Gout drug repurposed to fight heart disease
LoDoCo2 trial presented in a Hot Line Session today at ESC Congress 2020
Sophia Antipolis, France – 31 Aug 2020: Colchicine reduces the risk of major cardiovascular events in patients with chronic coronary disease, according to results of the LoDoCo2 trial presented in a Hot Line session today at ESC Congress 2020.1
“Over a decade, more than one in three heart patients will have another heart attack or stroke, or die from heart disease, despite taking preventive medication,” said study author Dr. Mark Nidorf of GenesisCare, Australia. “Our study shows that this could be reduced to one in four with the addition of low-dose colchicine.”
Colchicine, originally derived from the bulb of the crocus plant, has been used since ancient times to treat inflammation. Now synthetically made, it is a generic medication taken to treat gout. The drug also inhibits several inflammatory pathways known to be important in atherosclerosis. The LoDoCo (Low Dose Colchicine) pilot trial suggested that colchicine 0.5 mg once daily was safe and effective for preventing cardiovascular events in patients with coronary artery disease.
The LoDoCo2 trial randomised 5,552 patients who had chronic coronary disease, and were tolerant to colchicine during a 30-day open-label run-in phase, to colchicine 0.5 mg daily or matching placebo on a background of lipid lowering and antithrombotic therapy.2,3 The primary endpoint was a composite of cardiovascular death, myocardial infarction, ischaemic stroke, or ischaemia-driven coronary revascularisation.
During a median follow-up of almost 30 months, the primary endpoint occurred in 187 (6.8%) patients in the colchicine group and 264 (9.6%) patients in the placebo group (hazard ratio [HR] 0.69; 95% confidence interval [CI] 0.57-0.83; p
More than 90% of patients were tolerant to open-label colchicine. Of those who were intolerant, most reported transient gastrointestinal symptoms. In patients randomised into the trial, low-dose colchicine was well tolerated over the longer term: the rate of permanent discontinuation was low (
During a maximum follow-up of five years, low-dose colchicine was not associated with any serious adverse effects. Neutropenia and myotoxicity were rare and no more frequent with the drug than with placebo. No unfavourable effects were found to occur with combined statin therapy even at high doses of statins. The risk of infection leading to hospitalisation or death, or new or fatal cancer, was also no different to placebo.
Dr. Nidorf said: “The trial confirmed that low-dose colchicine was tolerated over the long-term and significantly reduced the risk of the primary endpoint by almost one-third. The benefits were seen soon after initiating therapy, continued to accrue over time, and were observed patients already receiving other effective prevention therapies.”
He noted that the magnitude of colchicine’s effect on cardiovascular outcomes was consistent with that found in the CANTOS and COLCOT trials.4,5 Dr. Nidorf said: “The results of the LoDoCo2 trial establish colchicine as a potential new option for long-term prevention of cardiovascular events in patients with chronic coronary disease. “
Notes to editors
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Funding: National Health Medical Research Council of Australia, Sir Charles Gairdner Research Advisory Committee Grant, Withering Foundation, Netherlands Heart Foundation, Netherlands Organisation for Health Research and Development. The active and placebo tablets were supplied at no cost; Teva, Disphar, and Tiofarma from the Netherlands and Aspen Pharmacare in Australia.
References and notes
1Abstract title: Low-dose colchicine in patients with stable coronary artery disease.
2The LoDoCo2 trial was a collaborative Australian-Dutch investigator-initiated trial conducted by doctors from GenesisCare and the Harry Perkins Institute of Medical Research in Perth Australia, and the Dutch Network for Cardiovascular Research (WCN) in the Netherlands.
3Nidorf SM, Fiolet ATL, Eikelboom JW, et al. The effect of low-dose colchicine in patients with stable coronary artery disease: The LoDoCo2 trial rationale, design, and baseline characteristics. Am Heart J. 2019;218:46-56.
4Ridker PM, Everett BM, Thuren T, et al. Antiinflammatory Therapy with Canakinumab for Atherosclerotic Disease. N Engl J Med. 2017;377:1119-1131.
5Tardif JC, Kouz S, Waters DD, et al. Efficacy and Safety of Low-Dose Colchicine after Myocardial Infarction. N Engl J Med. 2019;381:2497-2505.
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