Inhibition of p38 MAP Kinase in Patients with ST-Elevation Myocardial Infarction - Findings from the LATITUDE TIMI 60 Trial.

Abstract Background p38 mitogen activated kinase (MAPK) mediates the response to pro-inflammatory cytokines following myocardial infarction (MI) and is inhibited by losmapimod. Methods LATITUDE-TIMI 60 (ClinicalTrials.gov NCT02145468) randomized patients with MI to losmapimod or placebo for 12 weeks (24 weeks total follow-up). In this pre-specified analysis, we examined outcomes based on MI type [ST-segment elevation MI (STEMI) (865, 25%) and non-STEMI (2624, 75%)]. Results In patients with STEMI, inflammation, measured by hs-CRP, was significantly attenuated with losmapimod at 48 hours (p Conclusions Patients with STEMI treated with losmapimod had an attenuated inflammatory response. Our collective findings raise the hypothesis that mitigating the inflammatory response may result in different outcomes in patients with STEMI and NSTEMI. While the difference in outcomes is exploratory, these findings do support separate examination of patients with STEMI and NSTEMI and increased emphasis on heart failure in future investigation of modulators of inflammation in MI.