Abstract Body: Background
The trial of colchicine in high risk patients with acute minor-to-moderate ischaemic stroke or transient ischaemic attack (CHANCE-3) evaluated the efficacy and safety of low dose colchicine on reducing subsequent stroke within three month. The study did not provide any evidence showing that colchicine could reduce the risk of any stroke within three months after onset, possibly due to heterogeneity of treatment effect (HTE) across patients. Better assessing HTE could identify some subpopulations with derived benefit.
Objective
In the post-hoc analysis, we aimed to assess HTE through different approaches and explore the subgroup of patients who may benefit from colchicine.
Method
Exploratory analysis of a multicentre, double blind, randomised, controlled trial of low dose colchicine versus placebo in patients with a minor-to-moderate ischaemic stroke or transient ischaemic attack and a high sensitivity C-reactive protein ≥2 mg/L. The primary outcome was any new stroke within three month after onset. Heterogeneity of treatment effect was assessed two ways: using a multivariable outcome prediction model, and a causal forest model. Cox proportional hazards models were used to evaluate the effect of colchicine in subgroup patients with specific characteristics.
Results
The trial enrolled and assigned 8,343 patients to colchicine or placebo group and baseline characteristics were balanced between two groups (mean age, 65.6 years; 62.4% male). In the overall population, colchicine was not associated with an decreasing risk of stroke (HR: 0.98, 95%CI: 0.83-1.16, p =0.79). Based on causal forest models, mean corpusular volume, triglyceride, BMI, and the neutrophil count distinguished patients who differentially benefited from colchicine (interaction p =0.02). Cox proportional hazards models revealed a number needed to treat of 29.4 to prevent one stroke among participants with mean corpusular volume higher than 86.2 g/L, triglyceride higher than 1.39 mmol/L, BMI higher than 23.39 Kg/m², and the neutrophil count higher than 4.35×10⁹/L (HR: 0.65, 95%CI: 0.44-0.94, p =0.02).
Conclusion
Among patients with acute minor-to-moderate ischaemic stroke or transient ischaemic attack, the effect of colchicine on stroke within three months was heterogeneous. Approaches to assessing HTE could identify individuals who might have derived benefit, which shed light on the design and analysis of further trials.