Low-dose colchicine

Short answer

Low-dose colchicine (0.5 mg a day, sold as Lodoco) was FDA-approved in 2023 to lower cardiovascular risk in people with atherosclerotic disease. A 2025 Cochrane review rates the evidence high-certainty for about a quarter fewer heart attacks and a third fewer strokes in people who already have heart disease, with more stomach and gut side effects and no change in cardiovascular or all-cause death. The largest trial started right after a heart attack (CLEAR SYNERGY, 7,062 patients) was null. Evidence in healthy people is very low certainty, and no trial has tested it for aging.

Summary drafted from this entry’s sources; editorial review pending.

01Key questions

Does low-dose colchicine reduce deaths?

No. The 2025 Cochrane review of 12 secondary-prevention trials found no difference in all-cause mortality (risk ratio 1.01) or cardiovascular mortality (0.94). The "31% lower risk" figure from LoDoCo2 is for a composite of cardiovascular events, not death.³¹

Who benefits from colchicine?

People with established coronary disease or stroke. Pooled trials show fewer heart attacks (risk ratio 0.74) and strokes (0.67). Benefit in LoDoCo2 held across lower- and higher-risk patients.³¹²

Why was CLEAR SYNERGY null?

In 7,062 patients started on colchicine after a heart attack, events were 9.1% versus 9.3% over three years, even though C-reactive protein fell. CLEAR was null, while COLCOT found fewer composite events in patients enrolled within 30 days of myocardial infarction. Timing alone does not explain the difference.⁷

Should healthy people take colchicine for inflammaging?

There is no evidence for it. The Cochrane primary-prevention review rates all outcomes very low certainty, and many of its trials were in liver disease. Colchicine also has a narrow therapeutic index and interacts with common drugs that block CYP3A4 or P-glycoprotein.⁴

What are the side effects?

Gut side effects are the consistent harm (Cochrane risk ratio 1.68; diarrhea 10.2% versus 6.6% in CLEAR SYNERGY). COLCOT saw slightly more pneumonia, which later pooled analyses did not confirm.³⁷²

Low-dose colchicine is the first drug approved specifically to treat residual inflammatory risk in atherosclerotic disease. It is not a longevity supplement. The defensible claim, as of the November 2025 Cochrane review, is fewer myocardial infarctions and strokes in people who already have cardiovascular disease, with more gastrointestinal events and no demonstrated mortality benefit. A 2025 acute-myocardial-infarction trial of 7,062 patients was null. Marketing that collapses those results into "anti-aging" or "31% fewer deaths" is not what the trials measured.

Colchicine is the clearest clinical test so far of chronic inflammation ("inflammaging"), one of the hallmarks of aging. It is a drug for vascular events, closer to SGLT2 inhibitors (a repurposed drug with hard outcomes) than to metformin and rapamycin (aging-biology candidates without this kind of cardiovascular approval).

Not medical advice. Colchicine has a narrow therapeutic index: the gap between an effective and a toxic dose is small.

02Separate claims that get collapsed

Claim	Evidence class	Status
—	Double-blind RCT, n=5,522, median 28.6 months	Supported (PMID 32865380)
—	Double-blind RCT, n=4,745, median 22.6 months	Supported, driven by stroke and urgent revascularization, not by myocardial infarction itself (PMID 31733140)
Colchicine reduces all-cause or cardiovascular death in secondary prevention	Cochrane 2025, moderate certainty	Not shown (PMID 41224205)
Colchicine prevents first cardiovascular events in people without disease	Cochrane 2025, very low certainty; many included trials were in liver disease	Inconclusive (PMID 39927511)
The benefit is "plaque cooling" visible as less pericoronary fat inflammation	Cross-sectional CT substudy, n=151	Not shown; fat attenuation did not differ (PMID 40393691)
This extends lifespan or slows biological aging	No such trial	Unsupported

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03Human evidence

LoDoCo (2013): small, observer-blinded, optimistic

PMID 23265346. Prospective, randomized, observer-blinded endpoint trial. 532 patients with stable coronary disease, 93% on aspirin and/or clopidogrel, 95% on a statin. Colchicine 0.5 mg/day versus no colchicine. Median follow-up 3 years.

Primary outcome (acute coronary syndrome, out-of-hospital cardiac arrest, or noncardioembolic ischemic stroke): 15/282 (5.3%) versus 40/250 (16.0%). Hazard ratio 0.33 (95% CI 0.18–0.59), P<0.001. Number needed to treat 11.
32 patients (11%) assigned to colchicine withdrew within 30 days for intestinal intolerance.
On-treatment analysis, after those withdrawals plus 7 who never started, was even larger (4.5% versus 16.0%; HR 0.29, 95% CI 0.15–0.56).

This is the trial that made the hypothesis look dramatic. It was not double-blind, and the control arm event rate (16%) is high relative to later trials. Treat it as hypothesis-generating relative to LoDoCo2, not as the effect size to quote.

The authors' stated mechanism in that paper: activated neutrophils in unstable plaques, and the possibility that inhibiting neutrophil function reduces plaque instability. That is a rationale, not a demonstration that neutrophils were the operative target in the patients.

COLCOT (2019): recent myocardial infarction

Tardif et al., New England Journal of Medicine (PMID 31733140). Randomized, double-blind. Patients recruited within 30 days after a myocardial infarction. Colchicine 0.5 mg once daily versus placebo. 4,745 patients (2,366 colchicine, 2,379 placebo). Median follow-up 22.6 months.

Primary endpoint: cardiovascular death, resuscitated cardiac arrest, myocardial infarction, stroke, or urgent hospitalization for angina leading to revascularization.

5.5% versus 7.1%. Hazard ratio 0.77 (95% CI 0.61–0.96), P=0.02.
Component hazard ratios: cardiovascular death 0.84 (0.46–1.52); resuscitated cardiac arrest 0.83 (0.25–2.73); myocardial infarction 0.91 (0.68–1.21); stroke 0.26 (0.10–0.70); urgent angina hospitalization leading to revascularization 0.50 (0.31–0.81).
Diarrhea 9.7% versus 8.9% (P=0.35).
Pneumonia as a serious adverse event 0.9% versus 0.4% (P=0.03).

The composite win was not a myocardial-infarction win. Stroke and urgent revascularization carried it. The pneumonia signal is small in absolute terms and was not reproduced as an increase in serious infections in CLEAR SYNERGY or as pneumonia hospitalization in the 2025 European Heart Journal meta-analysis below.

LoDoCo2 (2020): chronic coronary disease, the pivotal trial

Nidorf et al., New England Journal of Medicine (PMID 32865380). Randomized, controlled, double-blind. Chronic coronary disease. Colchicine 0.5 mg once daily versus matching placebo. 5,522 patients (2,762 colchicine, 2,760 placebo). Median follow-up 28.6 months.

Primary endpoint (cardiovascular death, spontaneous myocardial infarction, ischemic stroke, or ischemia-driven coronary revascularization): 187 (6.8%) versus 264 (9.6%). Incidence 2.5 versus 3.6 events per 100 person-years. Hazard ratio 0.69 (95% CI 0.57–0.83), P<0.001.
Key secondary (cardiovascular death, spontaneous myocardial infarction, or ischemic stroke): 115 (4.2%) versus 157 (5.7%). Hazard ratio 0.72 (95% CI 0.57–0.92), P=0.007.
Death from noncardiovascular causes was higher with colchicine: 0.7 versus 0.5 events per 100 person-years. Hazard ratio 1.51 (95% CI 0.99–2.31). The interval includes 1. It is a signal, not a demonstrated harm, and later pooled analyses have not confirmed an increase in non-cardiovascular death (see below).

The sponsor's "31% lower risk" figure is this primary hazard ratio (1 − 0.69), applied to a composite of cardiovascular events. It is not a mortality reduction.

The FDA clinical review of NDA 215727 treated LoDoCo2 as the single pivotal trial, with LoDoCo as confirmatory evidence, and concluded the benefit-risk favored approval for reducing cardiovascular death, myocardial infarction, stroke, or coronary revascularization.

CLEAR SYNERGY (2025): the null acute-infarction trial

New England Journal of Medicine (PMID 39555823; design paper PMID 38936755). Multicenter 2×2 factorial trial of colchicine versus placebo and spironolactone versus placebo after myocardial infarction. 7,062 patients at 104 centers in 14 countries. Median follow-up 3 years. Vital status unknown for 45 patients (0.6%).

Primary outcome (cardiovascular death, recurrent myocardial infarction, stroke, or unplanned ischemia-driven coronary revascularization): 322/3,528 (9.1%) versus 327/3,534 (9.3%). Hazard ratio 0.99 (95% CI 0.85–1.16), P=0.93.
Individual components appeared similar.
Diarrhea 10.2% versus 6.6% (P<0.001). Serious infections did not differ.

The spironolactone half of the same factorial was also null on both of its primary outcomes (PMID 39555814). That paper is out of scope here except as a reminder that the platform was large enough to detect a moderate effect and did not.

A 2025 commentary in Nature Cardiovascular Research discusses implications and limitations of CLEAR SYNERGY for low-dose colchicine. The facts are stark enough on their own: CRP fell, events did not, in the largest acute-myocardial-infarction test.

2025 syntheses: what survives after the null trial

Two European Heart Journal meta-analyses and one Cochrane review landed in 2025. They do not agree on every endpoint because they do not ask the same question.

d'Entremont et al., fixed-effect, secondary prevention (PMID 40314334). Nine trials, 30,659 patients (15,255 colchicine, 15,404 control) with known coronary disease or stroke. Primary outcome: cardiovascular death, myocardial infarction, or stroke.

Relative risk 0.88 (95% CI 0.81–0.95), P=0.002. A 12% relative reduction on that composite.
Cardiovascular death 0.94 (0.78–1.13), P=0.5.
Myocardial infarction 0.84 (0.73–0.97), P=0.016.
Stroke 0.90 (0.80–1.02), P=0.09.
Hospitalization for gastrointestinal events 1.35 (1.10–1.66), P=0.004.
No increase in hospitalization for pneumonia, newly diagnosed cancers, or non-cardiovascular death.

Longer-term trial pool (PMID 40314333). Six RCTs with at least 12 months of follow-up, 21,800 patients (10,871 colchicine, 10,929 placebo), follow-up 12–34 months. Major adverse cardiovascular events (cardiovascular mortality, myocardial infarction, ischemic stroke, urgent coronary revascularization): pooled hazard ratio 0.75 (95% CI 0.56–0.93). The interval is wide. Non-cardiovascular death risk ratio 1.08 (95% CI 0.76–1.54).

Cochrane, secondary prevention, search to February 2025 (Ebrahimi et al., PMID 41224205). 12 studies, 22,983 randomized participants. Follow-up 6–80 months. Doses were 0.5 mg once or twice daily. Mean age 57–74 years. 79.4% male.

Myocardial infarction: high-certainty evidence, risk ratio 0.74 (95% CI 0.57–0.96; 22,153 participants, 8 studies; I²=51%). Absolute reduction about 9 fewer events per 1,000 (95% CI 16 fewer to 2 fewer) when the control rate is about 4%.
Stroke: high-certainty evidence, risk ratio 0.67 (95% CI 0.47–0.95; 22,483 participants, 10 studies; I²=40%). About 8 fewer per 1,000 (12 fewer to 1 fewer) when the control rate is about 2%.
Serious adverse events: risk ratio 0.98 (95% CI 0.94–1.02; 15,677 participants, 4 studies; I²=0%).
Gastrointestinal adverse events: risk ratio 1.68 (95% CI 1.11–2.57; 22,185 participants, 10 studies; I²=91%). Described as typically mild and transient. The heterogeneity is large.
All-cause mortality: moderate certainty, risk ratio 1.01 (95% CI 0.84–1.21).
Cardiovascular mortality: moderate certainty, risk ratio 0.94 (95% CI 0.73–1.22).
Coronary revascularization: moderate certainty, risk ratio 0.83 (95% CI 0.64–1.08).
No evidence on quality of life or all-cause hospitalization.

The review authors explicitly say more work is needed on long-term use in stable coronary disease versus limited-time use after acute coronary syndrome. COLCOT also found benefit after recent myocardial infarction, so timing alone does not explain the conflicting results.

Primary prevention: do not extrapolate

Cochrane, primary prevention (PMID 39927511; search updated 31 May 2023). 15 RCTs, 1,721 randomized, 1,412 analyzed. Follow-up 4–728 weeks. All but one trial at high risk of bias. Many included trials were in liver disease, not in a general cardiovascular-risk population. All outcomes very low certainty.

All-cause mortality versus placebo: risk ratio 0.68 (95% CI 0.51–0.91; 6 studies, 463 participants). Number needed to treat 11 (95% CI 6–67). The review's own grade is very low certainty.
Non-fatal myocardial infarction: risk ratio 0.87 (0.41–1.82; 1 study, 100 participants).
Stroke: risk ratio 2.43 (0.67–8.86; 1 study, 100 participants).

The authors' conclusion: existing evidence on cardiovascular benefits or harms for primary prevention is inconclusive. A healthy person adding colchicine to "lower inflammaging" is outside every trial that actually supports the drug.

Mechanism checks that failed to match the slogan

Fiolet et al., Heart 2025 (PMID 40393691). Cross-sectional CT substudy of LoDoCo2. 151 participants imaged after a median 28.2 months of assigned treatment.

Pericoronary adipose-tissue attenuation did not differ: median −79.5 HU (colchicine) versus −78.7 HU (placebo), P=0.236.
Colchicine was associated with higher calcified-plaque volume (169.6 versus 113.1 mm³, P=0.041) and burden (9.6% versus 7.0%, P=0.035), and higher dense-calcified volume (192.8 versus 144.3 mm³, P=0.048), independent of statin therapy.
Lower low-attenuation plaque burden was seen only in the low-intensity statin stratum (interaction P=0.037), not in high-intensity statin users.

Dense calcification is sometimes read as a stability marker. That reading is an interpretation. The measurement that would have supported "less pericoronary inflammation" did not move.

Who benefits: not only the highest-risk stratum

Mohammadnia et al., Journal of the American Heart Association 2025 (PMID 40371626). Secondary analysis of LoDoCo2. A trial-derived risk score flagged age ≥75, diabetes, and current smoking. Relative hazard ratios were 0.72 (95% CI 0.56–0.94) in patients with at least one of those features and 0.67 (0.52–0.88) with none (interaction P=0.73). Absolute reductions were −1.33 versus −0.93 events per 100 person-years. A second score (TIMI Risk Score for Secondary Prevention) gave the same pattern across high, intermediate, and low risk. Guideline language that reserves colchicine for "selected high-risk patients" is narrower than this secondary analysis. It is still a secondary analysis of one trial, not a new indication.

04Regulatory status

Lodoco (colchicine tablets, 0.5 mg; AGEPHA Pharma) was FDA-approved in June 2023 to reduce the risk of myocardial infarction, stroke, coronary revascularization, and cardiovascular death in adults with established atherosclerotic disease or with multiple risk factors for cardiovascular disease. The approval history page lists 16 June 2023 as the first-approval date and 20 June 2023 as the announcement. NDA 215727. Priority review. The labeled dose matches the trial dose (0.5 mg daily).

This approval does not make colchicine an anti-aging drug. The indication is atherosclerotic risk reduction. Gout and pericarditis are older indications, stated as such in the COLCOT paper.

A 2025 clinical review notes that cytochrome P450 and P-glycoprotein inhibitors share metabolic pathways with colchicine. Interaction risk is the reason colchicine is a poor candidate for casual stacking.

05What this is not

Not a primary-prevention longevity intervention. The Cochrane primary-prevention review is very low certainty and contaminated by liver-disease trials.
Not a mortality drug. The best secondary-prevention synthesis shows fewer infarctions and strokes and no mortality difference.
Not proven in the acute-infarction window that CLEAR SYNERGY tested.
Not evidence that "inflammaging" as a systemic aging process has been treated. The outcomes are vascular events in people with vascular disease.
Not interchangeable with canakinumab or other anti-inflammatory cardiovascular trials.

06Practical context

The trial doses are listed under "What studies and practitioners report". In the 2013 LoDoCo trial, 11% of the colchicine arm stopped within 30 days because of gut intolerance.

Harms that are actually quantified:

Gastrointestinal events are the consistent harm (Cochrane risk ratio 1.68; d'Entremont hospitalization risk ratio 1.35; CLEAR diarrhea 10.2% versus 6.6%).
COLCOT pneumonia serious adverse events 0.9% versus 0.4%. Not confirmed as a pneumonia-hospitalization increase in the 2025 nine-trial meta-analysis, and serious infections did not differ in CLEAR SYNERGY.
LoDoCo2 noncardiovascular death hazard ratio 1.51 (0.99–2.31). Later pools do not show a significant increase. It is a signal worth watching, not an established harm.
Narrow therapeutic index and CYP / P-glycoprotein interactions are the safety reason this does not belong in an unsupervised stack.

No aging clock, function, or lifespan endpoint has been reported for this dose.

07What to watch

LoDoCo2 was positive in stable disease; COLCOT and CLEAR SYNERGY gave conflicting results after recent myocardial infarction. The trial that would settle it compares stable disease with the acute setting in a pre-specified way.
Plaque imaging did not confirm the pericoronary-inflammation story. A serial-imaging study (not cross-sectional) showing a plaque change that tracks events would change that.
Primary-prevention evidence would have to be a cardiovascular-risk trial, not another liver-disease colchicine series folded into a Cochrane average.
Noncardiovascular death in LoDoCo2 still lacks a satisfying explanation (play of chance, competing risk, infection, or something else). The confidence interval includes no effect, so it remains open.

08Who paid, and how it got here

Who funded the key studies on this page, the favourable and the unfavourable alike, and how its legal status came about. From each paper’s funding and conflict-of-interest statements, trial registries and official documents; checked 1 Nov 2026. Why we show this

How it got here

FDA approved Lodoco for cardiovascular risk reduction on 16 June 2023. AGEPHA submitted a 505(b)(2) application relying on published LoDoCo2 results and a scientific bridge to Colcrys. FDA approval list FDA multidisciplinary review, NDA 215727

Who paid for the key studies

LoDoCo2 2025 risk analysis of randomized trial, n=5,522Benefits extended across baseline cardiovascular risk groups.Funding and interests: Australian and Dutch public/charitable support, plus Teva, Disphar and Tiofarma. Paper's funding statement
LoDoCo2 2025 risk analysis, author interests, n=5,522Benefits extended across baseline cardiovascular risk groups.Funding and interests: Mosterd: Tiofarma, TEVA and Novartis advisory/consulting roles; fees donated to research. Conflict-of-interest statement
CLEAR SYNERGY, factorial randomized trial, n=7,062CRP fell; cardiovascular events did not.Funding and interests: Boston Scientific, PHRI, CIHR and Accelerating Clinical Trials consortium; Tiofarma supplied discounted study drugs. Paper's funding statement
COLCOT, randomized placebo-controlled trial, n=4,745Fewer composite cardiovascular events after recent myocardial infarction.Funding and interests: Montreal Heart Institute (registered sponsor). Trial registry
Cochrane 2025 secondary-prevention review, 12 trials, n=22,983Fewer heart attacks and strokes; no demonstrated mortality reduction.Funding and interests: Author FE: Boehringer Ingelheim advisory role and Gilead travel support. Conflict-of-interest statement

What studies and practitioners report

Amounts as reported in the cited sources: trial doses with the population studied, and practitioner-reported ranges marked as such. Not medical advice.

Trial 0.5 mg/day colchicine, oral · median 28.6 months; also the Lodoco label dose adults with chronic coronary disease, n=5,522 PMID 32865380
Trial 0.5 mg/day colchicine, oral · started within 30 days of a heart attack, median 22.6 months adults after myocardial infarction, n=4,745 PMID 31733140
Trial 0.5 mg once or twice daily · range across pooled trials, 6 to 80 months 12 secondary-prevention trials, 22,983 participants PMID 41224205

09Connections

Neighborhood · 6 linked entriesOpen full map →

10Sources

LoDoCo2, NEJM 2020: PMID 32865380PubMed 32865380
COLCOT, NEJM 2019: PMID 31733140PubMed 31733140
Cochrane secondary prevention, 13 Nov 2025: PMID 41224205PubMed 41224205
Cochrane primary prevention, 2025: PMID 39927511PubMed 39927511
LoDoCo2 CT plaque substudy, Heart 2025: PMID 40393691PubMed 40393691
LoDoCo, observer-blinded, 2013: PMID 23265346PubMed 23265346
CLEAR SYNERGY colchicine results, NEJM 2025: PMID 39555823PubMed 39555823
CLEAR design: PMID 38936755PubMed 38936755
PubMed 39555814PubMed 39555814
d'Entremont meta-analysis, Eur Heart J 2025: PMID 40314334PubMed 40314334
Long-term trial meta-analysis, Eur Heart J 2025: PMID 40314333PubMed 40314333
LoDoCo2 risk-stratum analysis, JAHA 2025: PMID 40371626PubMed 40371626

11Entry history

1 Nov 2026