Pexelizumab

Reperfusion serves as a mainstay therapy in almost all ischemic vascular diseases (IVD), but reperfusion may enhance cell damage after an ischemic period time. Increased ROS and inflammatory markers, decreasing organ function parameters, along with systemic inflammatory response and multi-organ damage may occur in ischemic reperfusion injury (IRI). Unfortunately, this series of events is unpredictable and sudden, causing high mortality in patients with IRI. Due to the significant role of inflammation in IRI, how is the effectiveness of anti-inflammatory agents administered before reperfusion therapy to prevent IRI? To know the efficacy of anti-inflammatory agents administered before reperfusion therapy to prevent IRI.

A systematic search was conducted in databases (Pubmed, EMBASE, Scopus) and was later selected according to predetermined inclusion and exclusion criteria. Studies included later critically appraised using the CEBM Oxford questionnaire for randomized control trials and systematic review.

Seven studies were included among 1072 studies found in early searching. Six of the studies are randomized control trials, and one is a meta-analysis of randomized control trials. Methylprednisolone, pexelizumab, tirilazad mesylate, and N-acetylcysteine are known anti-inflammatory agents applicable in humans. The highest effectiveness of anti-inflammatory agents is methylprednisolone, with a relative risk reduction (RRR) of 75-85%. Besides that, pexelizumab also had an RRR of 27%, and tirilazad-mesylate had an RRR of 18%. N-acetylcysteine is not effective in preventing IRI. IL-6 levels postoperatively also decreased significantly in patients given anti-inflammatory agents before reperfusion therapy. There are no side effects of the intervention reported.

Anti-inflammatory agent administration before reperfusion therapy effectively prevents IRI. The choices of anti-inflammatory agents recommended are methylprednisolone, pexelizumab, and tirilazad-mesylate. Anti-inflammatory agent administration before reperfusion therapy is recommended.

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.