Colchicine substantially reduces major adverse cardiovascular events (MACE) including cardiovascular death, myocardial infarction (MI) and ischemic stroke compared with placebo in patients with vascular disease, according to two meta-analyses of randomized controlled trials (RCTs) published May 2 in the European Heart Journal.

In one study, Michelle Samuel, MPH, PhD, et al., conducted an updated systematic review and meta-analysis of six RCTs (including two recently published studies) with long-term follow-up (12-34 months) in 21,800 patients with vascular disease (post MI, stroke and stable coronary artery disease [CAD]) taking a daily low dose (0.5 mg/day) of colchicine plus guideline-directed therapy (10,871 taking colchicine vs. 10,929 taking placebo).

Results showed that colchicine vs. placebo substantially reduced the primary efficacy endpoint of MACE (a composite of cardiovascular death, MI, ischemic stroke and urgent coronary revascularization) by 25%. For the individual endpoints, colchicine reduced MI by 29%, ischemic stroke by 37% and urgent coronary revascularization by 33% (p<0.05 for all). No differences were observed for all-cause (relative risk [RR], 1.01) or noncardiovascular mortality (RR, 1.08) or hospitalizations for gastrointestinal (GI) events (RR, 1.17) between the two groups.

The authors write that "the results support the use of colchicine to reduce recurrent cardiovascular events" because of its safety and protection against MACE in patients with vascular disease.

In a second, study-level, meta-analysis, Marc-André d'Entremont, MD, et al., systematically reviewed nine RCTs including 30,659 patients with CAD or stroke, comparing colchicine (n=15,255) vs. no colchicine (n=15,404) for the secondary prevention atherosclerotic cardiovascular disease (ASCVD).

Results showed that patients randomized to colchicine, compared with none, had a 12% relative risk reduction (0.88% absolute risk reduction) in the primary composite outcome of cardiovascular death, MI or stroke. For the individual endpoints, the reduction in the relative risk was 6% for cardiovascular death, 16% for MI and 10% for stroke.

Looking at safety endpoints, there was a 35% increase in the relative risk for hospitalization for gastrointestinal (GI) events, but no increase for pneumonia hospitalizations or noncardiovascular mortality with colchicine compared with no colchicine.

Considering the potential increase in GI events, the authors write that "shared decision-making between clinicians and patients is essential in balancing the benefits and harms when prescribing colchicine in secondary ASCVD prevention."

In an accompanying editorial comment, Stuart J. Pocock, PhD, and Guiomar Mendieta, MD, acknowledge the "positive conclusions" for MACE outcomes in both meta-analyses and "modest benefits" of colchicine in patients with CAD. When analyzing the totality of evidence regarding colchicine, however, they write that "diversity of trial designs means no generalizable overall conclusion is possible." They also express the need for more effective individualized anti-inflammatory treatments besides colchicine in the current era of personalized medicine.