Low-dose colchicine a boon to chronic coronary disease

Low-dose colchicine reduced the risk of multiple cardiovascular (CV) outcomes in patients with chronic coronary disease, according to the LoDoCo2* trial presented at ESC 2020.

“[C]olchicine [0.5 mg] once daily resulted in a 31 percent lower relative risk of CV death, spontaneous myocardial infarction (MI), ischaemic stroke, or ischaemia-driven coronary revascularization … than placebo,” said Dr Mark Nidorf from GenesisCare, Perth, Australia, and co-authors.

“The benefits were seen soon after initiating therapy, continued to accrue over time, and were observed in patients already receiving other effective prevention therapies,” Nidorf added.

“LoDoCo2 provides strong evidence to support repurposing colchicine for routine secondary prevention in patients with chronic coronary disease,” he said.

Participants in this double-blind trial were 6,528 patients aged 35–82 years from Australia and the Netherlands with clinically stable**, confirmed chronic coronary disease. After a 30-day open-label run-in period where all patients received colchicine (0.5 mg QD), 5,522 clinically stable and adherent patients (mean age 66 years, 15.3 percent female) were randomized 1:1 to continue colchicine or receive placebo. The patients were followed up for a median 28.6 months.

About 84 percent of patients had a history of acute coronary syndrome (ACS) and 18.2 percent had diabetes. Concomitant medications included antiplatelets/anticoagulants (99.7 percent), lipid-lowering agents (96.6 percent), beta blockers (62.1 percent), and renin–angiotensin system inhibitors (71.7 percent).

The risk of the primary composite endpoint of CV death, spontaneous MI, ischaemic stroke, or ischaemia-driven coronary revascularization was significantly reduced with colchicine vs placebo (6.8 percent vs 9.6 percent; hazard ratio [HR], 0.69, 95 percent confidence interval [CI], 0.57–0.83; p<0.001), which translated to 2.5 vs 3.6 events per 100 person-years. [ESC 2020, Hot Line Session; N Engl J Med 2020;doi:10.1056/NEJMoa2021372]

The primary findings favoured colchicine over placebo in multiple subgroups analysed including sex, age, presence of hypertension or diabetes, statin dose, ezetimibe therapy, or prior ACS or coronary revascularization.

Low-dose colchicine also reduced the risk of several secondary endpoints compared with placebo including the key endpoint of a composite of CV death, MI, or ischaemic stroke (4.2 percent vs 5.7 percent; HR, 0.72, 95 percent CI, 0.57–0.92; p=0.007), and the composites of MI or ischaemia-driven coronary revascularization (5.6 percent vs 8.1 percent; HR, 0.67; p<0.001), and CV death or MI (3.6 percent vs 5.0 percent; HR, 0.71; p=0.010).

A reduced risk with colchicine vs placebo was also noted for ischaemia-driven coronary revascularization (4.9 percent vs 6.4 percent; HR, 0.75; p=0.012) and MI (3.0 percent vs 4.2 percent; HR, 0.70; p=0.014), with no significant between-group difference for ischaemic stroke (HR, 0.66; p=0.198) or any-cause death (HR, 1.21).

Non-CV-related death occurred in more colchicine than placebo recipients (0.7 vs 0.5 per 100 person-years; HR, 1.51). New cancer diagnosis (4.3 percent vs 4.4 percent) and hospitalization rates for infection (5.0 percent vs 5.2 percent), pneumonia (1.7 percent vs 2.0 percent), or gastrointestinal (GI) events (1.9 percent vs 1.8 percent) were similar between colchicine and placebo recipients. Incidents of neutropenia and myotoxicity were rare. Gout occurred in fewer colchicine than placebo recipients (1.4 percent vs 3.4 percent), while myalgia*** occurred in more colchicine than placebo recipients (21.2 percent vs 18.5 percent). Permanent premature treatment discontinuation occurred in 10.5 percent of each group.

Old drug, new tricks?

“These results are quite impressive. This suggests that colchicine could be considered an efficacious and safe treatment to be added on top of standard medical therapy for coronary syndrome,” said discussant Professor Massimo Imazio from the University of Turin, Italy. [https://www.youtube.com/watch?v=nHOsZXbwMNg, accessed 18 September 2020]

“[Evidence from the] LoDoCo2 and COLCOT^# [trials suggest] that this drug is also efficacious and safe in patients with ACS so two spectrums of coronary syndrome could be treated with colchicine added on top of standard anti-inflammatory therapy,” he added.

He highlighted the importance of using a low dose of colchicine, noting the 10 percent premature discontinuation rate due to GI events, which could be amplified with a loading dose. He also pointed out potential drug–drug interactions in patients with coronary syndrome, advocating for monitoring blood count and transaminase levels.

The results suggest a paradigm change in the treatment of coronary disease where an old, cheap drug has new CV indications, he concluded.