Residual inflammatory risk and clinical outcomes after contemporary percutaneous coronary intervention: a systematic review and meta-analysis

Elevated low-density lipoprotein cholesterol (LDL-C) and subclinical inflammation - measured with high-sensitivity C-reactive protein (hsCRP) - contribute to atherosclerosis progression. Despite medical therapy, high-risk patients may still have residual cholesterol risk, residual inflammatory risk (RIR), both, or neither. We aimed to study the impact of RIR in patients undergoing contemporary percutaneous coronary intervention (PCI). A comprehensive search of Pubmed, EMBASE, Cochrane and MEDLINE was performed up to December 2024. Only studies including patients with coronary artery disease undergoing PCI were considered. Inflammatory burden was evaluated with two hs-CRP measurements at baseline and follow-up (> 4 weeks apart). High RIR was defined as hsCRP ≥ 2 mg/L at 1-month follow-up. The risk ratio (RR) with a 95% confidence interval (CI) was computed using a random-effect model. We identified five studies enrolling 13,604 patients, including 5,833 with high RIR at 30 days post-PCI. At 12-month follow-up, persistent high RIR was associated with an increased risk of major adverse cardiovascular events (MACE) (random-effects RR = 1.64, 95% CI 1.33-2.03; I² = 80.2%). High RIR was also associated with increased all-cause mortality (random-effects RR = 3.25, 95% CI 2.49-4.25; I² = 67%), non-fatal myocardial infarction (random-effects RR = 1.46, 95% CI 1.00-2.12; I² = 73%), and non-fatal stroke (random-effects RR = 1.64, 95% CI 1.14-2.37; I² = 0%). Sensitivity analyses, including Baujat plots and leave-one-out analyses, identified a single study as a major contributor to heterogeneity; exclusion of this study substantially reduced heterogeneity without materially altering the direction or magnitude of the associations. In patients undergoing contemporary PCI, a high RIR was associated with a significantly higher risk of adverse cardiovascular outcomes. This data could help tailor lipid-lowering and anti-inflammatory therapies in this high-risk population.