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Colchicine and anti-inflammatory therapy in cardiovascular disease

Inflammation in atherothrombosis, hsCRP, colchicine pharmacology and every cardiovascular indication, dosing in kidney and liver disease, drug interactions, toxicity, and the IL-1, IL-6, and other anti-inflammatory therapies tested in cardiovascular disease.

Atherosclerosis is an inflammatory disease of the arterial wall, and part of the risk that remains after low-density lipoprotein cholesterol (LDL-C) and blood pressure are controlled is inflammatory. Two randomized programs established this clinically: interleukin-1β (IL-1β) inhibition with canakinumab in CANTOS, and low-dose colchicine in COLCOT and LoDoCo2. Colchicine 0.5 mg once daily is approved in the United States to reduce cardiovascular events in adults with established atherosclerotic disease or multiple risk factors, and it is a first-line treatment for pericarditis. High-sensitivity C-reactive protein (hsCRP) is the standard marker of this inflammatory risk.

Related topics are covered in their own hubs: the treatment of pericarditis on Acute and recurrent pericarditis, the overall strategy for stable coronary disease on Chronic coronary disease, and risk-enhancing factors in primary prevention on Cardiovascular risk assessment.

Inflammation in atherothrombosis: from fatty streak to plaque rupture and erosion

Inflammation participates in every stage of atherosclerosis. Retention of apolipoprotein B–containing lipoproteins in the intima, and their oxidative modification, activates endothelial cells to express adhesion molecules (vascular cell adhesion molecule 1, intercellular adhesion molecule 1, and selectins) and chemokines such as monocyte chemoattractant protein 1. Monocytes enter the intima, differentiate into macrophages, and ingest modified lipoprotein to become foam cells. T lymphocytes, mast cells, and neutrophils join them. Smooth muscle cells migrate from the media, proliferate, and synthesize the collagen of the fibrous cap.

In the advanced plaque, macrophages secrete matrix metalloproteinases and cytokines that degrade collagen and inhibit its synthesis by smooth muscle cells. The cap thins over a necrotic lipid core, and a thin-cap fibroatheroma with abundant macrophages is the lesion most prone to rupture. Rupture exposes tissue factor and collagen, and thrombus forms. Plaque erosion, now a frequent substrate of acute coronary syndromes in the statin era, involves endothelial denudation over a matrix-rich lesion with fewer inflammatory cells. Neutrophils participate in the thrombus that forms on it through neutrophil extracellular traps (NETs), webs of DNA and granule proteins that the cells extrude. Inflammation therefore contributes to both principal mechanisms of coronary thrombosis, through different cells.

Cholesterol crystals form within the necrotic core and in macrophages, and they are potent activators of the NLRP3 (NOD-, LRR-, and pyrin domain–containing protein 3) inflammasome, linking the lipid and inflammatory pathways. Other inflammatory triggers include hyperglycemia, visceral adiposity, smoking, chronic kidney disease, periodontal and other chronic infections, and systemic autoimmune disease such as rheumatoid arthritis, psoriasis, and lupus. Clonal hematopoiesis of indeterminate potential is another: somatic mutations in genes such as TET2 in blood cells are associated with greater inflammasome activity and higher coronary risk.

Myocardial infarction itself is an inflammatory event. Necrotic myocytes release damage-associated molecular patterns that activate innate immunity, neutrophils and monocytes flood the infarct, and a systemic acute-phase response follows. The infarct also accelerates inflammation in remote plaques through mobilization of bone marrow and splenic leukocytes. This post-infarction inflammatory surge is part of the rationale for anti-inflammatory therapy after infarction, and its timing is central to the interpretation of the colchicine trials discussed below.

The NLRP3 inflammasome and the IL-1β, IL-6, and CRP cascade

The NLRP3 inflammasome is a cytosolic multiprotein complex of innate immune cells. Activation requires two signals. The priming signal, delivered through Toll-like receptors and nuclear factor κB (NF-κB), induces transcription of NLRP3 and of pro-IL-1β. The activation signal, delivered by cholesterol crystals, urate crystals, extracellular adenosine triphosphate (ATP), potassium efflux, reactive oxygen species, and mitochondrial injury, causes NLRP3 to oligomerize with the adaptor protein ASC (apoptosis-associated speck-like protein containing a caspase recruitment domain) and pro-caspase-1. Active caspase-1 cleaves pro-IL-1β and pro-interleukin-18 (IL-18) into their secreted forms and cleaves gasdermin D, which forms membrane pores and causes pyroptotic cell death.

IL-1β is the proximal cytokine. It induces interleukin-6 (IL-6), and IL-6 drives hepatic synthesis of C-reactive protein (CRP), fibrinogen, and other acute-phase proteins. This sequence, NLRP3 to IL-1β to IL-6 to CRP, is the central pathway of residual inflammatory risk. Human genetics support its causal role: variants in the IL-6 receptor gene that reduce IL-6 signaling are associated with lower coronary risk, whereas variants that raise CRP concentrations alone are not. CRP is therefore a marker of the pathway, not a target, and therapies are judged by whether they inhibit the pathway upstream of it.

The inflammatory pathway in atherothrombosis and the therapies tested at each step.

High-sensitivity CRP and residual inflammatory risk

CRP is an acute-phase pentraxin produced by the liver under IL-6 stimulation. Standard CRP assays detect the high concentrations of infection and systemic inflammation. High-sensitivity assays measure the low range, below about 10 mg/L, that is relevant to cardiovascular risk. Both assays measure the same molecule, and hsCRP results are reported in mg/L. Some laboratories report standard CRP in mg/dL, and a value of 0.3 mg/dL equals 3 mg/L.

The 2003 statement from the Centers for Disease Control and Prevention (CDC) and the American Heart Association (AHA) defined the categories still in use: below 1 mg/L, lower relative risk; 1 to 3 mg/L, average relative risk; and above 3 mg/L, higher relative risk. Trials and statements use a separate threshold of 2 mg/L to define residual inflammatory risk in statin-treated patients. Measurement is made in a metabolically stable patient without acute illness, and the average of two measurements, fasting or nonfasting and optimally 2 weeks apart, is used. A value above 10 mg/L reflects an acute or chronic inflammatory process. The test is repeated after it resolves, and a source of infection or inflammation is sought.

hsCRP categories, thresholds, and their use in cardiovascular risk assessment. The CDC/AHA categories do not overlap; the 2 mg/L treatment threshold is a separate cutoff that overlaps them. Values are in mg/L; 1 mg/dL equals 10 mg/L.

Residual inflammatory risk. In patients receiving statins, hsCRP predicts recurrent events as strongly as LDL-C, and often more strongly. In a pooled analysis of 31,245 statin-treated patients in PROMINENT, REDUCE-IT, and STRENGTH, the highest quartile of baseline hsCRP, compared with the lowest, was associated with more major adverse cardiovascular events (adjusted hazard ratio 1.31), cardiovascular death (2.68), and all-cause death (2.42). The relationship of LDL-C quartile to these outcomes was neutral or weak. The term residual inflammatory risk describes an hsCRP of 2 mg/L or more despite statin therapy, and residual cholesterol risk describes an LDL-C above goal. The two coexist, but inflammatory risk is more common in contemporary treated populations.

hsCRP in primary prevention. JUPITER randomized 17,802 adults with LDL-C below 130 mg/dL and hsCRP of 2 mg/L or more to rosuvastatin 20 mg or placebo. The primary endpoint fell from 1.36 to 0.77 events per 100 person-years (hazard ratio 0.56), and rosuvastatin lowered hsCRP by 37% and LDL-C by 50%. The trial established that patients selected by hsCRP benefit from statin therapy, although it did not isolate an anti-inflammatory effect. The role of hsCRP and other markers as risk-enhancing factors when a statin decision is uncertain is covered on the Cardiovascular risk assessment page.

The 2025 ACC scientific statement. The ACC statement on inflammation and cardiovascular disease concluded that the evidence linking inflammation with atherosclerotic disease is clinically actionable. It recommends universal hsCRP screening, together with cholesterol, in both primary and secondary prevention. It also recommends intensifying statin therapy when hsCRP remains above 2 mg/L and adding low-dose colchicine to lipid lowering in chronic stable atherosclerosis. Colchicine has not proved effective when started at the time of acute ischemia and is avoided in significant liver or kidney disease. A scientific statement is not a guideline, and no ACC/AHA guideline requires an elevated hsCRP before colchicine is prescribed.

Effect of treatment on hsCRP. Statins lower hsCRP independently of their effect on LDL-C (by 37% with rosuvastatin 20 mg in JUPITER). Weight loss, physical activity, smoking cessation, and glucagon-like peptide-1 (GLP-1) receptor agonists also lower it. In an open-label study of 44 patients with stable coronary disease and hsCRP of 2 mg/L or more despite aspirin and atorvastatin, colchicine 0.5 mg twice daily for 4 weeks lowered hsCRP by 60%, from 4.58 to 1.78 mg/L. A level below 2 mg/L was reached by 70% of patients. In CLEAR SYNERGY, colchicine lowered CRP at 3 months by 1.28 mg/L more than placebo without reducing events. A fall in hsCRP shows that a drug engages the pathway, but it is not proof of clinical benefit.

Colchicine pharmacology: tubulin binding, neutrophils, and the inflammasome

Colchicine is an alkaloid extracted from Colchicum autumnale (autumn crocus) and Gloriosa superba. Its primary action is binding to tubulin. The drug attaches to soluble β-tubulin at the colchicine-binding site, at the interface with α-tubulin. The tubulin-colchicine complex caps the growing end of microtubules and prevents further polymerization. At high concentrations, microtubules depolymerize. Because microtubules are required for cell shape, motility, intracellular transport, and mitotic spindle formation, colchicine affects many cell functions, and its toxicity in overdose is antimitotic.

The anti-inflammatory effect at low doses rests on the neutrophil. Colchicine concentrates in leukocytes at levels well above plasma, which allows an effect at doses that leave most other cells unaffected. In neutrophils, it impairs chemotaxis, adhesion to endothelium, degranulation, superoxide generation, and the release of NETs. It alters the distribution of E-selectin on endothelial cells and reduces shedding of L-selectin from neutrophils, so that neutrophil rolling and recruitment are reduced. It reduces the formation of neutrophil-platelet aggregates and inhibits platelet activation.

Colchicine inhibits the inflammasome indirectly. Assembly of NLRP3 depends on microtubule-dependent transport that brings mitochondria-associated ASC into contact with NLRP3 on the endoplasmic reticulum. By disrupting this transport, colchicine reduces caspase-1 activation and the release of IL-1β and IL-18, with downstream reductions in IL-6 and CRP. In patients with an acute coronary syndrome, a single course of colchicine (1 mg followed by 0.5 mg an hour later) reduced the transcoronary gradients of IL-1β, IL-18, and IL-6, measured between the coronary sinus and the aortic root, by 40% to 88%. A nonrandomized coronary computed tomography angiography study after an acute coronary syndrome compared colchicine 0.5 mg daily for 1 year with optimal medical therapy alone. Colchicine was associated with a greater reduction in low-attenuation plaque volume (−40.9% vs −17.0%) and hsCRP, without a difference in LDL-C reduction.

Colchicine is not an analgesic, does not affect uric acid concentrations, and does not lower LDL-C. Its effect in gout and familial Mediterranean fever (FMF) comes from the same inhibition of neutrophil recruitment and inflammasome activity, triggered in gout by urate crystals and in FMF by pyrin mutations.

Pharmacokinetics of colchicine

Colchicine is absorbed from the jejunum and ileum, with absolute bioavailability of about 45% and wide interindividual variation. Peak plasma concentration is reached about 1 hour after a dose. Food has no meaningful effect. Secondary plasma peaks 3 to 36 hours after a dose reflect intestinal secretion and reabsorption and enterohepatic recirculation. Colchicine distributes extensively into tissues and binds to tubulin in leukocytes, so plasma concentrations are low and poorly reflect tissue exposure.

Pharmacokinetics of oral colchicine, from the US prescribing information for COLCRYS and LODOCO.

Older adults have higher exposure. In a small pharmacokinetic study cited in the COLCRYS label, peak levels and area under the curve were about twice as high in women with a mean age of 83 years as in young men. The difference was attributed largely to lower kidney function. Colchicine does not inhibit or induce cytochrome P450 enzymes, so it does not change the levels of other drugs. Its interactions are one-directional: other drugs raise colchicine exposure.

US formulations and FDA-labeled indications

Colchicine was marketed in the United States long before modern drug approval. In 2009, the Food and Drug Administration (FDA) approved COLCRYS (colchicine 0.6-mg tablets) for gout and FMF, and unapproved single-ingredient products were later removed from the market. In June 2023, LODOCO (colchicine 0.5-mg tablets) became the first anti-inflammatory drug approved to reduce cardiovascular events, on the basis of LoDoCo2.

Colchicine products in the United States. The cardiovascular trials used 0.5-mg tablets; the 2025 ACC/AHA acute coronary syndrome guideline states that daily dosing of 0.5 mg or 0.6 mg may be considered.

The 0.6-mg generic tablet is the widely stocked form, and it is often used for cardiovascular prevention when the branded 0.5-mg product is not covered. The 0.6-mg dose was not the dose tested in the outcome trials. The corrected 2023 chronic coronary disease guideline recommends 0.5 mg daily, and the 2025 acute coronary syndrome guideline accepts 0.5 or 0.6 mg daily. Half of a scored 0.6-mg tablet (0.3 mg) is the step used in the label for dose reduction with interacting drugs and kidney impairment.

Randomized trials of colchicine in coronary and cerebrovascular disease

Randomized outcome trials of long-term low-dose colchicine in atherosclerotic disease. HR indicates hazard ratio (95% confidence interval); MI, myocardial infarction; ACS, acute coronary syndrome; PCI, percutaneous coronary intervention.

Colchicine in chronic coronary disease: LoDoCo and LoDoCo2

The first outcome trial was LoDoCo. Its rationale was the finding of activated neutrophils in culprit plaques of patients with unstable coronary disease. The 532 patients had stable coronary disease, and 93% took antiplatelet therapy and 95% took statins. Colchicine 0.5 mg daily reduced the composite of acute coronary syndrome, out-of-hospital cardiac arrest, or noncardioembolic ischemic stroke from 16.0% to 5.3% over a median of 3 years (hazard ratio 0.33; number needed to treat 11). The benefit came mainly from fewer acute coronary syndromes unrelated to stents. The trial was small and open label, and 11% of patients assigned to colchicine stopped it within 30 days because of intestinal intolerance.

LoDoCo2 was the confirmatory trial. It enrolled 5,522 patients aged 35 to 82 years in Australia and the Netherlands with angiographically proven coronary disease or a coronary artery calcium score of at least 400 Agatston units, clinically stable for at least 6 months. Every patient first took open-label colchicine for 1 month. About 15% of those entering the run-in did not proceed to randomization, most because of gastrointestinal or other adverse effects. The randomized population therefore consisted of patients who tolerated the drug, which affects both the efficacy and the safety estimates.

Over a median of 28.6 months, the primary composite of cardiovascular death, spontaneous myocardial infarction, ischemic stroke, or ischemia-driven coronary revascularization occurred in 6.8% with colchicine and 9.6% with placebo. The rates were 2.5 and 3.6 events per 100 person-years (hazard ratio 0.69; number needed to treat 36 over the trial). The key secondary composite of cardiovascular death, spontaneous myocardial infarction, or ischemic stroke was also reduced (4.2% vs 5.7%; hazard ratio 0.72). Myocardial infarction (3.0% vs 4.2%; hazard ratio 0.70) and ischemia-driven revascularization (4.9% vs 6.4%; hazard ratio 0.75) fell significantly. Ischemic stroke (0.6% vs 0.9%) and cardiovascular death (0.7% vs 0.9%) were numerically lower, without statistical significance. About 84% of patients had a prior acute coronary syndrome, and the findings were consistent in that group.

Two signals temper the result. Death from noncardiovascular causes was more frequent with colchicine (0.7 vs 0.5 events per 100 person-years; hazard ratio 1.51, 95% confidence interval 0.99 to 2.31), and all-cause death did not differ. No single cause explained the excess, and it was not seen consistently in other trials. Myalgia was reported in 21.2% with colchicine and 18.5% with placebo (hazard ratio 1.15), a small excess that appears in the LODOCO label. The FDA approval in 2023 rests on this trial, and the label's indication extends to adults with multiple risk factors without established disease, a population that LoDoCo2 did not study.

The place of colchicine in the overall management of stable coronary disease, alongside lipid lowering, antiplatelet therapy, and antianginal drugs, is covered on the Chronic coronary disease page.

Colchicine after myocardial infarction: COLCOT, COPS, and CLEAR SYNERGY

COLCOT. COLCOT randomized 4,745 patients within 30 days of myocardial infarction, a median of about 14 days after the event, to colchicine 0.5 mg daily or placebo. Most had undergone PCI and received aspirin, a second antiplatelet drug, and a statin. Over a median of 22.6 months, the primary composite of cardiovascular death, resuscitated cardiac arrest, myocardial infarction, stroke, or urgent hospitalization for angina leading to revascularization occurred in 5.5% with colchicine and 7.1% with placebo (hazard ratio 0.77, 95% confidence interval 0.61 to 0.96). The effect came from stroke (hazard ratio 0.26) and urgent hospitalization for angina leading to revascularization (hazard ratio 0.50). Myocardial infarction (hazard ratio 0.91) and cardiovascular death (hazard ratio 0.84) were not significantly reduced. Diarrhea did not differ (9.7% vs 8.9%), but pneumonia reported as a serious adverse event was more frequent (0.9% vs 0.4%).

COPS. COPS, from Australia, randomized 795 patients with an acute coronary syndrome and angiographic coronary disease during the index admission to colchicine (0.5 mg twice daily for 1 month, then daily for 11 months) or placebo. The primary composite of all-cause death, acute coronary syndrome, ischemia-driven urgent revascularization, and noncardioembolic ischemic stroke occurred in 24 patients with colchicine and 38 with placebo (P=0.09). Total deaths were more frequent with colchicine (8 vs 1; P=0.017), including 5 noncardiovascular deaths vs none. In a post hoc analysis that replaced all-cause death with cardiovascular death, the composite was lower with colchicine. The trial was underpowered, and the mortality imbalance rested on few events.

CLEAR SYNERGY. Also known as OASIS 9, this trial was the largest trial of colchicine started early after myocardial infarction. It used a 2-by-2 factorial design that also tested spironolactone, and it enrolled 7,062 patients at 104 centers in 14 countries within 72 hours of PCI for myocardial infarction, most with ST-elevation myocardial infarction (STEMI). Over a median of 3 years, the primary composite of cardiovascular death, recurrent myocardial infarction, stroke, or unplanned ischemia-driven revascularization occurred in 9.1% with colchicine and 9.3% with placebo (hazard ratio 0.99, 95% confidence interval 0.85 to 1.16). No component differed. Colchicine lowered CRP at 3 months (adjusted difference −1.28 mg/L), confirming that it was taken and engaged its target. Diarrhea was more frequent (10.2% vs 6.6%), and serious infections were not.

The trial ran through the coronavirus disease 2019 (COVID-19) pandemic, and discontinuation of study drug was substantial, which reduces the power to detect a modest effect. Even so, the confidence interval excludes the point estimate of benefit seen in COLCOT. CLEAR SYNERGY does not support routine initiation of colchicine in the first days after myocardial infarction. The 2025 ACC/AHA acute coronary syndrome guideline does not cite the trial. Discharge therapy after infarction is covered on the ST-elevation myocardial infarction and Non-ST-elevation acute coronary syndrome pages.

Interpreting the discordant trials: timing, population, and adherence

The trials can be reconciled in several ways, none proven. The leading explanation is timing and population. LoDoCo2 enrolled patients at least 6 months from an acute event, and COLCOT a median of 2 weeks after infarction. CLEAR SYNERGY started treatment within 72 hours of PCI, when the inflammatory response to infarction is dominated by myocardial healing and may not be the same target as chronic plaque inflammation. Reduced adherence during the pandemic adds uncertainty to CLEAR SYNERGY.

Subgroup data from COLCOT appear to point in the opposite direction. In a post hoc analysis, the benefit was concentrated in patients who started colchicine within 3 days of infarction (hazard ratio 0.52), with no significant effect when it was started on days 4 to 7 (hazard ratio 0.96) or after day 8 (hazard ratio 0.82). This analysis was not randomized by timing, the subgroups were small, and the large randomized test of early treatment, CLEAR SYNERGY, was neutral. The 2025 ACC scientific statement and US labeling position colchicine as long-term therapy for clinically stable patients, not as treatment for the acute event.

Endpoint composition also differs. COLCOT's benefit came mostly from urgent hospitalization for angina and stroke, endpoints with some subjectivity and low event counts. LoDoCo2 reduced myocardial infarction as well. Neither trial reduced cardiovascular death, and the combined trial evidence shows no effect on all-cause mortality. Colchicine is therefore best described as reducing nonfatal ischemic events, principally myocardial infarction, stroke, and urgent revascularization, in stable patients.

Meta-analyses of long-term colchicine in atherosclerotic disease

Pooled analyses consistently show fewer myocardial infarctions and strokes with long-term colchicine, no effect on mortality, and more gastrointestinal adverse effects. Estimates shrank modestly after CLEAR SYNERGY and CONVINCE were added.

Meta-analyses of long-term colchicine. RR indicates risk ratio; HR, hazard ratio; MI, myocardial infarction.

The 2025 Cochrane review of secondary prevention found high-certainty evidence that colchicine reduces myocardial infarction by about 9 events per 1,000 patients and stroke by about 8 per 1,000, without an increase in serious adverse events. Mortality and coronary revascularization were not reduced. The primary prevention review, whose small trials were mostly at high risk of bias and focused largely on patients with liver disease, found the evidence very uncertain for every outcome. There is no randomized evidence that colchicine prevents a first cardiovascular event, so the US label's inclusion of patients with multiple risk factors but no established disease rests on extrapolation.

Colchicine after stroke: CONVINCE and CHANCE-3

Stroke reduction in COLCOT and LoDoCo2 prompted trials in patients with cerebrovascular disease. CONVINCE randomized 3,154 patients with non-severe, noncardioembolic ischemic stroke or high-risk transient ischemic attack to open-label colchicine 0.5 mg daily plus usual care or usual care alone. The trial stopped before its planned number of events because of pandemic-related funding constraints. The primary composite of recurrent ischemic stroke, myocardial infarction, cardiac arrest, or hospitalization for unstable angina occurred in 9.8% with colchicine and 11.7% without it (hazard ratio 0.84, 95% confidence interval 0.68 to 1.05). CRP was lower with colchicine at every time point, and serious adverse events were similar.

CHANCE-3, in China, tested a different question: short-term colchicine started within 24 hours of a minor-to-moderate ischemic stroke or transient ischemic attack in patients with hsCRP of 2 mg/L or more. Colchicine 0.5 mg twice daily for 3 days, then daily for 90 days, did not reduce new stroke at 90 days (6.3% vs 6.5%; hazard ratio 0.98). Like CLEAR SYNERGY, it shows that colchicine started at the time of an acute event does not prevent early recurrence. Stroke reduction in the coronary trials was a secondary finding and was driven by small numbers, but it is consistent across the pooled analyses. Colchicine is not a guideline-recommended therapy for secondary stroke prevention in the United States.

Colchicine around PCI: periprocedural injury and in-stent restenosis

PCI injures the vessel wall, and neutrophil recruitment contributes to periprocedural myocardial injury and to neointimal hyperplasia. COLCHICINE-PCI randomized patients referred for possible PCI to colchicine 1.8 mg or placebo before the procedure. Among the 400 who underwent PCI, PCI-related myocardial injury did not differ (57.3% vs 64.2%), and neither did death, myocardial infarction, or target-vessel revascularization at 30 days. Colchicine attenuated the rise in IL-6 and hsCRP at 24 hours. Acute preprocedural colchicine has no role in PCI.

In-stent restenosis is a separate question. In 196 patients with diabetes who received bare-metal stents because a drug-eluting stent was contraindicated, colchicine 0.5 mg twice daily for 6 months reduced angiographic restenosis from 33% to 16% (odds ratio 0.38) and late lumen area loss on intravascular ultrasound. The trial predates current drug-eluting stents, in which restenosis rates are far lower, and it is hypothesis-generating. In LoDoCo2 and COLCOT, which enrolled patients largely after drug-eluting stent implantation, ischemia-driven revascularization fell, but the trials did not report restenosis separately.

Postoperative atrial fibrillation, heart failure, and other cardiac uses

Atrial fibrillation after cardiac surgery. Pericardial inflammation contributes to postoperative atrial fibrillation (AF). In the COPPS AF substudy of 336 patients in sinus rhythm, colchicine started on the third postoperative day reduced AF within 1 month from 22.0% to 12.0% (number needed to treat 11) and shortened hospital stay. In COPPS-2, colchicine started 48 to 72 hours before surgery did not significantly reduce postoperative AF in the intention-to-treat analysis (33.9% vs 41.7%), although it did in the prespecified on-treatment analysis (27.0% vs 41.2%). Adverse events, mainly gastrointestinal, were more frequent (20.0% vs 11.7%). Colchicine is not part of the standard prophylaxis regimens for postoperative AF, which are beta-blockers and amiodarone. Prophylaxis is covered on the Atrial fibrillation page.

Noncardiac thoracic surgery. COP-AF randomized 3,209 patients aged 55 years or older having major noncardiac thoracic surgery to colchicine 0.5 mg twice daily or placebo, from 4 hours before surgery for 10 days. Clinically important perioperative AF (6.4% vs 7.5%; hazard ratio 0.85) and myocardial injury after noncardiac surgery (18.3% vs 20.3%; hazard ratio 0.89) were not significantly reduced. Noninfectious diarrhea was more than three times as frequent (8.3% vs 2.4%).

Atrial fibrillation after ablation. Small randomized studies from a single center found fewer early recurrences after pulmonary vein isolation with a short course of colchicine. The effect has not been confirmed in larger trials, and colchicine is not a standard part of ablation care.

Heart failure. Inflammation, measured by hsCRP and IL-6, predicts incident and worsening heart failure, especially with preserved ejection fraction. Colchicine has no proven role. In CANTOS, canakinumab produced a dose-dependent trend toward fewer heart failure hospitalizations. Anti-tumor necrosis factor therapy with high-dose infliximab, in contrast, worsened outcomes in moderate to severe heart failure in the ATTACH trial, and no anti-inflammatory drug is approved for heart failure. IL-6 inhibition in heart failure with preserved ejection fraction is being tested in the HERMES trial of ziltivekimab.

Myocarditis. Colchicine is not a treatment for myocarditis. In myopericarditis with predominant pericardial involvement, it is used as for pericarditis, as described on the Acute and recurrent pericarditis page.

Colchicine in pericarditis and after cardiac surgery

Pericarditis is the indication with the strongest evidence for colchicine, and the complete treatment pathway, including tapering, recurrence, corticosteroids, and IL-1 blockade, is covered on the Acute and recurrent pericarditis page. Colchicine added to aspirin or a nonsteroidal anti-inflammatory drug (NSAID) roughly halves the risk of recurrence after a first episode (in ICAP, incessant or recurrent pericarditis 16.7% vs 37.5%; number needed to treat 4). The same effect is seen after a first or later recurrence (CORP and CORP-2). The 2025 ACC guidance and the 2025 European Society of Cardiology (ESC) guideline place it with aspirin or an NSAID as first-line therapy for acute and recurrent pericarditis.

The regimen differs from cardiovascular prevention. In the United States, the 2025 ACC guidance gives 0.6 mg twice daily, or 0.6 mg once daily below 70 kg or with severe renal or hepatic impairment. Treatment lasts 3 months after a first episode and 6 to 12 months after a recurrence, and colchicine is the last drug stopped. The guidance reduces the dose to 0.3 to 0.6 mg daily with potent P-glycoprotein or CYP3A4 inhibitors. The 0.6-mg product is used because the 0.5-mg product is labeled only for cardiovascular risk reduction, and pericarditis is an off-label use of both.

After cardiac surgery, perioperative colchicine reduced the postpericardiotomy syndrome in COPPS (8.9% vs 21.1%) and COPPS-2 (19.4% vs 29.4%; number needed to treat 10). In COPPS-2, the regimen was 0.5 mg twice daily at 70 kg or more, or once daily below 70 kg, started 48 to 72 hours before surgery and continued for 1 month. The gastrointestinal adverse effects that came with it (number needed to harm 12) limit routine use, and it did not reduce postoperative pericardial or pleural effusion. After myocardial infarction, pericarditis is treated with high-dose aspirin, and the 2025 ACC/AHA acute coronary syndrome guideline suggests colchicine 0.5 to 0.6 mg once or twice daily for 3 months in persistent or late pericarditis.

Guideline recommendations for colchicine in atherosclerotic disease

US and European guidelines agree that colchicine reduces events, but they differ in strength. The US documents rate it Class 2b, whereas the 2024 ESC chronic coronary syndrome guideline rates it Class 2a. The 2023 AHA/ACC chronic coronary disease guideline cites the narrow therapeutic index of colchicine and its CYP3A4 and P-glycoprotein interactions. It limits use to patients who remain at very high risk despite maximally tolerated guideline-directed therapy until further data become available.

Guideline and regulatory positions on low-dose colchicine for atherosclerotic disease. The 2025 ACS guideline recommendation cites COLCOT, COPS, and LoDoCo2; it does not cite CLEAR SYNERGY.

The 2025 ACC/AHA acute coronary syndrome guideline lists the same exclusions as the US label: blood dyscrasias, creatinine clearance below 15 mL/min, severe hepatic impairment, and concomitant P-glycoprotein or strong CYP3A4 inhibitors. It also states that additional data are needed to confirm the efficacy of colchicine after an acute coronary syndrome. No US guideline recommends colchicine for primary prevention, for acute stroke, or for treatment during the acute phase of myocardial infarction.

Patient selection, initiation, and duration of therapy

The trial populations define the patients in whom benefit has been shown: adults with clinically stable coronary disease, either at least 6 months after an acute event or about 2 weeks after myocardial infarction. They were already receiving statin and antiplatelet therapy, had adequate kidney and liver function, and tolerated the drug.

Features that favor treatment are recurrent ischemic events despite optimized therapy and LDL-C at goal with residual risk. An hsCRP of 2 mg/L or more on repeated measurement marks residual inflammatory risk, but it does not select patients for colchicine. The coronary outcome trials did not use hsCRP as an entry criterion. CHANCE-3, a stroke trial that required an hsCRP of 2 mg/L or more, was neutral, and the predictive value of hsCRP for colchicine benefit is unproven. Features that weigh against treatment are a creatinine clearance below 30 mL/min, liver disease, an unavoidable interacting drug, polypharmacy in frail older adults, prior gastrointestinal intolerance, cytopenia, and an acute coronary event within the past few days.

Baseline evaluation. A complete blood count, serum creatinine with estimated creatinine clearance, liver enzymes, and a medication review for CYP3A4 and P-glycoprotein inhibitors are obtained. The LODOCO label does not require routine laboratory monitoring, but kidney function is rechecked when it may have changed. New gastrointestinal symptoms, muscle weakness, or myalgia prompt evaluation for toxicity, with creatine kinase and blood counts.

Initiation and tolerability. Colchicine is started at 0.5 mg (or 0.6 mg) once daily. Gastrointestinal effects usually appear in the first weeks and often settle. Patients are told that diarrhea or vomiting is a reason to stop the drug and seek advice, because gastrointestinal symptoms can be the first sign of toxicity.

Duration. In the trials, colchicine was continued for 2 to 3 years, and there are no data on stopping. It is continued indefinitely in patients who tolerate it, in the same way as other secondary prevention therapy. It is withheld during intercurrent illness that causes dehydration, acute kidney injury, or vomiting, and while a strong interacting drug such as clarithromycin is given.

Colchicine dosing by indication, kidney function, and interacting drugs

Colchicine doses vary widely by indication, from 0.5 mg daily for cardiovascular prevention to 2.4 mg daily in FMF. The calculator applies the US labels (LODOCO for cardiovascular prevention and COLCRYS for gout and FMF), the 2025 ACC pericarditis guidance, and the COPPS-2 regimen to the patient's kidney function, liver function, and interacting drugs. Creatinine clearance is estimated by the Cockcroft-Gault equation, which is the method used in the labels.

Doses from the LODOCO and COLCRYS prescribing information, the 2025 ACC pericarditis guidance, and the COPPS-2 trial. In pericarditis, the calculator gives once-daily dosing below 70 kg, as in the 2025 ACC guidance; ICAP and CORP-2 used once-daily dosing at 70 kg or less. The label contraindicates strong inhibitors with any renal impairment, defined as creatinine clearance below 80 mL/min. The calculator does not cover combined interacting drugs, pregnancy, or pediatric dosing.

Colchicine doses by indication. Pericarditis and postpericardiotomy prophylaxis are off-label uses in the United States.

Dosing in kidney and liver disease

Kidney function is the main determinant of colchicine safety. In the LODOCO pharmacokinetic study, exposure was similar with normal function and mild impairment but doubled in moderate and severe impairment. In patients on dialysis, clearance is about 75% lower than normal and the elimination half-life is prolonged. Colchicine is not removed by hemodialysis, so a dialysis session does not reverse accumulation.

Colchicine adjustment by kidney function. The bands follow the COLCRYS label categories of mild (50 to 80 mL/min), moderate (30 to 50 mL/min), and severe (below 30 mL/min) impairment; the LODOCO label defines only the contraindication below 15 mL/min. Creatinine clearance is estimated by the Cockcroft-Gault equation; eGFR indexed to body surface area can misclassify small or older patients.

Hepatic impairment. Colchicine is metabolized in the liver and excreted in bile, and clearance is reduced, with a prolonged half-life, in some patients with cirrhosis. Severe hepatic impairment is a contraindication to LODOCO, and COLCRYS recommends dose reduction in severe impairment and monitoring in mild to moderate impairment. LODOCO is avoided when any degree of hepatic impairment is combined with a P-glycoprotein inhibitor or a strong or moderate CYP3A4 inhibitor. Combined kidney and liver impairment carries the highest risk.

Older adults. Age itself is not a contraindication. More than half of LoDoCo2 participants were 65 years or older, with no difference in safety or efficacy. Lower creatinine clearance, low body weight, polypharmacy, and frailty account for most of the higher risk of toxicity in older patients, and these are assessed individually. In pericarditis, the 2015 ESC guideline halves the colchicine dose in older adults, and the 2025 ESC guideline does so in selected patients.

Drug interactions: CYP3A4 and P-glycoprotein

Colchicine is metabolized by CYP3A4 and exported from enterocytes, hepatocytes, and renal tubular cells by P-glycoprotein. Drugs that inhibit either pathway raise colchicine concentrations, sometimes several-fold, and fatal toxicity has been reported at therapeutic colchicine doses with clarithromycin and with cyclosporine. The COLCRYS label applies its dose adjustments to patients who are taking an interacting drug or who completed one within the prior 14 days.

Drug interactions of colchicine from the LODOCO and COLCRYS prescribing information. Amiodarone, dronedarone, carvedilol, quinidine, and ticagrelor inhibit P-glycoprotein to varying degrees and are not listed in the labels; they warrant monitoring for toxicity.

Interactions in cardiovascular practice. Diltiazem and verapamil are moderate CYP3A4 inhibitors, and myopathy and neuropathy have been reported with both. When a nondihydropyridine calcium channel blocker is needed in a patient with reduced kidney function, colchicine is avoided, or the calcium channel blocker is replaced. Ranolazine is a P-glycoprotein inhibitor and is contraindicated with LODOCO. Nearly all patients in the colchicine outcome trials received a statin, and the combination is standard, but statin-associated muscle symptoms and colchicine myopathy can be confused. Muscle weakness, a rising creatine kinase, or an abnormal neurologic examination in a patient taking both drugs is evaluated for colchicine toxicity, particularly when kidney function has declined.

Interactions from other prescribers. Many dangerous combinations arise when another clinician prescribes a short course of a macrolide or an azole antifungal, or when an HIV regimen is started or changed. Clarithromycin is the classic cause of fatal colchicine toxicity. Colchicine is held for the duration of a course of clarithromycin. Electronic interaction checkers flag many of these combinations but do not account for kidney function. Review of the full medication list at initiation and at every new prescription, with a current creatinine clearance, addresses this gap. Patients are given a list of the antibiotics and antifungals that interact, and are told to avoid grapefruit products.

Adverse effects of colchicine

Gastrointestinal effects. Diarrhea, nausea, cramping, and vomiting are the most common adverse effects, and they are dose related. At 0.5 mg once daily, diarrhea rates in COLCOT did not differ from placebo (9.7% vs 8.9%). In CLEAR SYNERGY, diarrhea was more frequent (10.2% vs 6.6%). Gastrointestinal effects were more common with the twice-daily regimens of COPPS-2 (adverse events 20.0% vs 11.7%) and COP-AF (noninfectious diarrhea 8.3% vs 2.4%). In the 2025 Cochrane review, gastrointestinal adverse events were increased (risk ratio 1.68), and the events were typically mild and transient. Because gastrointestinal symptoms are also the first stage of toxicity, new diarrhea or vomiting in a patient with kidney impairment or a new interacting drug is treated as toxicity until shown otherwise.

Myopathy and neuromyopathy. Colchicine myopathy is a vacuolar myopathy, often accompanied by an axonal neuropathy (neuromyopathy). It presents with proximal weakness, elevated creatine kinase, and sometimes paresthesia and loss of reflexes, usually after weeks to months of therapy in patients with kidney impairment or an interacting drug. Rhabdomyolysis occurs, especially with statins, fibrates, and cyclosporine. Weakness resolves over weeks after colchicine is stopped. Myalgia without weakness was slightly more common with colchicine in LoDoCo2 (21.2% vs 18.5%).

Myelosuppression. Leukopenia, granulocytopenia, thrombocytopenia, pancytopenia, and aplastic anemia occur with accumulation and in overdose. Preexisting blood dyscrasias are a contraindication to LODOCO. A blood count is obtained at baseline and when symptoms suggest toxicity.

Infection. Pneumonia reported as a serious adverse event was more frequent with colchicine in COLCOT (0.9% vs 0.4%). Serious infection was not increased in CLEAR SYNERGY, CONVINCE, or the pooled analyses, and serious adverse events overall were not increased in the 2025 Cochrane review. In COP-AF, sepsis or infection was numerically more frequent (6.4% vs 5.2%; hazard ratio 1.24, not significant).

Noncardiovascular death. A numerical excess of noncardiovascular death appeared in LoDoCo2 (hazard ratio 1.51, 95% confidence interval 0.99 to 2.31) and in COPS (5 vs 0 deaths), and the 2021 meta-analysis showed a borderline increase (risk ratio 1.38). No mechanism or consistent cause, such as infection or cancer, explained it. The 2025 meta-analysis that added CLEAR SYNERGY and CONVINCE found no increase (risk ratio 1.08), and all-cause mortality is neutral in every pooled analysis. The signal remains unconfirmed. The 2023 AHA/ACC chronic coronary disease guideline notes the trend in LoDoCo2, and the 2025 ACC/AHA acute coronary syndrome guideline states that the signal requires further study.

Other effects. Rash, alopecia (mainly after overdose), and reversible azoospermia have been reported. Acute kidney injury appears in the postmarketing experience of the LODOCO label.

Colchicine toxicity and overdose

Colchicine has a narrow therapeutic index. Toxicity arises in two settings: intentional or accidental overdose, and accumulation at therapeutic doses because of kidney or liver impairment or an interacting drug. The COLCRYS label summarizes a review of 150 overdoses: patients who ingested less than 0.5 mg/kg survived, mostly with gastrointestinal toxicity; 0.5 to 0.8 mg/kg caused severe toxicity with myelosuppression; and mortality was 100% above 0.8 mg/kg. Deaths have occurred after as little as 7 mg taken over 4 days. The LODOCO label states that acute overdose above 0.5 mg/kg (35 mg in a 70-kg adult) is usually fatal.

Phases of acute colchicine toxicity, from the COLCRYS prescribing information.

There is no antidote. Treatment is supportive: activated charcoal for recent ingestion, fluid and vasopressor support, ventilation, management of arrhythmia, granulocyte colony-stimulating factor for marrow failure, and treatment of infection. Hemodialysis does not remove colchicine, because of its large volume of distribution, although it may be needed for kidney failure. Cardiac involvement includes myocardial depression and cardiogenic shock, and survival of severe poisoning depends on early intensive care. Regional poison control centers are involved early. Chronic toxicity from accumulation presents more slowly, with diarrhea, weakness, neuromyopathy, and cytopenias, and is managed by stopping colchicine and removing the interacting drug.

Pregnancy, lactation, and fertility

Colchicine crosses the placenta, and fetal plasma levels are about 15% of maternal levels. Animal studies show embryofetal toxicity. Decades of human data, mainly from women with FMF who continue colchicine through pregnancy, have not shown an increase in major birth defects, miscarriage, or stillbirth, and the LODOCO label summarizes these data. Colchicine was considered contraindicated in pregnancy in the 2015 ESC pericardial guideline, and the 2025 ESC guideline allows it for prevention of recurrent pericarditis in pregnancy (Class 2b). For cardiovascular prevention, the trials did not enroll pregnant women, and the drug is generally stopped in pregnancy, when the absolute short-term risk of atherosclerotic events is low.

Colchicine is present in breast milk. A systematic review found no adverse effects in 149 breastfed children, and a prospective cohort found no gastrointestinal or other symptoms in 38 exposed infants. Infertility in men is rare and reversible, with case reports of azoospermia that resolved after colchicine was stopped. No clear effect on female fertility has been established. Management of pericarditis in pregnancy is covered on the Acute and recurrent pericarditis page.

Familial Mediterranean fever and gout: noncardiac uses that cardiologists encounter

Gout. Gout is common in patients with coronary disease, chronic kidney disease, and heart failure, and loop and thiazide diuretics raise uric acid. Colchicine is used for treatment of flares and for prophylaxis during the first months of urate-lowering therapy. A patient already taking colchicine 0.5 mg daily for cardiovascular prevention who has a flare is not given the full flare regimen on top of it without considering kidney function and interacting drugs. The COLCRYS label advises against flare treatment in patients with renal or hepatic impairment who already take colchicine prophylaxis. NSAIDs used for gout flares in patients with heart failure or kidney disease cause fluid retention and kidney injury, which makes colchicine or a short course of corticosteroids the usual alternative in cardiology patients. Observational studies in gout found fewer myocardial infarctions among colchicine users, which contributed to the cardiovascular hypothesis.

Familial Mediterranean fever. FMF is an autosomal recessive autoinflammatory disease caused by mutations in MEFV, which encodes pyrin. Attacks combine fever with serositis, including peritonitis, pleuritis, and pericarditis. Lifelong colchicine at 1.2 to 2.4 mg daily prevents attacks and AA amyloidosis, which otherwise causes nephrotic syndrome and kidney failure. FMF and other periodic fever syndromes are considered in patients with recurrent pericarditis with fever, high CRP, and polyserositis. Pericarditis in autoinflammatory disease is discussed on the Acute and recurrent pericarditis page.

Other inflammatory conditions. Colchicine is used in Behçet disease, calcium pyrophosphate deposition disease, and some neutrophilic dermatoses. In COVID-19, colchicine did not reduce mortality in large hospital trials and is not used for that purpose.

Canakinumab and CANTOS: proof of the inflammatory hypothesis

CANTOS was the first trial to test inflammation inhibition without lipid lowering. It randomized 10,061 patients with prior myocardial infarction and hsCRP of 2 mg/L or more to canakinumab, a monoclonal antibody against IL-1β, at 50, 150, or 300 mg subcutaneously every 3 months, or placebo. Canakinumab did not change LDL-C. It lowered hsCRP in a dose-dependent manner, by 26, 37, and 41 percentage points more than placebo at 48 months.

Over a median of 3.7 years, the primary endpoint of nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death occurred at 4.50 events per 100 person-years with placebo and 3.86 with canakinumab 150 mg (hazard ratio 0.85, 95% confidence interval 0.74 to 0.98). The 150-mg dose was the only dose that met the multiplicity-adjusted threshold for the primary endpoint and for the secondary endpoint that added urgent revascularization for unstable angina (hazard ratio 0.83). All-cause mortality did not differ (hazard ratio 0.94 for all doses combined). Fatal infection and sepsis were more frequent with canakinumab, and neutropenia and thrombocytopenia occurred. Cancer mortality, particularly from lung cancer, was lower, an exploratory finding.

In a prespecified secondary analysis, patients who achieved an on-treatment hsCRP below 2 mg/L after the first dose had a 25% reduction in major adverse cardiovascular events (adjusted hazard ratio 0.75), with lower cardiovascular and all-cause mortality. Those whose hsCRP remained at 2 mg/L or more had no significant benefit (hazard ratio 0.90). The analysis was not randomized by response, but it linked the magnitude of inflammation reduction to benefit.

CANTOS established that inhibiting IL-1β reduces atherothrombotic events independently of lipids. Canakinumab was not approved for cardiovascular use. The FDA issued a complete response letter in October 2018. Novartis withdrew its European application in December 2018, when the European Medicines Agency's committee judged the benefit modest and insufficient to outweigh the increased risk of serious infections. Canakinumab is approved for periodic fever syndromes and other rare autoinflammatory diseases.

Methotrexate and other anti-inflammatory strategies that failed

Neutral and negative trials of anti-inflammatory therapy in atherosclerotic disease. MI indicates myocardial infarction; HR, hazard ratio.

CIRT, run by the CANTOS investigators, tested whether general immunosuppression lowers cardiovascular events. Methotrexate, an effective drug in rheumatoid arthritis, did not lower IL-1β, IL-6, or CRP in patients with atherosclerosis and did not reduce events. These results indicate that benefit requires inhibition of the specific NLRP3, IL-1β, and IL-6 pathway and not general immunosuppression. Corticosteroids, NSAIDs other than aspirin, and cyclooxygenase-2 inhibitors are not cardioprotective, and NSAIDs increase cardiovascular risk.

IL-6 inhibition: ziltivekimab and tocilizumab

IL-6 is downstream of IL-1β and upstream of CRP, and human genetic data implicate IL-6 receptor signaling causally in coronary disease. Ziltivekimab is a fully human monoclonal antibody against the IL-6 ligand, given subcutaneously once a month. In the phase 2 RESCUE trial of 264 patients with moderate to severe chronic kidney disease and hsCRP of at least 2 mg/L, ziltivekimab 7.5, 15, and 30 mg lowered hsCRP at 12 weeks by a median of 77%, 88%, and 92%, compared with 4% with placebo. Fibrinogen, serum amyloid A, and lipoprotein(a) were also reduced.

ZEUS was the cardiovascular outcome trial. It randomized more than 6,300 patients with atherosclerotic disease, chronic kidney disease, and hsCRP of 2 mg/L or more to ziltivekimab 15 mg monthly or placebo. In topline results, ziltivekimab lowered free IL-6 and hsCRP as expected but did not reduce major adverse cardiovascular events (hazard ratio 0.99, 95% confidence interval 0.88 to 1.11). Serious infections were more frequent, and all-cause mortality did not differ. ZEUS shows that large reductions in hsCRP through IL-6 inhibition do not necessarily translate into fewer events, a finding that parallels CLEAR SYNERGY. ARTEMIS, a trial in acute myocardial infarction, is ongoing.

Tocilizumab, an antibody against the IL-6 receptor approved for rheumatoid arthritis and giant cell arteritis, was tested at the time of reperfusion. In ASSAIL-MI, a single 280-mg infusion in 199 patients with STEMI within 6 hours of symptom onset increased the myocardial salvage index on cardiac magnetic resonance at 3 to 7 days (adjusted difference 5.6 percentage points) and reduced microvascular obstruction, but final infarct size did not differ significantly. IL-6 inhibition remains investigational in cardiovascular disease, and IL-6 inhibitors raise LDL-C and triglycerides and increase infection risk.

IL-1 blockade in recurrent pericarditis

In pericarditis, the IL-1 pathway is the established therapeutic target. Recurrent pericarditis with an inflammatory phenotype (fever, elevated CRP, effusion, or pericardial late gadolinium enhancement) is an autoinflammatory disease driven by IL-1α and IL-1β. Rilonacept, a soluble receptor fusion protein that binds IL-1α and IL-1β, reduced recurrence in the randomized-withdrawal phase of RHAPSODY from 74% with placebo to 7% (hazard ratio 0.04) and was approved by the FDA for recurrent pericarditis in 2021. Anakinra, an IL-1 receptor antagonist, is used off-label with randomized evidence from AIRTRIP. The 2025 ACC guidance places IL-1 blockade after failure of, or intolerance to, aspirin or an NSAID with colchicine in patients with the inflammatory phenotype, without requiring a corticosteroid trial first. Agents, trials, duration, and withdrawal are covered on the Acute and recurrent pericarditis page.

Colchicine with lipid lowering, SGLT2 inhibitors, and GLP-1 receptor agonists

Residual risk after an atherosclerotic event has several components that are addressed in parallel: LDL-C and lipoprotein(a), triglyceride-rich lipoproteins, blood pressure, diabetes and kidney disease, obesity, thrombosis, and inflammation. Colchicine addresses only the last, and its trials were conducted on a background of statins and antiplatelet therapy. In LoDoCo2, nearly all patients received statins and most received antiplatelet drugs. LDL-C is lowered to goal first, according to the LDL-lowering guidelines, because LDL lowering has the larger and more certain effect on events and on mortality.

Some cardiometabolic drugs also lower inflammatory markers. Statins, GLP-1 receptor agonists, and weight loss reduce hsCRP, and sodium-glucose cotransporter 2 (SGLT2) inhibitors have anti-inflammatory effects in experimental models. None of the colchicine trials enrolled many patients taking these newer drugs, so the incremental benefit of colchicine on top of them is unknown. No pharmacokinetic interaction exists between colchicine and SGLT2 inhibitors, GLP-1 receptor agonists, ezetimibe, proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors, bempedoic acid, or P2Y12 inhibitors, apart from possible P-glycoprotein effects of ticagrelor. No dose adjustment is needed when colchicine is combined with them.

Sources of error in prescribing colchicine

• Prescribing colchicine with clarithromycin, an azole antifungal, ritonavir, or cyclosporine. These combinations cause fatal toxicity at ordinary doses, especially with kidney or liver impairment; colchicine is held or the other drug is replaced.
• Adding colchicine to diltiazem or verapamil in a patient with reduced kidney function. The LODOCO label advises against a moderate CYP3A4 inhibitor with renal or hepatic impairment, and neuromyopathy has been reported with both drugs.
• Giving cardiovascular-dose colchicine at a creatinine clearance below 15 mL/min or on dialysis. Both are contraindications, and dialysis does not remove the drug.
• Using estimated glomerular filtration rate indexed to body surface area in a small older patient. The labels use Cockcroft-Gault creatinine clearance, which is often lower.
• Starting colchicine in the first days after myocardial infarction on the basis of COLCOT. CLEAR SYNERGY, the largest trial of early initiation, was neutral, and the guideline recommendation applies to stable patients.
• Using colchicine in place of LDL lowering. Colchicine is an adjunct; it does not lower LDL-C and has not reduced mortality.
• Requiring an elevated hsCRP before colchicine is prescribed. The coronary outcome trials that showed benefit did not select patients by hsCRP, and no US guideline makes it a condition of therapy.
• Measuring hsCRP during an intercurrent illness. A value above 10 mg/L reflects an acute process, and the test is repeated after recovery.
• Attributing muscle weakness in a patient taking colchicine and a statin to the statin alone. Colchicine neuromyopathy presents with proximal weakness and a raised creatine kinase, especially with declining kidney function or a new interacting drug.
• Treating new diarrhea or vomiting as a benign side effect in a patient at risk of accumulation. Gastrointestinal symptoms are the first stage of toxicity.
• Adding a full gout-flare regimen to cardiovascular colchicine without regard to kidney function. The combined dose and accumulation increase the risk of toxicity.
• Using the cardiovascular dose for pericarditis or omitting colchicine in pericarditis. Pericarditis requires weight-based dosing for 3 months after a first episode and 6 to 12 months after a recurrence, and omission of colchicine roughly doubles the risk of recurrence.

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