Colchicine therapy in patients with coronary artery disease: a systematic review and meta-analysis of randomized controlled trials

Abstract

Introduction Inflammation is a substantial mediator of atherosclerosis. Colchicine has anti-inflammatory effects and has been investigated in many randomized controlled trials (RCTs) in patients with coronary artery disease (CAD). Methods We searched PubMed/MEDLINE, Cochrane library, and Embase databases (inception through 28 February 2020) for RCTs evaluating colchicine in CAD patients. The outcomes of interest were major adverse cardiovascular events (MACE), myocardial infarction (MI), all-cause mortality, cardiovascular mortality, and stroke. Estimates were pooled using inverse-variance random-effects model. We reported effect sizes as risk difference (RD) with 95% confidence interval (CI). Results A total of six RCTs with 6154 patients were included. The mean age ± SD for the patients in the colchicine group was 61.6 ± 10.8 and control group was 61.5 ± 10.7 years. At the median follow-up of 3.5 months, use of colchicine in patients with CAD was not associated with statistically significant reduction of MACE (RD −0.032; 95% CI −0.083 to 0.018; P = 0.15; I2 = 75%; low level of evidence), MI (RD −0.011; 95% CI −0.030 to 0.007; P = 0.16; I2 = 11.3%; low level of evidence), all-cause mortality (RD −0.001; 95% CI −0.009 to 0.006; P = 0.65; I2 = 0%; low level of evidence), cardiovascular mortality (RD −0.003; 95% CI −0.010 to 0.004; P = 0.34; I2 = 0%; low level of evidence), and stroke (RD −0.001, 95% CI −0.005 to 0.004; P = 0.69; I2 = 0%; very low level of evidence). Conclusion This meta-analysis suggests that colchicine was not associated with a significant decrease in cardiovascular endpoints and mortality in patients with CAD.

Long-term cardiovascular safety of febuxostat compared with allopurinol in patients with gout (FAST): a multicentre, prospective, randomised, open-label, non-inferiority trial

“…Although some recent trials have demonstrated that treatment with colchicine improved outcomes in patients with recent myocardial infarction, and chronic coronary disease, published evidence that treatment with colchicine may be associated with improvements in cardiovascular outcomes has been inconsistent. [20][21][22][23] In FAST, while prophylaxis against flares of gout was offered to all patients, only some accepted it, those who took it mainly did so at the very beginning of the trial, and it is likely that some patients chose to take it for less than the six months provided. It is unlikely that the relatively short-term administration of low dose colchicine or NSAIDs as prophylaxis, or any differences in concomitant use of colchicine or NSAIDs, even with the imbalances between treatment groups, had any major effect on the long-term outcomes of FAST.…”

Efficacy and Safety of Colchicine in Post–acute Myocardial Infarction Patients: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

“…One review included patients with ACS; however, only a narrative synthesis was conducted (8). Moreover, six reviews (5)(6)(7)(9)(10)(11) pooled data from patients with chronic coronary syndrome and ACS, despite the fact that these populations are clinically different. In contrast to our findings, four previous reviews (7)(8)(9)11) reported that colchicine was associated with an increased risk of gastrointestinal adverse events.…”

“…In contrast to our findings, four previous reviews (7)(8)(9)11) reported that colchicine was associated with an increased risk of gastrointestinal adverse events. Only one review used the Hartung-Knapp adjustment for CIs (5). Besides, quality of evidence per outcome using GRADE methodology was evaluated in only one review (5).…”

“…High levels of hs-CRP following an acute coronary event have been associated with increased short- and long-term risk of recurrent cardiovascular events and mortality ( 39 , 40 ). There are conflicting data on whether colchicine can reduce hs-CRP levels in patients with CAD ( 5 , 8 ). Our study found no significant difference on pooled hs-CRP levels during follow-up between patients treated with colchicine or placebo.…”

“…Colchicine is a low-cost drug with wider anti-inflammatory properties that has been used for more than 200 years for the treatment of gout attacks and currently in other inflammatory diseases such as acute pericarditis and familial Mediterranean fever. Few systematic reviews have examined the effect of colchicine in patients with CAD (5)(6)(7)(8)(9)(10)(11), but none focused on post-acute MI patients. The analysis of its effect specifically on MI patients is important because of the intense inflammatory response associated with acute MI and the high risk for poor outcomes in these patients in whom the anti-inflammatory effect of colchicine may be more relevant.…”