Efficacy of interleukin-1 blockade for prevention of heart failure outcomes in patients with prior myocardial Infarction: a systematic review and meta-analysis of 10301 patients
N B Tran, V Q T Ho, N Nguyen, V N D NguyenAbstract
Background
Inflammation is a vital mechanism in left ventricular remodeling and contributes to heart failure following myocardial infarction (MI) 1. Interleukin-1 (IL-1) is a key pro-inflammatory cytokine found in post-MI ventricular dysfunction and heart failure development. Although IL-1 blockade has shown anti-inflammatory and cardioprotective effects in early clinical studies, its impact on clinically significant heart failure outcomes in patients with prior MI remains uncertain.
Purpose
To systematically evaluate the efficacy of interleukin-1 blockade compared with placebo on heart failure hospitalization (HHF), all-cause mortality, and the composite of HHF or all-cause mortality in patients with prior myocardial infarction.
Methods
A systematic review and meta-analysis was conducted in accordance with PRISMA guidelines. PubMed, Embase, and the Cochrane Library were searched from inception without time restriction. Randomized controlled trials (RCTs) enrolling adult patients with prior MI and comparing IL-1 blockade with placebo were eligible. Outcomes of interest were HHF, all-cause mortality and the composite outcome of HHF or all-cause mortality. Pooled risk ratios (RR) with 95% confidence intervals (CI) were calculated using a random-effects model. Statistical heterogeneity was assessed using the I² statistic.
Results
A total of five RCTs comprising 10301 patients with prior myocardial infarction were included. Three IL-1 inhibitors were evaluated: canakinumab, anakinra, and goflikicept. The mean age was 61 and 61.03 years in the IL-1 inhibitors group and placebo group, respectively. Males comprised 74.3% of both groups. Follow-up time ranges from one to five years. In the pooled analysis, Interleukin-1 blockade was not associated with a statistically significant reduction in the composite outcome of HHF or all-cause mortality compared with placebo (RR=0.91; 95% CI 0.82-1.01; I²=0%; p=0.07). Similarly, no statistically significant reduction was observed for HHF alone (RR=0.88; 95% CI 0.72-1.08; I²=0%; p=0.22) or for all-cause mortality (RR=0.27; 95% CI 0.04-2.00; I² = 0%; p=0.2). Subgroup analyses according to individual IL-1 inhibitors (canakinumab, anakinra, and goflikicept) demonstrated a consistent direction of effect without significant subgroup heterogeneity.
Conclusions
Among patients with prior myocardial infarction, interleukin-1 blockade did not significantly reduce heart failure hospitalization, the composite of heart failure hospitalization or all-cause mortality, or all-cause mortality compared with placebo. While point estimates suggest a possible benefit, existing trial data are insufficient, and larger trials targeting post-MI patients are required to clarify the therapeutic role of IL-1 inhibition in heart failure prevention.Forest plots - Heart failure outcomesFor image description, please refer to the figure legend and surrounding text.