Despite decades of advances in both lipid-lowering and antithrombotic therapies, a substantial residual risk of cardiovascular events persists in patients with established atherosclerotic cardiovascular disease (ASCVD). Chronic low-grade inflammation is a key driver of residual risk and has evolved to a compelling target for therapeutic intervention. In this updated meta-analysis, the authors synthesize data on the long-term efficacy and safety from six randomized controlled trials (RCTs), encompassing over 21’000 patients, to evaluate colchicine—an ancient anti-inflammatory agent—for secondary prevention of major adverse cardiovascular events (MACE) in patients with established ASCVD.

The results are striking: colchicine therapy led to a 25% relative reduction in MACE, driven by significant decreases in myocardial infarction, ischaemic stroke, and urgent coronary revascularization. Importantly, this benefit was not accompanied by an increase in adverse safety outcomes, including non-cardiovascular mortality, which has been a point of concern in prior studies.

Following the neutral results of the CLEAR-SYNERGY trial 1, these findings reinforce the anti-inflammatory hypothesis in ASCVD and position colchicine as a low-cost, broadly accessible therapy with the potential to reshape secondary prevention strategies in stabilized patients with established ASCVD.2,3 Importantly, the results largely align with an independent meta-analysis,4 with colchicine showing a consistent benefit across diverse vascular territories—post-myocardial infarction and post-stroke populations—further supporting its efficacy in diverse patient populations. However, the heterogeneity among trials, in terms of dosing, patient selection (specifically in the early phase following ST-segment elevation myocardial infarction, see CLEAR-SYNERGY trial results1), and concomitant therapies warrants attention.2,3 Moreover, patient adherence, tolerability over longer durations, and rare but serious side effects like myopathy or gastrointestinal intolerance remain important considerations for implementation in routine care.5,6

While colchicine will not supplant established therapies, its role as an adjunctive anti-inflammatory agent appears increasingly justified. Future research may focus on identifying the highest-risk phenotypes who stand to benefit most, and on integrating colchicine into more personalized prevention strategies. With robust evidence now in hand, the debate on its benefits may shift from “does it work?” to “how do we use it best?”.