Maladaptive processes after myocardial infarction (MI) might involve p38 mitogen-activated protein kinase (MAPK)-stimulated inflammation. However, in the LATITUDE-TIMI 60 trial, treatment with losmapimod to inhibit p38 MAPK in patients with acute MI did not reduce the risk of major ischaemic cardiovascular events compared with placebo. A total of 3,503 patients were randomly assigned to losmapimod (7.5 mg orally twice daily) or placebo. The primary end point (a composite of cardiovascular death, MI, or severe recurrent ischaemia requiring urgent coronary revascularization) occurred in 8.1% and 7.0% of patients in each group, respectively, during the 12-week follow-up (HR 1.16, 95% CI 0.91–1.47). On the basis of these exploratory findings, the investigators did not proceed to a larger efficacy trial that had been planned.
References
O'Donoghue, M. L. et al. Effect of losmapimod on cardiovascular outcomes in patients hospitalized with acute myocardial infarction: a randomized clinical trial. JAMA http://dx.doi.org/10.1001/jama.2016.3609 (2016)
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Lim, G. Anti-inflammatory therapy after acute MI. Nat Rev Cardiol 13, 312 (2016). https://doi.org/10.1038/nrcardio.2016.65
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DOI: https://doi.org/10.1038/nrcardio.2016.65