P3427Intra-coronary administration of tacrolimus improves myocardial perfusion and LV function in patients with ST-segment elevation myocardial infarction undergoing primary coronary intervention

Abstract

Background: Effective therapeutics for reperfusion injury or no-reflow phenomenon during primary percutaneous intervention (PCI) for ST-elevation myocardial infarction (STEMI) remains lacking. We intended to investigate whether intracoronary (IC) injection of tacrolimus could improve myocardial perfusion status and clinical outcomes. Methods: A multicenter double-blind randomized controlled trial (COAT-STEMI) was conducted since 2014 through 2017. We assigned 335 STEMI patients undergoing primary PCI into study group (IC tacrolimus 2.5 mg to culprit vessel before first balloon inflation) and placebo group (IC saline only) in a 1:1 ratio. Those patients with initial prevention of Killip III and IV STEMI were excluded from this study. The primary endpoints were defined as 1-month and 1-year major adverse cardiac events (MACE), including death, MI, stroke, repeated revascularization and hospitalization for heart failure. The secondary endpoints included angiographic TIMI myocardial perfusion grade (TMP), ST segment resolution (STR) on 90-minute follow-up electrocardiography, and echocardiographic left ventricular (LV) function. Results: There was no significant difference in baseline characteristics between 154 patients in the tacrolimus group and 165 in the placebo group. The rate of MACE at 1 month (3.7% vs. 4.8%, P=0.634) and 1 year (11.8% vs. 11.4%, P=0.905) were similar between the two groups. In terms of perfusion status, post-PCI TMP grade (2.52 vs. 2.25, P=0.001), achievement of TMP grade 2 or 3 (92.6% vs. 84.7%, P=0.023) and 90-minute STR (65% vs. 51%, P<0.001) were significantly higher in the tacrolimus than placebo group. Additionally, the tacrolimus group had also higher 3D LV ejection fraction (60.7% vs. 57.8%, P=0.046) and lower mitral E/A ratio (0.47 vs. 0.67, P=0.014) at 9 months than the placebo group. Conclusion: Intracoronary tacrolimus therapy for STEMI demonstrates the beneficial effects on the improvement of myocardial perfusion status and 9-month LV systolic and diastolic function, but not in clinical outcomes.