Abstract Background Chronic inflammation is implicated in the pathogenesis of cardiovascular disease (CVD). The use of colchicine, a common anti-inflammatory drug, has been incorporated into major clinical guidelines for secondary CVD prevention. However, recent randomized trials presented contravening results. Study dosage and duration varied. Purpose To synthesise the current randomized trial evidence of colchicine in the secondary protection against CVD, using a cumulative dose approach. Methods A meta-analysis incorporating all randomized controlled trials (RCT) globally was performed. Comprehensive search was conducted in PubMed, EMBASE, and Cochrane Library, following PRISM and Cochrane risk-of-bias assessment (RoB2). RCTs directly comparing colchicine versus placebo/ standard care for the secondary prevention in acute atherothrombotic (cerebrovascular or coronary), or all CVD were included. Cumulative colchicine exposure was defined as dose-time composite of colchicine exposure (measure unit: mg-days). Odds ratios (OR) were derived (random-effects, Mantel-Haenszel and DerSimonian-Laird) for the primary outcome, defined as prospective occurrence of Major Adverse Cardiovascular Events (MACE). Secondary outcomes included mortality, individual components of MACE, C-reactive protein (CRP), and adverse effects. Results Thirteen RCTs including 31,397 participants were included for final analyses. Colchicine significantly reduced MACE (OR=0.75, 95% CI: 0.62 - 0.90) in both acute atherothrombotic CVD and all CVD (0.70, 95% CI: 0.58 - 0.84) (Figure A), and resulted in significant prospective reductions in CRP (-0.27mg/L, 95%CI -0.53 to -0.02) (Figure B). Threshold effect was apparent with a protective benefit of colchicine against MACE at higher cumulative exposure ≥90mg-days (≥90mg-days: OR=0.66, 95%CI 0.52-0.84, 90mg-days: OR=0.93, 95%CI 0.79-1.09, P for between-groups difference=0.02). Colchicine resulted in no differences in cardiovascular or non-cardiovascular mortality. Gastrointestinal upset was more frequent in the colchicine group (OR=1.95, 95%CI 1.29-2.94), mainly non-serious and was associated with open-label design of RCTs (P=0.03). Conclusions Colchicine significantly reduces MACE in both acute atherothrombotic and all CVD across multiple ethnicities, with a threshold protective effect that clinically corresponds to treatment of 0.5mg daily for at least 6 months. Importantly, there was no signal of an increased all-cause mortality.
Chan et al. (Sat,) studied this question.