Key result
Anti-inflammatory therapies fail to reduce MACE but cut MI risk ~15%.
Why the study?
Treatment effects of anti-inflammatory therapies inhibiting the NLRP3/IL-1β/IL-6/CRP pathway in coronary artery disease have shown conflicting results.
Do anti-inflammatory therapies inhibiting the NLRP3/IL-1β/IL-6/CRP pathway reduce major adverse cardiovascular events in patients with coronary artery disease?
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.
Does not support MACE prevention in CAD; challenges broad pathway inhibition while leaving targeted MI benefits open.
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.
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Pan et al. (2025) 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%.
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