Does colchicine, an old gout drug, prevent heart attacks?

Colchicine, a cheap anti-inflammatory drug used for gout and pericarditis for decades, was found in two randomised trials to lower the rate of cardiovascular events in people with coronary disease, and on that evidence the US Food and Drug Administration approved a low-dose version to reduce heart risk in June 2023 [s1] [s2] [s4]. But the largest and most recent trial, reported in late 2024, found no benefit at all — so the honest answer is that whether colchicine prevents heart attacks is, after more than 12,000 randomised patients, still unresolved [s3].

Why an inflammation drug was tried on the heart

Atherosclerosis is not only a plumbing problem of cholesterol and narrowing; inflammation inside the artery wall drives the plaques that rupture and cause heart attacks and strokes. Colchicine is a potent, orally administered anti-inflammatory that is long established for gout and pericarditis, which made it an obvious candidate to test against cardiovascular events [s1]. The appeal is partly economic: it is generic and inexpensive, unlike the newer injectable anti-inflammatory antibodies that were tried on the same idea.

The two trials that built the case

COLCOT, published in the New England Journal of Medicine in 2019, enrolled 4,745 patients within 30 days of a heart attack and assigned them to colchicine 0.5 mg once daily or placebo [s1]. Over a median of 22.6 months, the primary composite endpoint — cardiovascular death, resuscitated cardiac arrest, heart attack, stroke, or urgent hospitalisation for angina leading to revascularisation — occurred in 5.5% of the colchicine group versus 7.1% of the placebo group, a hazard ratio of 0.77 (95% confidence interval, 0.61 to 0.96; P = 0.02) [s1]. The effect was driven heavily by fewer strokes (hazard ratio 0.26; 95% CI, 0.10 to 0.70) and fewer urgent revascularisations [s1].

LoDoCo2 extended the question to stable, longer-standing disease. Published in 2020, it randomised 5,522 patients with chronic coronary disease to the same 0.5 mg daily dose or placebo and followed them a median of 28.6 months [s2]. A primary-endpoint event occurred in 6.8% of the colchicine group and 9.6% of the placebo group (hazard ratio 0.69; 95% CI, 0.57 to 0.83; P < 0.001) [s2]. One number in that trial was a warning sign the headline result tends to bury: deaths from non-cardiovascular causes were higher with colchicine (hazard ratio 1.51; 95% CI, 0.99 to 2.31), a difference that did not reach significance but has kept appearing in the debate [s2].

Those two trials were enough for regulators. In June 2023 the FDA approved Lodoco, colchicine at 0.5 mg, to reduce the risk of cardiovascular events in adults with established atherosclerotic disease or multiple risk factors — an anti-inflammatory drug cleared to lower heart risk rather than to treat gout [s4].

The trial that undercut it

Then came CLEAR SYNERGY, also known as OASIS-9, the largest test yet. Reported in the New England Journal of Medicine after being presented in late 2024, it randomised 7,062 patients at 104 centres in 14 countries after a heart attack to colchicine or placebo [s3]. Over a median of three years, a primary-endpoint event occurred in 9.1% of the colchicine group and 9.3% of the placebo group — a hazard ratio of 0.99 (95% CI, 0.85 to 1.16; P = 0.93), which is as flat a null result as trials produce [s3].

Crucially, the null was not because the drug did nothing biologically. Colchicine still lowered C-reactive protein, a marker of inflammation, by about 1.28 mg per litre at three months versus placebo (95% CI, 0.75 to 1.81) — it hit its inflammatory target but did not move the clinical outcome [s3]. Diarrhoea was more common with colchicine (10.2% versus 6.6%; P < 0.001), the drug's characteristic side effect [s3].

What the discrepancy means

Three good trials pointing in two directions is uncomfortable, and there is no fully agreed explanation. CLEAR SYNERGY was larger and more recent, its patients were treated with modern background therapy — high-intensity statins, potent antiplatelets — that leaves less room for an added drug to show benefit, and it started colchicine soon after the heart attack. Whether the earlier positive trials caught a real effect that better baseline care has now erased, or whether they overstated a benefit that the bigger trial has corrected, is exactly the kind of question a single study cannot settle.

For readers the practical picture is unsettled rather than negative. Colchicine is approved and inexpensive, and clinicians who were persuaded by COLCOT and LoDoCo2 have a regulatory basis to use it; those who weight the largest trial most heavily now have strong grounds to doubt it [s1] [s2] [s3] [s4]. This is not a supplement with a marketing story — it is a real drug with real trials that disagree, and the disagreement is the news. As related questions about whether targeting inflammation changes heart outcomes continue to be tested, colchicine is likely to remain a case study in why one positive trial, or even two, is not the end of the argument.