The Effect of Zalunfiban on High Sensitivity Cardiac Troponin and the Association with Clinical Outcomes in Patients with STEMI

BACKGROUND: Among individuals with ST-segment elevation myocardial infarction (STEMI), a single subcutaneous injection of the short-acting glycoprotein IIb/IIIa receptor blocker antagonist zalunfiban at first medical contact significantly improved the primary outcome including clinical endpoints. The impact of zalunfiban on MI size and association with downstream outcomes remains unclear. METHODS: In a prespecified analysis, we studied results among study participants treated with two doses of zalunfiban who had core laboratory measurements concentrations of hs-cTnT. RESULTS: More elevated hs-cTnT concentrations at presentation were associated with less resolution of ST deviation (P =0.006) and more frequent Q wave development (P <0.001). At coronary angiography more elevated hs-cTnT at presentation was associated with higher thrombus grade and worse epicardial and myocardial perfusion (all P <0.05). In multivariable analyses, higher hs-cTnT concentrations at 24 hours were associated with greater adjusted risk for all-cause death (odds ratio OR 1.83 per log unit increase; P=0.03), cardiovascular death (OR 1.83 per log unit increase; P=0.03), heart failure (OR 2.74 per log unit increase; P <0.001) or the composite of death and heart failure (P<0.001) by 30 days. At 24 hours, those treated with zalunfiban had lower hs-cTnT compared to placebo (P =0.04) and across multiples ≥10 to ≥1000 times elevation, treatment with zalunfiban resulted in smaller hs-cTnT determined MI size. CONCLUSION: Among patients with STEMI, more elevated concentrations of hs-cTnT are associated with worse measures of reperfusion and higher risk for short-term death or heart failure. A single dose of zalunfiban at first medical contact reduced MI size. STUDY REGISTRATION: A Phase 3 Study of Zalunfiban in Subjects With ST-elevation MI (CELEBRATE); NCT04825743.