Anti-inflammatory therapies inhibiting the NLRP3/IL-1β/IL-6/CRP pathway did not significantly reduce MACE (RR 0.83) but reduced myocardial infarction by 15% and coronary revascularization by 20%.
Meta-Analysis (n=37,056)
Do anti-inflammatory therapies inhibiting the NLRP3/IL-1β/IL-6/CRP pathway reduce major adverse cardiovascular events in patients with coronary artery disease?
Anti-inflammatory therapies targeting the NLRP3/IL-1β/IL-6/CRP pathway safely reduce the risk of myocardial infarction and coronary revascularization in CAD patients, though they do not significantly reduce MACE or mortality.
Effect estimate: RR 0.83 (95% CI 0.67-1.02)
BACKGROUND: Treatment effects of anti-inflammatory therapies inhibiting the NLRP3/IL-1β/IL-6/CRP pathway in coronary artery disease (CAD) had conflicting results. The study aims to evaluate efficacy and safety outcomes of treatments inhibiting this pathway. METHODS: Cochrane Library, Embase, Pubmed, and ClinicalTrials.gov were searched for randomized controlled trials evaluating therapies inhibiting the NLRP3/IL-1β/IL-6/CRP pathway in CAD patients. Relative risks (RR) with 95% confidence intervals (CI) were calculated. RESULTS: 32 studies and 37,056 individuals were included. Anti-inflammatory therapies inhibiting the pathway reduced the risks of myocardial infarction (MI) (RR 0.85, 95% CI 0.78-0.93) and coronary revascularization (RR 0.80, 95% CI 0.74-0.86), with no benefits in major adverse cardiovascular events (MACE), heart failure (HF), stroke, cardiovascular or all-cause mortality. Colchicine reduced the risks of MACE, MI, and coronary revascularization. IL-1 inhibitors reduced the risks of coronary revascularization, with potential benefits in MI and HF. Increased risks of infections, gastrointestinal adverse effects, and injection site reactions were found. Meta-regression analysis demonstrated that post-treatment hsCRP/CRP was correlated with MACE (p < 0.001) and MI (p = 0.048) and post-treatment IL-6 was associated with MI (p = 0.033). CONCLUSION: Anti-inflammatory therapies inhibiting the NLRP3/IL-1β/IL-6/CRP pathway had satisfying safety profiles and were beneficial in preventing MI and coronary revascularization in CAD patients despite no benefits in stroke, cardiovascular, or all-cause mortality.
Pan et al. (Sun,) conducted a meta-analysis in Coronary artery disease (n=37,056). Anti-inflammatory therapies inhibiting the NLRP3/IL-1β/IL-6/CRP pathway vs. Placebo or no anti-inflammatory therapies was evaluated on Major adverse cardiovascular events (MACE) (RR 0.83, 95% CI 0.67-1.02). Anti-inflammatory therapies inhibiting the NLRP3/IL-1β/IL-6/CRP pathway did not significantly reduce MACE (RR 0.83) but reduced myocardial infarction by 15% and coronary revascularization by 20%.