Efficacy and safety of inhibiting the NLRP3/IL‐1β/IL‐6 pathway in patients with ST‐elevation myocardial infarction: A meta‐analysis

Abstract

AbstractBackgroundThe NLRP3/IL‐1β/IL‐6 pathway plays a key role in mediating inflammatory responses after ST‐elevation myocardial infarction (STEMI). However, the clinical benefits of inhibiting this pathway in STEMI are uncertain. We aimed to evaluate the efficacy and safety of inhibiting the NLRP3/IL‐1β/IL‐6 pathway in STEMI patients.MethodsThis study followed PRISMA guidelines. PubMed, Embase, CENTRAL and ClinicalTrials.gov databases were searched for randomized controlled trials (RCTs) of inhibiting the NLRP3/IL‐1β/IL‐6 pathway in STEMI patients within 7 days of symptom onset. The efficacy outcomes included all‐cause death, cardiovascular death, recurrent MI, new‐onset or worsening heart failure (HF) and stroke. The safety outcomes were serious infection, gastrointestinal adverse events and injection site reactions.ResultsOf 316 screened records, nine trials with 1211 patients were included in the meta‐analysis. Colchicine reduced the risk of recurrent MI (RR 0.28, 95% CI 0.10–0.74; I2 = 0.0%). Anakinra was associated with reduced risk of new‐onset or worsening HF (RR 0.32, 95% CI 0.13–0.77; I2 = 0.0%) and decreased C‐reactive protein levels (SMD −1.34, 95% CI −2.04 to −0.65; I2 = 0.0%). Colchicine and anakinra increased the risk of gastrointestinal adverse events (RR 4.43, 95% CI 2.75–7.13; I2 = 38.1%) and injection site reactions (RR 4.52, 95% CI 1.32–15.49; I2 = 0.8%), respectively. None of the three medications affected the risks of all‐cause death, cardiovascular death, stroke and serious infection.ConclusionsThere is still no large‐scale RCT evidence on the efficacy and safety of inhibiting the NLRP3/IL‐1β/IL‐6 pathway for the treatment of STEMI. Preliminary results from the available RCTs suggest colchicine and anakinra may respectively reduce the risks of recurrent MI and new‐onset or worsening HF. The available RCTs in this meta‐analysis lack power to determine any differences on mortality.