Colchicine in cardiovascular medicine: Current perspectives on mechanisms and clinical therapeutics

Colchicine, an ancient anti-inflammatory alkaloid, has been successfully repurposed as a cardiovascular therapeutic agent. This review synthesizes the evolving clinical evidence and mechanistic underpinnings of colchicine's action across a spectrum of cardiovascular diseases. Robust data from randomized trials support its efficacy in reducing recurrences of acute and recurrent pericarditis. In atherosclerotic coronary artery disease, long-term, low-dose colchicine has been shown to significantly reduce major adverse cardiovascular events in patients with chronic coronary syndromes, prompting its inclusion in international guidelines. However, not all trials have yielded consistent results; for instance, in the setting of recurrent myocardial infarction, some studies have failed to demonstrate significant benefit, highlighting issues of reproducibility and patient heterogeneity that have emerged across cardiovascular outcome trials. Evidence for its utility in other settings, such as preventing postoperative atrial fibrillation or ischemia-reperfusion injury, remains inconsistent, and a clear dose-response relationship has yet to be established. The therapeutic benefits are primarily attributed to the pleiotropic anti-inflammatory mechanisms, including microtubule disruption, inhibition of the NLRP3 inflammasome, and modulation of neutrophil and macrophage functions. Despite a narrow therapeutic index, low-dose regimens are generally well-tolerated, with gastrointestinal disturbances being the most common adverse effect. Its pharmacokinetics, notably metabolism via CYP3A4 and transport by P-glycoprotein, necessitate caution regarding drug interactions and use in renal/hepatic impairment. Future research should focus on precise patient stratification, combination therapies, and exploring its potential in emerging cardiovascular indications, solidifying its role in anti-inflammatory therapy.