Persistent residual inflammatory risk at 1 month after contemporary PCI: rationale for routine hsCRP reassessment and dual-target therapy

Despite major advances in lipid-lowering therapy and stent technology, a substantial proportion of patients undergoing contemporary percutaneous coronary intervention (PCI) experience recurrent major adverse cardiovascular events (MACE) driven by persistent residual inflammatory risk (RIR). This Perspective highlights that, once LDL−C is optimized below 70 mg/dL, RIR—quantified by high−sensitivity C−reactive protein (hsCRP ≥2 mg/L)—emerges as the dominant modifiable driver of recurrent events. Landmark meta−analyses and large registries demonstrate that persistent elevation of hsCRP at 1 month post−PCI occurs in approximately 43% of patients and independently predicts 12−month MACE (RR 1.64), all−cause mortality (RR 3.25), and other adverse outcomes, outperforming residual cholesterol risk after multivariable adjustment. Mechanistically, the acute−phase hsCRP surge induced by procedural injury resolves by 4–6 weeks, after which the 1−month value reliably reflects ongoing NLRP3 inflammasome activation, IL−1β/IL−6 signaling, and macrophage−driven plaque inflammation rather than transient artefacts. Accordingly, we propose a new “dual−target” definition of optimal secondary prevention: achievement of both LDL−C <70 mg/dL and hsCRP <2 mg/L at the 1−month landmark. This biomarker−guided approach represents a hypothesis-generating framework to enable precision deployment of low−dose colchicine or IL−6 pathway inhibitors (e.g., ziltivekimab) in patients with persistent RIR, directly addressing the enrichment gap observed in neutral broad anti−inflammatory trials such as CLEAR−SYNERGY. We therefore propose consideration of routine 1−month hsCRP reassessment as a potential future Class IIa recommendation in ESC/ACC guidelines. This strategy may transform silent residual inflammatory risk into a precisely treatable immunologic target, pending prospective validation in dedicated trials.