A Pairwise and Network Meta-analysis of Anti-inflammatory Strategies After Myocardial Infarction: the TITIAN study

Abstract Background and aims Multiple anti-inflammatory drugs have been tested for secondary prevention after myocardial infarction (MI), giving mixed results and questioning the efficacy of anti-inflammatory therapy. No head-to-head comparisons between anti-inflammatory drugs have been performed. This study aimed to compare the efficacy and safety of anti-inflammatory drugs for secondary prevention after MI and the relative merits of specific drugs and administration strategies. Methods Randomized trials of anti-inflammatory therapy for secondary prevention after MI were identified. Primary efficacy and safety endpoints were trial-defined major adverse cardiovascular events (MACE) and serious adverse events. Secondary endpoints included all-cause death, individual MACE components, serious infection, cancer, and gastrointestinal adverse events. Pairwise meta-analyses were conducted with interaction analyses for drug type and timing of administration, in addition to network meta-analyses. Multiple sensitivity and meta-regression analyses were conducted to explore potential heterogeneity sources. Results Twenty-eight studies, involving 44 406 patients with a mean follow-up of 11 months, were included. Anti-inflammatory therapy reduced the incidence of major adverse cardiovascular events (MACE) (incidence rate ratio [IRR]: 0.92; 95% confidence interval [CI]: 0.86–0.98), without increasing serious adverse events. However, it was associated with a higher incidence of gastrointestinal adverse events (IRR: 1.21; 95% CI: 1.07–1.36). No significant interaction was observed between the effects of anti-inflammatory therapy on MACE and the timing of administration. Conclusions In secondary prevention for MI, anti-inflammatory therapy significantly reduces MACE without increasing serious adverse events, but it is associated with an increased risk of gastrointestinal adverse events.