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Colchicine is a widely available, inexpensive drug with a range of anti-inflammatory properties, but can it address an unmet need and reduce cardiovascular (CV) events in patients with coronary artery disease (CAD)? Today, Doctor Mark Nidorf (GenesisCare, Australia) revealed the answer as he presented results from the LoDoCo2 trial as a Hot Line at ESC Congress 2020.
LoDoCo2 was an investigator-initiated, international trial in which 5,522 patients with stable CAD tolerant to colchicine during a 30-day run-in phase were randomised to colchicine 0.5 mg daily or placebo on a background of optimal lipid lowering and antithrombotic therapy.
During a median follow-up of almost 30 months, a significant reduction in CV events was observed with low-dose colchicine vs. placebo. The primary endpoint (CV death, myocardial infarction [MI], ischaemic stroke or ischaemia-driven coronary revascularisation) 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 MI 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 the randomisation phase, the rate of permanent discontinuation was low (<10%) in the colchicine group and similar to that in the placebo group. During a maximum follow-up of 5 years, colchicine was not associated with any serious adverse effects. Neutropenia and myotoxicity were rare and no more frequent with colchicine than with placebo. No unfavourable effects were reported with combined statin therapy even at high statin doses. The risk of infection leading to hospitalisation or death, or new or fatal cancer, was also no different to placebo.
Dr. Nidorf explained, “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 in patients already receiving other effective prevention therapies.” He noted that the magnitude of colchicine’s effect on CV outcomes was similar to that observed in the CANTOS trial with canakinumab and in the COLCOT trial with low-dose colchicine after MI.1,2
“The results of the LoDoCo2 trial establish colchicine as a potential new option for long-term prevention of CV events in patients with chronic coronary disease,” concluded Dr. Nidorf.
Watch the presentation
1. Ridker PM, et al. N Engl J Med 2017;377:1119–1131.
2. Tardif JC, et al. N Engl J Med 2019;381:2497–2505.
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