Low-dose colchicine has re-emerged as a pragmatic anti-inflammatory strategy to address residual atherothrombotic risk in coronary artery disease, with randomized evidence showing fewer recurrent ischemic events when therapy is maintained over months to years on top of contemporary lipid-lowering and antithrombotic treatment. Yet clinical signals are not uniform across settings: benefit has been most consistent in chronic coronary disease, whereas findings in post-myocardial infarction and periprocedural settings remain more heterogeneous. In particular, CLEAR-SYNERGY complicates any simple chronic-versus-acute dichotomy, even though the overall long-term evidence base for low-dose colchicine remains supportive. We synthesize mechanistic and clinical data to propose a “time-window” framework that reconciles these observations. Colchicine rapidly dampens microtubule-dependent neutrophil activation, NET formation, and NLRP3 inflammasome signaling, but translation into fewer clinical events likely requires sustained exposure sufficient to modify plaque inflammation and vulnerability—processes that evolve more slowly than cath lab risk, which is compressed into hours and driven by thrombus burden, distal embolization, and microvascular injury already strongly influenced by procedural factors and potent background therapies. Clinically, the evidence supports colchicine as a long-horizon adjunct for secondary prevention in selected patients, with proactive management of early gastrointestinal intolerance and careful attention to drug–drug interactions to maximize persistence. Remaining priorities include precision selection, better discrimination between transient post-infarction inflammatory activation and persistent residual inflammatory risk, optimal timing and duration, and biomarker-guided implementation strategies.
Weng et al. (Mon,) studied this question.