Gout drug repurposed to fight heart disease
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.
"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 randomized 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. 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<0.001). When the components of the primary endpoint were analysed separately, a consistent trend was seen with all endpoints and myocardial infarction and ischaemia-driven coronary revascularisation were both significantly less frequent in the colchicine group.
More than 90% of patients were tolerant to open-label colchicine. Of those who were intolerant, most reported transient gastrointestinal symptoms. In patients randomized into the trial, low-dose colchicine was well tolerated over the longer term: the rate of permanent discontinuation was low (<10%) and similar to those taking placebo.
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 unfavorable effects were found to occur with combined statin therapy even at high doses of statins. The risk of infection leading to hospitalization 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. 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."
Stefan M. Nidorf et al, Colchicine in Patients with Chronic Coronary Disease, New England Journal of Medicine (2020). DOI: 10.1056/NEJMoa2021372