Inhibition of late sodium current (INa) to prevent coronary MICROvascular dysfunction in patients presenting with ST-elevation myocardial infarction and multivessel disease: A phase IIb multicenter, randomized, controlled and open label study (INaMICRON)

INTRODUCTION: Residual coronary microvascular dysfunction (CMD) is common after STEMI despite successful primary PCI and may contribute to ongoing ischemia and impaired recovery. INaMICRON will test the hypothesis that early late INa current inhibition with ranolazine, added to guideline-directed medical therapy, favorably modulates microvascular function during the early post-infarction phase. METHODS AND RESULTS: INaMICRON is a prospective, multicenter, randomized (1:1), open-label phase IIb trial enrolling adults with STEMI treated with successful primary PCI and at least one significant non-culprit lesion suitable for staged PCI. Participants will be randomized to standard therapy plus ranolazine (500 mg bid for 7 days, then 750 mg bid up to 42 ± 7 days) or standard therapy alone. Coronary microvascular function will be assessed using IMR and/or angioIMR in the culprit vessel after primary PCI (baseline) and during staged PCI (follow-up); non-culprit vessel physiology will also be assessed during the staged procedure. Complementary evaluations include peripheral endothelial function testing (EndoPAT), a single CMR at 42 ± 7 days, and paired blood sampling for translational multi-omics analyses. The planned sample size is 100 patients (50 per group), and analyses will compare between-group differences in physiology and related measures and explore predefined correlations. The study is designed to estimate the magnitude of microvascular modulation in the experimental group. CONCLUSIONS: This trial will provide feasibility data and an estimate of the magnitude of microvascular modulation achievable with early ranolazine after STEMI, informing the design of larger outcome-oriented studies and future precision approaches to post-MI care.