Anti-inflammatory drug reduces CV death and ischemic events in chronic coronary disease
LoDoCo2 Low-Dose Colchicine in Coronary Disease
Presented at the ESC congress 2020 by: Mark Nidorf, MD (Perth, Australia)
Introduction and methods
Colchicine inhibits several inflammatory pathways in atherosclerosis and is used in the treatment of gout. The LoDoCo (Low Dose Colchicine) pilot trial previously suggested that colchicine 0.5mg was safe and effective for preventing CV events in patients with coronary artery disease.
The current LoDoCo2 trial was an investigator-initiated, double-blind, placebo-controlled, event-driven trial that aimed to determine whether colchicine 0.5mg once daily prevents CV events in patients with chronic coronary disease.
A total of 6528 patients (aged 35-82 years) with proven coronary disease enrolled in the 30-day open label run-in of colchicine 0.5 mg daily. Patients were clinically stable for ≥6 months, and no advanced renal disease, heart failure or severe heart disease. 91.3% of patients tolerated the open label therapy. A total of 5522 patients who were tolerant, clinically stable and willing to proceed were randomized to receive colchicine 0.5 mg once daily (n=2762, mean age was 65.8 years, 83.5% were male) or placebo (n=2760, mean age was 65.9 years, 85.9% were male) on a background of lipid lowering and antithrombotic therapy. Median follow-up was 29 months (12-64 months).
A total of 5522 patients (aged 35-82 years) with proven coronary disease were randomized to receive colchicine 0.5 mg once daily (n=2762, mean age was 65.8 years, 83.5% were male) or placebo (n=2760, mean age was 65.9 years, 85.9% were male) on a background of lipid lowering and antithrombotic therapy. Patients were clinically stable for ≥6 months, had no advanced renal disease, heart failure or severe heart disease, and were tolerant to colchicine during a 30-day open label run-in phase. Median follow-up was 29 months (12-64 months).
The primary endpoint was a composite of CV death, myocardial infarction (MI), ischemic stroke, or ischemia-driven coronary revascularization.
- Colchicine reduced the risk for the primary composite endpoint by 31%, compared to placebo (HR 0.69, 95%CI 0.57-0.83, P<0.001). The effects of colchicine were seen to occur early and continued to accrue over time.
- The effect of colchicine extended to the first 5 of 8 ranked secondary endpoints including 1) the composite of CV death, MI or ischemic stroke (HR 0.72, 95%CI 0.57-0.92, P=0.007), 2) the composite of MI or ischemia-driven coronary revascularization (HR 0.67, 95%CI 0.55-0.83, P<0.001), 3) CV death or MI (HR 0.71, 95%CI 0.55-0.92, P=0.010), 4) ischemia-driven coronary revascularization (HR 0.75, 95%CI 0.60-0.94, P=0.012), and 5) MI (HR 0.70, 95%CI 0.53-0.93, P=0.014). No significant effects with colchicine, compared to placebo, were found for the following individual secondary end points: ischemic stroke, all-cause mortality and CV death.
- The effect of colchicine was also consistent across a number of prespecified sub-groups, including men and women, those who were older and younger than 65 years, and those with and without a history of hypertension.
- There were no statistically significant differences in serious adverse events between the two treatment groups.
Low-dose colchicine (0.5 mg once daily) reduced the risk of the primary composite endpoint (CV death, MI, ischemic stroke, or ischemia-driven coronary revascularization) and key secondary endpoints in patients with chronic coronary disease. Colchicine appeared safe with no statistically significant differences in serious adverse events compared to placebo.
The discussant Massimo Imazio, MD (Turin, Italy) congratulates the investigators for a well-designed RCT that in his opinion provides convincing evidence that colchicine is effective and safe for secondary prevention in chronic coronary syndromes (if tolerated). Imazio notes that it is important to use low doses (0.5 mg/day) of colchicine without a loading dose and that it can be expected that up to 10% of patients will not tolerate and benefit from the drug, mainly because of gastrointestinal side effects. Furthermore, it remains important to be aware of potential side effects and interactions and appropriate blood tests (such as blood cell count, transaminases and CK) are indicated. Imazio concludes that the LoDoCo2 trial and COLCOT trial have contributed to the growing evidence that colchicine on top of standard medical therapy can reduce CV events in patients with chronic (LoDoCo2) and acute coronary syndromes (COLCOT).
-Our reporting is based on the information provided at the ESC congress -