Low-dose Colchicine for atherosclerotic cardiovascular disease and the return of inflammation-targeted Pharmacotherapy

INTRODUCTION: Atherosclerotic cardiovascular disease (ASCVD) remains a leading cause of recurrent myocardial infarction, stroke, coronary revascularization, and cardiovascular death despite intensive lipid-lowering, antithrombotic, antihypertensive, and metabolic therapies. Residual inflammatory risk has emerged as an important therapeutic target, but translation into routine pharmacotherapy has been limited by cost, safety, route of administration, and uncertainty about patient selection. Low-dose colchicine, a plant-derived alkaloid with anti-inflammatory activity, has recently gained renewed interest as an oral adjunctive therapy for ASCVD risk reduction. AREAS COVERED: This review evaluates low-dose colchicine as inflammation-targeted pharmacotherapy for ASCVD. It discusses the clinical need, mechanistic basis, pharmacology, pivotal trial evidence, safety, drug-drug interactions, prescribing considerations, guideline positioning, real-world implementation, and unresolved questions. Key evidence includes the Colchicine Cardiovascular Outcomes Trial (COLCOT) after myocardial infarction, the Low-Dose Colchicine 2 (LoDoCo2) trial in chronic coronary disease, Food and Drug Administration (FDA) approval of Lodoco 0.5 mg once daily, and neutral evidence from Colchicine and Spironolactone in Patients with Myocardial Infarction/Organization for the Assessment of Strategies for Ischemic Syndromes 9 (CLEAR SYNERGY/OASIS-9) in acute myocardial infarction. EXPERT OPINION: Low-dose colchicine is best understood not as a replacement for lipid-lowering or antithrombotic therapy, but as a phenotype-dependent oral strategy for targeting residual inflammatory risk in selected ASCVD patients. This review contributes an integrated patient-selection framework that combines ischemic risk, chronic versus acute coronary setting, inflammatory phenotype, renal and hepatic safety, drug-interaction burden, tolerability, and patient preference. Its future clinical value will depend on careful patient selection, avoidance of interacting drugs, renal and hepatic safety assessment, clarification of its role after acute myocardial infarction, and real-world evidence showing whether trial efficacy translates into routine cardiovascular prevention.