Atreleuton

Inflammation is emerging as an important risk factor for atherosclerotic cardiovascular disease and has been a recent target for many novel therapeutic agents. However, comparative evidence regarding efficacy of these anti-inflammatory treatment options is currently lacking.

This systematic review will include randomised controlled trials evaluating the effect of anti-inflammatory agents on cardiovascular outcomes in patients with known cardiovascular disease. Studies will be retrieved from Medline, Embase, the Cochrane Central Register of Controlled Trials, as well as clinical trial registry websites, Europe PMC and conference abstract handsearching. No publication date or language restrictions will be imposed. Eligible interventions must have some component of anti-inflammatory agent. These include (but are not limited to): non-steroidal anti-inflammatory drugs (NSAIDs), colchicine, prednisone, methotrexate, canakinumab, pexelizumab, anakinra, succinobucol, losmapimod, inclacumab, atreleuton, LP-PLA 2 (darapladib) and sPLA 2 (varespladib). The primary outcomes will include major adverse cardiac events (MACE), and each individual component of MACE (myocardial infarction, stroke and cardiovascular death). Key secondary outcomes will include unstable angina, heart failure, all-cause mortality, cardiac arrest and revascularisation. Screening, inclusion, data extraction and quality assessment will be performed independently by two reviewers. Network meta-analysis based on the random effects model will be conducted to compare treatment effects both directly and indirectly. The quality of the evidence will be assessed with appropriate tools including the Grading of Recommendations, Assessment, Development and Evaluation profiler or Confidence in Network Meta-Analysis tool.

Ethics approval is not required for this systematic review. The findings will be disseminated through a peer-reviewed journal.

CRD42022303289.

Inhibition of multiple enzymes of the arachidonic acid cascade leads to synergistic anti-inflammatory effects. Merging of 5-lipoxygenase (5-LOX) and soluble epoxide hydrolase (sEH) pharmacophores led to the discovery of a dual 5-LOX/sEH inhibitor, which was subsequently optimized in terms of potency toward both targets and metabolic stability. The optimized lead structure displayed cellular activity in human polymorphonuclear leukocytes, oral bioavailability, and target engagement in vivo and demonstrated profound anti-inflammatory and anti-fibrotic efficiency in a kidney injury model caused by unilateral ureteral obstruction in mice. These results pave the way for investigating the therapeutic potential of dual 5-LOX/sEH inhibitors in other inflammation- and fibrosis-related disease models.