Effects of colchicine use on ischemic and hemorrhagic stroke risk in diabetic patients with and without gout

Abstract

This study aimed to determine the effect of colchicine use on the risk of stroke among patients with diabetes mellitus (DM). We retrospectively enrolled patients with DM between 2000 and 2013 from the Longitudinal Health Insurance Database and divided them into a colchicine cohort (n = 8761) and noncolchicine cohort (n = 8761) by using propensity score matching (PSM). The event of interest was a stroke, including ischemic stroke and hemorrhagic stroke. The incidence of stroke was analyzed using multivariate Cox proportional hazards models between the colchicine cohort and the comparison cohort after adjustment for several confounding factors. The subdistribution hazard model was also performed for examination of the competing risk. The colchicine cohort had a significantly lower incidence of stroke [adjusted hazard ratios (aHR), 95% confidence intervals (95%CI)] (aHR = 0.61, 95%CI = 0.55–0.67), ischemic stroke (aHR = 0.59, 95%CI = 0.53–0.66), and hemorrhagic stroke (aHR = 0.66, 95%CI = 0.53–0.82) compared with the noncolchicine cohort. Drug analysis indicated that patients in the colchicine cohort who received colchicine of cumulative daily defined dose (cDDD) > 14 and duration > 28 days had a lower risk of stroke and ischemic stroke compared with nonusers. The colchicine cohort (cDDD > 150, duration > 360 days) also had a lower risk of stroke, ischemic stroke, and hemorrhagic stroke. The cumulative incidence of stroke, ischemic stroke, and hemorrhagic stroke in the colchicine cohort was significantly lower than that in the noncolchicine cohort (log-rank P < 0.001). However, the subdistribution hazard model reveal the colchicine was not associated with the hemorrhagic stroke in DM patients without gout (aHR = 0.69, 95%CI = 0.47–1.00). Colchicine use with cDDD > 14 and duration > 28 days was associated with lower risk of stroke and ischemic stroke, and colchicine use with cDDD > 150 and duration > 360 days played an auxiliary role in the prevention of stroke, ischemic stroke, and hemorrhagic stroke in patients with DM. The colchicine for the hemorrhagic stroke in DM patients without gout seem to be null effect.

Perspective: Collagen induced platelet activation via the GPVI receptor as a primary target of colchicine in cardiovascular disease

“…Recent clinical trials targeting GPVI either directly with ACT017, Voors-Pette et al ( 10 ) or indirectly with Revacept, Uphaus et al ( 9 ) have shown great promise in reducing collagen-mediated platelet activation and improved stroke outcome without leading to bleeding complications ( 64 ). Colchicine reduces the risk of hemorrhagic and ischemic stroke ( 65 – 67 ), which is consistent with the reduction observed for Revacept both in a mouse stroke model ( 36 ) and a human carotid stenosis clinical trial ( 9 ), however colchicine has additional anti-inflammatory affects. Like ACT017 and Revacept, colchicine treatment has not been linked to bleeding complications.…”

A systematic review on the use of Colchicine in Hemorrhagic Stroke

“…The included study by Jun-Jun Yeh et al 9 is a retrospective cohort study that aimed to investigate the effect of colchicine use on the risk of stroke among patients with diabetes mellitus. The study was conducted between 2000 and 2013 and enrolled a total of 17,522 patients with diabetes mellitus from the Longitudinal Health Insurance Database.…”

“…However, the study found that colchicine was not associated with hemorrhagic stroke in DM patients without gout. 9 …”