Colchicine for Secondary Prevention After Stroke According to the Presence of Atherosclerosis

BACKGROUND: Anti-inflammatory therapies reduce the risk of major adverse cardiovascular events (MACEs) in coronary disease, but efficacy has not been shown after stroke. It is uncertain if patients with atherosclerosis are more likely to benefit from anti-inflammatory prevention. METHODS: We performed a post hoc analysis of the CONVINCE trial (randomized, open-label, blinded-end point assessed; Colchicine for Prevention of Vascular Inflammation in Non-Cardioembolic Stroke), comparing colchicine 0.5 mg plus usual care versus usual care. We performed a subgroup analysis in patients stratified according to the presence/absence of atherosclerosis (defined as cervico-cranial/aortic artery plaque, coronary disease, peripheral arterial disease, and carotid revascularization). The primary outcome was MACE. Analyses were adjusted for age, qualifying event, time from event to randomization, and coronary disease. RESULTS: Three thousand one hundred forty-four participants were included. There were 338 MACE events during follow-up (median, 33.6 months). On intention-to-treat analysis, there were numerically fewer MACE events in the atherosclerosis group assigned to colchicine (105 [11.1%], 3.88 [95% CI, 3.21–4.70] per 100 person-years) versus usual care (132 [14.2%], 4.83 [4.07–5.73] per 100 person-years), which was not statistically significant (hazard ratio [HR], 0.83 [95% CI, 0.64–1.07]). There was no difference in the rate of the primary outcome according to treatment allocation in the nonatherosclerosis subgroup (HR, 0.94 [95% CI, 0.64–1.39]; P interaction =0.60). There was a nonsignificant reduced risk of recurrent ischemic stroke in the colchicine arm (HR, 0.76 [95% CI, 0.56–1.05]) in the atherosclerosis group, but no difference in events was observed in the nonatherosclerotic group (HR, 0.92 [95% CI, 0.60–1.42]; P interaction =0.48). In the prespecified on-treatment analysis, colchicine reduced the risk of MACE in patients with atherosclerosis (HR, 0.76 [95% CI, 0.58–0.99]) but not without (HR, 0.95 [95% CI, 0.63–1.42]; P interaction =0.37). CONCLUSIONS: There were no significant between-group interactions for colchicine and atherosclerosis for MACE in intention-to-treat or on-treatment populations. However, outcome events were numerically fewer in patients with atherosclerosis assigned to colchicine, and significant benefit was observed in the on-treatment analysis in this group. Data suggest that the presence of atherosclerosis should be an inclusion criterion in future anti-inflammatory therapy trials. REGISTRATION: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT02898610.