Patients receiving the investigational anti-inflammatory drug losmapimod (GlaxoSmithKline) for 12 weeks after a heart attack did not show improvements in the trial’s primary endpoint, the rate of cardiovascular death, subsequent heart attack, or urgent coronary revascularization, which includes placement of a stent or coronary artery bypass surgery, according to research presented at the American College of Cardiology’s 65th Annual Scientific Session and published in the Journal of the American Medical Association.
The findings were from the initial phase of a study involving 3,500 patients. Because the trial failed to meet its primary endpoint, the authors said the second-phase study involving 22,000 patients will not go forward.
“Overall, the results were neutral, showing no evidence of efficacy in our primary analysis,” said lead author Michelle O'Donoghue, MD, a cardiologist at Brigham and Women's Hospital.
Although inflammation is a natural part of the body’s response to injury, in some cases it can cause more harm than good. Inflammation is thought to increase cardiovascular risk after a heart attack by affecting the healing of heart muscle tissue, increasing the formation of plaque in the arteries, and raising the likelihood that plaque will dislodge and cause another heart attack.
Losmapimod was developed to counteract these effects by inhibiting p38 mitogen-activated protein kinase, an enzyme in heart-muscle cells and other cell types that is activated by stressors, such as a heart attack, heart failure, or persistent hypertension. Earlier pilot studies involving several hundred patients suggested that losmapimod could reduce inflammation in patients undergoing stenting procedures and suggested that it might help protect against major adverse cardiovascular events.
The new trial, LATITUDE-TIMI 60, was a phase 3, randomized, double-blind study involving 3,500 patients hospitalized with an acute heart attack in 34 countries. Half of the patients received losmapimod 7.5 mg twice daily, and the other half received placebo.
After 12 weeks of treatment, a preliminary analysis showed no significant differences in the rates of cardiovascular death, subsequent heart attack, or urgent coronary revascularization in the patients receiving losmapimod compared with those receiving placebo. The primary endpoint was achieved by 12 weeks in 139 patients treated with losmapimod (8.1%) and in 123 patients treated with placebo (7.0%) (hazard ratio, 1.16; P = 0.24).
Although the study was not large enough to demonstrate effects in specific patient subgroups, O’Donoghue said further study of the cardiac effects of losmapimod may help to identify patients in whom the drug could be beneficial.