Over recent years, inflammation has moved from an abstract cardiovascular risk factor to a modifiable therapeutic target. The concept of “residual inflammatory risk,” due to inflammation even after optimizing cardiovascular risk factors, is no longer speculative. In the Canakinumab Anti-Inflammatory Thrombosis Outcome Study (CANTOS), dampening interleukin-1β (IL-1β) activity within the innate immunity pathway reduced recurrent events following a myocardial infarction (MI). However, monoclonal antibodies targeting IL-1β proved impractical for broad use, shifting attention to colchicine, a classical, affordable anti-inflammatory drug that now serves a new purpose. Mechanistically, colchicine binds to β-tubulin in leukocytes, blunting neutrophil activation, inflammasome pathways, while reducing cytokines (IL-1β, IL-6, IL-18) and C-reactive protein.
Multiple randomized trials have tested whether adding low-dose colchicine daily can translate into fewer cardiac events through its anti-inflammatory properties. The results have been mixed. In the Colchicine Cardiovascular Outcomes Trial (COLCOT), patients randomized to colchicine within 30 days after MI experienced a 32% reduction in the composite outcome of cardiovascular death, resuscitated cardiac arrest, MI, stroke, or urgent revascularization. The Low-Dose Colchicine for Secondary Prevention of Cardiovascular Disease (LoDoCo) and LoDoCo2 trials confirmed benefit in patients with chronic stable coronary artery disease (CAD), including many with prior MI. At the same time, safety concerns have emerged due to a numerical increase in noncardiovascular mortality. , While these involved small numbers of events and lacked a clear mechanistic explanation, they underscored the need for thoughtful patient selection.
In contrast, the large Colchicine in Acute Myocardial Infarction trial, found no difference in outcomes with colchicine started within 72 hours of acute MI compared to placebo. Some have speculated that initiating therapy too early in the acute post-MI milieu or trial-specific factors such as predominant enrollment during the COVID-19 pandemic, may have obscured benefit. Ultimately, the aggregate data continue to support colchicine as beneficial in reducing cardiovascular events. A 2025 meta-analysis of 9 trials including over 30,000 patients found a 12% relative risk reduction in cardiovascular death, MI, or stroke (RR 0.88, 95% CI 0.81–0.95). Another pooled analysis of 6 trials with 21,800 patients reported a 25% reduction in major adverse cardiovascular events (HR 0.75, 95% CI 0.56–0.93). These benefits were observed without an increase in serious adverse events, aside from expected higher, but transient, rates of gastrointestinal symptoms. Collectively, these findings confirm a consistent benefit despite heterogeneity in trial design and timing of initiation.
On the basis of this strong yet nuanced evidence, the United States Food and Drug Administration approved low-dose colchicine, and both the European Society of Cardiology (ESC), the American College of Cardiology (ACC), and the American Heart Association (AHA) now provide a Class II recommendation, particularly for secondary prevention in CAD.
In a recent issue of The American Journal of Cardiology, Marano et al describe a large, retrospective study from a U.S. academic health system that adds crucial perspective. From 2018 to 2024 (1,796 patients encounters), colchicine was prescribed in fewer than 7% of post-MI patients, and in one-third of those cases, the indication was not related to CAD, most commonly gout or pericarditis. After adjustment, low-dose colchicine was not associated with reduced cardiovascular events. The authors wisely caution that the lack of observed benefit likely reflects- how and in whom- colchicine was used, as well as the scarcity of use and the heterogeneity of exposure. This was not a failure of colchicine, rather, it was a snapshot of its marginal presence in real-world practice.
Although rigorous adjustments, including propensity matching, were performed, unmeasured confounding undoubtedly remained. An additional limitation is the study timeframe, which overlaps with a period when colchicine lacked formal regulatory and strong guideline endorsement. Nonetheless, these findings remain highly informative. In short, this real-world study highlights an implementation gap more than an efficacy gap. The findings should not be viewed as a referendum against colchicine’s benefit, but as reflection of our slow adoption.
This raises an urgent question: why hasn’t colchicine gained traction despite guideline support and strong trial evidence? The answer lies in a convergence of clinical and structural barriers. First, clinician familiarity remains limited. Colchicine is often viewed as a drug for gout or pericarditis, rather than a component of antiatherosclerotic therapy. Second, the fear of complexity often outweighs the actual risk. Clinicians rightly note the drug’s narrow therapeutic index; however, the most cited concern- interaction with high-intensity statins- is largely overstated. In trials like LoDoCo2, myopathy rates were indistinguishable from placebo.
Of course, safety boundaries exist. Colchicine is contraindicated in patients with severe renal or hepatic impairment, where toxic accumulation can lead to serious cytopenia’s or myo-neuropathy. Outside of these clear exclusions, the primary red flag involves strong CYP3A4 inhibitors like clarithromycin, azole antifungals, or nirmatrelvir/ritonavir. In these cases, management is straightforward: for patients requiring a short course of these agents, a temporary 1 to 2 week pause is safer and more practical than dose adjustment. Third, guideline recommendations have been cautious assigning a Class II designation that might be interpreted as “permissible” rather than “priority.”
The study by Marano et al offers not only a mirror of current practice, but also a mandate for change. Generating evidence is only the first step; meaningful progress requires closing the gap between data and delivery. As trials evolve, the overarching message remains: colchicine reduces events in selected patients and can be implemented safely at minimal cost.
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