AIMS: The key role of inflammation in the pathogenesis of coronary artery disease (CAD) is an urgent call for innovative treatments. Several trials have proposed colchicine as a therapeutic option for secondary prevention in CAD patients but its utilization is hampered by fears about drug-related adverse events (DAEs) and conflicting evidences. The aim of this meta-analysis was to consolidate evidence on the efficacy and safety of colchicine for secondary prevention in patients with CAD.METHODS AND RESULTS: A systematic search in electronic bibliographic databases of Medline, Scopus, Embase, and the Cochrane Library was performed to identify randomized controlled trials (RCTs) assessing the cardiovascular effects of colchicine in CAD patients, compared with placebo. Outcomes of interest were the occurrence of major adverse cardiovascular and cerebrovascular events (MACCE) and DAEs. Estimates were pooled using inverse-variance random-effects model. A total of 11 RCTs, including 12869 patients, were identified as eligible. A total of 6501 patients received colchicine, while 6368 received placebo. After a median follow-up of 6months (interquartile range, 1-16), patients receiving colchicine had a lower risk of MACCE [6% vs. 8.8%, relative risk (RR) = 0.67, 95% confidence interval (CI) 0.56-0.80, I2=19%], myocardial infarction (3.3% vs. 4.3%, RR=0.76, 95% CI 0.61-0.96, I2=17%), coronary revascularization (2.9% vs. 4.2%, RR=0.61, 95% CI 0.42-0.89, I2=40%), stroke (0.4% vs. 0.9%, RR=0.48, 95% CI 0.30-0.77, I2=0%), hospitalization for cardiovascular cause (0.9% vs. 2.9%, RR=0.32, 95% CI 0.12-0.87, I2=0%). Colchicine was associated with an increased risk of gastrointestinal DAEs (11% vs. 9.2%, RR=1.67, 95% CI 1.20-2.34, I2=76%), myalgia (18% vs. 16%, RR = 1.16, 95% CI 1.02-1.32, I2=0%) and DAEs-related discontinuation (4.1% vs. 3%, RR = 1.54, 95% CI 1.02-2.32, I2=65%). However, gastrointestinal DAEs and discontinuation may be prevented with a lower daily dose. Colchicine did not increase the risk of cardiovascular death (0.7% vs. 1%, RR=0.73, 95% CI 0.45-1.21, I2=14%), all-cause death (2% vs. 1.9%, RR=1.01, 95% CI 0.71-1.43, I2=16%), or other DAEs.CONCLUSIONS: The use of colchicine in patients with CAD is safe and efficacious for MACCE prevention.
Efficacy and safety of colchicine for the prevention of major cardiovascular and cerebrovascular events in patients with coronary artery disease: a systematic review and meta-analysis on 12 869 patients
Andreis, AlessandroFirst
;Piroli, Francesco;Avondo, Stefano;Casula, Matteo;Paneva, Elena;De Ferrari, Gaetano MariaLast
2021-01-01
Abstract
AIMS: The key role of inflammation in the pathogenesis of coronary artery disease (CAD) is an urgent call for innovative treatments. Several trials have proposed colchicine as a therapeutic option for secondary prevention in CAD patients but its utilization is hampered by fears about drug-related adverse events (DAEs) and conflicting evidences. The aim of this meta-analysis was to consolidate evidence on the efficacy and safety of colchicine for secondary prevention in patients with CAD.METHODS AND RESULTS: A systematic search in electronic bibliographic databases of Medline, Scopus, Embase, and the Cochrane Library was performed to identify randomized controlled trials (RCTs) assessing the cardiovascular effects of colchicine in CAD patients, compared with placebo. Outcomes of interest were the occurrence of major adverse cardiovascular and cerebrovascular events (MACCE) and DAEs. Estimates were pooled using inverse-variance random-effects model. A total of 11 RCTs, including 12869 patients, were identified as eligible. A total of 6501 patients received colchicine, while 6368 received placebo. After a median follow-up of 6months (interquartile range, 1-16), patients receiving colchicine had a lower risk of MACCE [6% vs. 8.8%, relative risk (RR) = 0.67, 95% confidence interval (CI) 0.56-0.80, I2=19%], myocardial infarction (3.3% vs. 4.3%, RR=0.76, 95% CI 0.61-0.96, I2=17%), coronary revascularization (2.9% vs. 4.2%, RR=0.61, 95% CI 0.42-0.89, I2=40%), stroke (0.4% vs. 0.9%, RR=0.48, 95% CI 0.30-0.77, I2=0%), hospitalization for cardiovascular cause (0.9% vs. 2.9%, RR=0.32, 95% CI 0.12-0.87, I2=0%). Colchicine was associated with an increased risk of gastrointestinal DAEs (11% vs. 9.2%, RR=1.67, 95% CI 1.20-2.34, I2=76%), myalgia (18% vs. 16%, RR = 1.16, 95% CI 1.02-1.32, I2=0%) and DAEs-related discontinuation (4.1% vs. 3%, RR = 1.54, 95% CI 1.02-2.32, I2=65%). However, gastrointestinal DAEs and discontinuation may be prevented with a lower daily dose. Colchicine did not increase the risk of cardiovascular death (0.7% vs. 1%, RR=0.73, 95% CI 0.45-1.21, I2=14%), all-cause death (2% vs. 1.9%, RR=1.01, 95% CI 0.71-1.43, I2=16%), or other DAEs.CONCLUSIONS: The use of colchicine in patients with CAD is safe and efficacious for MACCE prevention.
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