place. The subject information sheet (including the
informed consent form) will be provided to patients after return to the
coronary care unit. Hence on patients have 24 hours to decide whether they
still want to participate in the trial.

A total of 1146 patients will be randomized in a 1:1 fashion to either active
treatment or control. In the active treatment group, complete revascularization
of non-infarct coronary lesions >=50% and iFR<0.90 will be performed. Patients
randomized to control will undergo an adenosine stress perfusion CMR scan
within 6 weeks after STEMI, followed by revascularization of noninfarct
coronary lesion if associated perfusion defects are present. In case the
patient has contra-indications for CMR (sever claustrophobia, severe renal
failure, metal implants) or adenosine (e.g. astma), coronary angiography with
iFR measurements of noninfarct lesions will be used as bailout procedure.

The risks associated with participation are dependent on the randomized
treatment.

After acute intervention of the infarct lesion, patients randomized to the
intervention arm will undergo additional iFR measurements of all non-infarct
lesions >=50%, followed by stenting of the functionally significant lesions.
Intracoronary pressure measurements are routinely performed during
interventional procedures and are associated with a very small chance of wire
perforation (<0.1%).
Subsequent revascularization of significant non-infarct lesions also bears
risks, which are similar to regular PCI. Complications occur in 1% and include
coronary perforation, dissection and occlusion of side branches.

Patients randomized to the control group will undergo a stress CMR scan within
6 weeks after STEMI and if indicated additional stenting of significant
lesions. A CMR scan has marginal risks and is performed in about 45 minutes.