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

Fang He; Tian Xie; Dong Ni; Tingting Tang; Xiang Cheng

doi:10.1111/eci.14062

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

Eur J Clin Invest. 2023 Nov;53(11):e14062. doi: 10.1111/eci.14062. Epub 2023 Jul 10.

Authors

Fang He^{1

2

3}, Tian Xie^{1

2

3}, Dong Ni⁴, Tingting Tang^{1

2

3}, Xiang Cheng^{1

2

3}

Affiliations

¹ Department of Cardiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
² Hubei Key Laboratory of Biological Targeted Therapy, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
³ Hubei Provincial Engineering Research Center of Immunological Diagnosis and Therapy for Cardiovascular Diseases, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
⁴ Department of Urology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

PMID: 37427709
DOI: 10.1111/eci.14062

Abstract

Background: The 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.

Methods: This 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.

Results: Of 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.

Conclusions: There 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.

Keywords: NLRP3; STEMI; anakinra; colchicine; interleukin; meta-analysis; tocilizumab.

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Abstract

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