Abstract Background Colchicine is the most widely studied anti-inflammatory drug for patients with coronary artery disease (CAD), and has recently received a class IIa indication for administration in these patients by international guidelines. However, the recent CLEAR trial, the largest trial of colchicine in patients with acute coronary syndrome (ACS) to date, significantly challenged this recommendation. Among potential factors influencing the efficacy of colchicine, lower efficacy in ACS rather than chronic coronary syndrome (CCS), timing of administration and contemporary administration of other therapies have been claimed. Purpose To evaluate the benefits of colchicine in patients with CAD and the specific subgroups od CCS and ACS. Methods Randomized trials of colchicine in patients with CAD undergoing PCI were identified. Trial-defined major adverse cardiovascular events (MACE), a composite of cardiovascular death, myocardial infarction and stroke, and serious adverse events (SAE) were the primary efficacy and safety outcomes, respectively. Secondary outcomes included all-cause death and single components of the primary endpoints. Pairwise meta-analyses with interaction for the clinical presentation (i.e., ACS or CCS) and dosage (high- or low-dose) were conducted. Results A total of 19 studies including 21,425 patients were included. Of these, 7,435 (34.7%) were CCS patients. Compared with control, colchicine was associated with a significant reduction in MACE (IRR 0.71; 95% CI 0.58-0.88; Figure 1) without significant increase in SAE (IRR 0.95; 95% CI: 0.86-1.05). Colchicine also reduced rates of myocardial infarction (IRR 0.82; 95% CI 0.71-0.96) and any revascularization (IRR 0.74; 95% CI 0.55-0.99). Among other safety measures, colchicine administration was associated with significantly higher rates of gastrointestinal adverse events (IRR 1.68; 95% CI 1.23-2.28). No significant interaction between efficacy and clinical presentation was found (Figure 2), but a significant interaction for gastrointestinal adverse events and colchicine dose was detected (P=0.014), as the effects were primarily driven by high-dose colchicine (IRR 2.33; 95% CI 1.43-3.79). Conclusions In patients with CAD, colchicine administration reduces MACE, myocardial infarction and any revascularization independently of the clinical presentation. Colchicine was associated with a significant increase in non-serious gastrointestinal adverse events, which was more apparent in patients receiving higher dosages. In aggregate, these data suggest that low-dose colchicine may allow better net benefit profile across the whole spectrum of coronary artery disease.Figure 2.Interaction for presentation
Laudani et al. (Sat,) studied this question.