Aernoud Fiolet

78 Chapter 3 PROSPECTIVE STUDIES ON COLCHICINE IN PATIENTS WITH STABLE CORONARY ARTERY DISEASE A number of trials have shown that low-dose colchicine can reliably reduce levels of inflammatory markers, including high-sensitivity C-reactive protein (hs-CRP) and interleukin-6, in patients with heart failure and in patients undergoing ablation for atrial fibrillation; however, only one randomized trial has examined the biochemical effect in patients with stable coronary disease. 32,33,34 Among 64 patients with stable coronary disease who had elevated hs-CRP levels despite high- dose statin therapy, colchicine 0.5 mg BID reliably and rapidly lowered hs-CRP levels over a 4-week period. This observation provided hope that colchicine may have anti-inflammatory effects over and above statin and antiplatelet therapy. It also led to the first LoDoCo (Low-Dose Colchicine) trial, which examined the effect of colchicine in patients with stable coronary disease who were on optimal medical therapy and recruited without reference to baseline levels of hs-CRP. 35 LoDoCo used a prospective, randomized, observed-blinded end point design in which patients were randomized to receive either colchicine 0.5 mg once daily or regular clinical follow-up. 35 After a median follow-up of 3 years, a significant difference in favor of colchicine treatment was observed in the occurrence of the primary outcome (HR, 0.33; 95% CI, 0.18–0.59). The primary outcome in the trial consisted of cardiovascular death, non-cardioembolic stroke, acute coronary syndrome, and out-of-hospital cardiac arrest. It was mainly driven by a reduction in acute coronary syndromes (72%), of which more than one half were episodes of unstable angina irrespective of revascularization. The risk for observer bias ought to be minimalized with the blinded end point assessment, although residual information bias still might play a role in treatment decisions. However, this very pragmatic trial provided the first clinical data on the efficacy of colchicine as a strategy of secondary prevention in stable coronary artery disease. It has laid the groundwork to justify and guide the design of larger, more robust placebo- controlled Phase III trials. PROSPECTIVE STUDIES ON COLCHICINE IN PATIENTS UNDERGOING CORONARY ANGIOPLASTY AND STENTING Two prospective, randomized placebo-controlled trials examined the effects of colchicine on re-stenosis after coronary angioplasty. The first included 197 patients undergoing balloon angioplasty and showed that colchicine 0.6 mg BID