The p38 mitogen-activated protein kinase (MAPK)-stimulated inflammation is implicated in atherogenesis, plaque destabilization, and maladaptive processes in myocardial infarction (MI). Pilot data in a phase 2 trial in non-ST elevation MI indicated that the p38 MAPK inhibitor losmapimod attenuates inflammation and may improve outcomes.
Objective of this paper was to evaluate the efficacy and safety of losmapimod on cardiovascular outcomes in patients hospitalized with an acute myocardial infarction. After randomization to either twice-daily losmapimod (7.5 mg; n = 1738) or matching placebo (n = 1765), the Authors observed that use of losmapimod compared with placebo did not reduce the risk of major ischemic cardiovascular events among patients with acute MI. According to Author's conclusions, the results of this exploratory efficacy study did not justify proceeding to a larger efficacy trial in the existing patient population.
- O'Donoghue ML, Glaser R, Cavender MA, Aylward PE, Bonaca MP, Budaj A, Davies RY, Dellborg M, Fox KA, Gutierrez JA, Hamm C, Kiss RG, Kovar F, Kuder JF, Im KA, Lepore JJ, Lopez-Sendon JL, Ophuis TO, Parkhomenko A, Shannon JB, Spinar J, Tanguay JF, Ruda M, Steg PG, Theroux P, Wiviott SD, Laws I, Sabatine MS, Morrow DA; LATITUDE-TIMI 60 Investigators. Salvioni A in appendice. Effect of Losmapimod on Cardiovascular Outcomes in Patients Hospitalized With Acute Myocardial Infarction: A Randomized Clinical Trial. JAMA 16;315(15):1591-9. Go to PubMed