This is a Phase IIb, multicentric, prospective, randomized (1:1 ratio), open label, and no profit study, with the aim of evaluating the efficacy of late INa current inhibition to improve coronary microcirculation in patients presenting with acute myocardial infarction and multivessel disease.
All consecutive patients presenting with acute MI undergoing primary PCI (pPCI) on a major coronary artery, and with at least one remaining angiographically significant (% diameter stenosis \> 50%) non-culprit stenosis will be enrolled.
The primary objective of the study is to evaluate the potential effect of Ranolazine in preserving coronary microcirculation subtended to the culprit vessel as compared with control group. Coronary microcirculation will be assessed both at the time of the culprit lesion revascularization and within 6+/-2 weeks by measuring the Index of Microcirculatory Resistance (IMR) either invasively or derived by the angiography (angioIMR).
In addition, the following secondary endpoints will be assessed: 1. The prevalence of residual CMD downstream to the culprit vessel in all patients (CMDculprit). CMDculprit will be defined as the finding of an IMR/angioIMR value \> 25, assessed after successful pPCI.
2\. The prevalence of CMD downstream to the non-culprit vessel in the two group of patients (CMDnon-culprit). CMDnon-culprit will be defined as the finding of an IMRnon-culprit or an angioIMRnon-culprit value \> 25. IMRnon-culprit or angioIMRnon-culprit will be assessed at the time of staged PCI of the non-culprit stenosis.
3\. The incidence of peri-procedural CMD after staged PCI of the non-culprit stenoses, defined as a 20% increase of IMR values assessed before and after elective PCI of the non-culprit vessel (CMDprocedural).
4\. The difference between the two groups of patients, in terms of incidence of periprocedural Myocardial Infarction (PMI), eventually occurring during the staged procedure.
5\. The effects of INa current inhibition on endothelial function assessed at follow up as compared with control group.
6\. The extent of the Infarct Size, as assessed by the CMR, as compared with control group.
7\. The incidence of MACE, defined as composite of death, myocardial infarction, periprocedural MI, or any unplanned percutaneous coronary revascularization at short (42+/-7 days) term follow-up.
8\. Angina symptoms and quality of life
Age ≥ 18 years and < 80 years on day of signing informed consent
Ability to provide written informed consent in a time window 0 to 1 day after successful pPCI
ST-Elevation Myocardial Infarction at the time of the index hospitalization.
Successful pPCI (Thrombolysis In Myocardial Infarction [TIMI] flow 3 and residual coronary stenosis <30%)
Hemodynamically unstable patients
Previous myocardial infarction
Previous coronary artery by-pass graft (CABG)
Female patients with a positive pregnancy test at enrollment or prior to administration of study medication.
Parallel
Ranolazine
DrugPatients enrolled in the experimental group will receive ranolazine by oral administration, on top of regular therapy, starting with a dosage of 500mg bid and increased at 750mg bid starting from 7 days after pPCI up to 6 +/-2 weeks.
Preservation of the coronary microcirculation
he relative difference in terms of IMR and/or angioIMR will be evaluated. IMR and/or angioIMR will be assessed both at the baseline (after successful coronary revascularization) and at the time of staged revascularization of the non-culprit stenosis (either at 5+/-2 days or within 6+/-2 weeks after pPCI).
Difference in terms of CMD prevalence between the two groups
The prevalence of residual CMD downstream to the culprit vessel in the two group of patients. Residual CMD will be defined as the finding of an IMRculprit or angioIMRculprit value \> 25
Infarct Size Extension
The extent of the Infarct Size, as assessed by the CMR, in terms of grams (g) and percentage as compared with control group
CMD prevalence downstream to the non-culprit vessel before staged PCI
The prevalence of CMD downstream to the non-culprit vessel in the two group of patients (CMDnon-culprit). CMDnon-culprit will be defined as the finding of an IMRnon-culprit or angioIMRnon-culprit value \> 25
CMD prevalence after staged PCI
The incidence of peri-procedural CMD after staged PCI of the non-culprit stenoses, defined as a 20% increase of IMRnon-culprit or angioIMRnon-culprit values assessed before and after elective PCI of the non-culprit vessel.
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Federico II University
Lead sponsor
Università Magna Grecia, Catanzaro
Collaborator
Santa Maria Goretti Hospital, Latina
Collaborator
