Colchicine offers cardioprotection in coronary artery disease following PCI

Treatment with colchicine appears to produce a significant reduction in the risk of major adverse cardiovascular events (MACE) in coronary artery disease (CAD) patients who underwent percutaneous coronary intervention (PCI), according to the results of a systematic review and meta-analysis.

Pooled data from seven randomized controlled trials showed a 27-percent decrease in the odds of having MACE following PCI with the use of colchicine (risk ratio, 0.73, 95 percent confidence interval, 0.61–0.87; p=0.0003), with minimal heterogeneity across the analysis (I², 6 percent; p=0.38). [Open Heart 2022;9:e001887]

The lower risk of MACE was driven mainly by the reduction in repeat vessel revascularization, stroke, and stent thrombosis. The number needed to treat to prevent one occurrence of MACE with colchicine was 41.

Colchicine is a cheap and relatively low risk medication, the investigators noted, adding that its beneficial effect is likely attributable to its wide-ranging effects on the inflammatory process.

“[The drug] concentrates in leukocytes and has a primary antimitotic effect against microtubule and spindle formation. It also induces downregulation of various inflammatory pathways further impacting neutrophil activation and recruitment, platelet aggregation, and the expression of various cytokines and interleukins,” they explained. [Eur Heart J Cardiovasc Pharmacother 2021;7:e18-19]

Indeed, several studies have demonstrated that an acute colchicine administration leads to a pronounced reduction in the transcoronary production of the inflammasome-specific cytokines IL-1β, IL-18, and downstream IL-6, all of which are elevated in patients presenting with acute coronary syndrome (ACS). [Int J Cardiol 2017;236:95-99; J Am Heart Assoc 2015;4:e002128; Clin Sci 2016;130:1237-1246]

The current meta-analysis included a total of 6,660 CAD patients (mean age 60.9 years) who underwent PCI, of which 3,347 were in the colchicine group and 3,313 were in the control group. Six studies included participants who had a ≤13.5-day history of ACS, whereas one study involved patients with both ACS and chronic coronary syndrome.

Colchicine was administered after PCI in five studies, before PCI in one study, and either before or after balloon angioplasty in one study. The follow-up of studies ranged from 3 days to 22.6 months. MACE occurred in 237 patients the colchicine group and in 303 patients in the control group (7.08 percent vs 9.15 percent).

“Our study is novel in two ways: we study the effects of colchicine only in patients who underwent both PCI and medical therapy, and we provide an updated systematic review and meta-analysis including a recently published major trial—the Colchicine in Patients with Acute Coronary Syndrome (COPS) trial,” according to the investigators.

Despite the encouraging results, the investigators acknowledged that before colchicine can be used in routine clinical practice, additional studies are required to fully assess the drug’s role in the treatment of ischaemic heart disease.

“There is promising potential in its use in a PCI setting, but further evaluation particularly in distinguishing between different stents (bare-metal vs drug-eluting), categorizing patients based on myocardial infarction (MI) type (ST elevation MI [STEMI] vs non-STEMI), as well as personalizing colchicine use in terms of duration of treatment and dose would be needed,” they said.

“[Ongoing] trials such as the CLEAR SINERGY neutrophil substudy which examines clinical and genetic factors that determine heterogeneity in response to colchicine treatment may be a step in the right direction, suggesting that perhaps colchicine will be used in a selected population in the appropriate clinical setting,” according to the investigators.