The Effect of Zalunfiban on High Sensitivity Cardiac Troponin and the Association with Clinical Outcomes in Patients with STEMI.
BACKGROUND: Among patients with ST segment elevation myocardial infarction (STEMI), higher concentrations of high sensitivity troponin T (hs-cTnT) are associated with larger MI size and predict a worse prognosis. In the 2467 patient CELEBRATE trial, 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. In this study, we assessed 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: The median concentration of hs-cTnT at presentation was 62 ng/L; at 24 hours it was 1962 ng/L. More elevated hs-cTnT concentrations at presentation were associated with less resolution of ST deviation after revascularization (P =0.006) and more frequent Q wave development (all P <0.001). At coronary angiography more elevated hs-cTnT at presentation was also 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 (or cardiovascular death) and heart failure (P<0.001) by 30 days. At 24 hours, those treated with zalunfiban had lower hs-cTnT compared to placebo (1900 vs 2082 ng/L; 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, higher concentrations of hs-cTnT are associated with worse angiographic and ECG measures of reperfusion. More elevated hs-cTnT predicted a higher risk for short-term death or heart failure. A single dose of zalunfiban at first medical contact reduced MI size, as judged by more study participants with lower hs-cTnT concentrations. These results provide a mechanistic basis for the improved clinical outcomes associated with zalunfiban treatment in the CELEBRATE Trial. STUDY REGISTRATION: A Phase 3 Study of Zalunfiban in Subjects With ST-elevation MI (CELEBRATE); NCT04825743.
