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New Data on Colchicine Bring Conflicting Results
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Karol E. Watson, MD, PhD, FACC, reviewing Nidorf SM et al. N Engl J Med 2020 Aug 31 Opstal TSJ et al. Circulation 2020 Aug 31 Tong DC et al. Circulation 2020 Aug 29
Colchicine shows positive cardiovascular results in one randomized, controlled study, neutral results in another, and worrisome noncardiovascular mortality data.
Inflammation promotes atherosclerosis and clinical events; thus, interest is growing in anti-inflammatory therapies for cardiovascular prevention. In 2019, the COLCOT trial (NEJM JW Cardiol Jan 2020 and N Engl J Med 2019; 381:2497) showed benefits of colchicine, a drug with anti-inflammatory properties, in patients with recent myocardial infarction (MI). Two randomized, controlled trials now evaluate colchicine in other patient populations.
Nidorf and colleagues (ACTRN12614000093684) studied colchicine (0.5 mg once daily) versus placebo in 5522 patients with chronic coronary artery disease (CAD; mean age, 66; 15% female). At a median follow-up of 29 months, the primary endpoint (composite of cardiovascular death, spontaneous [nonprocedural] MI, ischemic stroke, or ischemia-driven revascularization) was significantly lower in the colchicine group than in the placebo group (6.8% vs. 9.6%). Colchicine recipients also had a significantly lower rate of the key secondary endpoint (composite of cardiovascular death, spontaneous MI, or ischemic stroke) - 4.2% vs. 5.7%. No reduction in mortality was seen. In fact, the colchicine group had nominally more noncardiovascular deaths than the placebo group (53 and 35 deaths, respectively) and more all-cause deaths (73 and 60 deaths).
In a separate substudy, Opstal and colleagues performed targeted proteomic analysis on participants' serum samples before and after 30 days of colchicine treatment. Colchicine treatment was associated with a significant attenuation of the NLRP3 inflammasome pathway and with decreases in interleukin (IL)-18, IL-1 receptor antagonist, and IL-6.
Tong and colleagues (ACTRN12615000861550) evaluated colchicine versus placebo in 795 patients who presented with acute coronary syndrome (ACS) and had evidence of CAD (mean age, 60; 21% women). Colchicine dosing was 0.5 mg twice daily for the first month and then 0.5 mg once daily. At 12 months, the two groups did not differ significantly on the primary endpoint (composite of all-cause mortality, ACS, ischemia-driven [unplanned] urgent revascularization, and non-embolic ischemic stroke) - 6.1% in the colchicine group and 9.5% in the placebo group. However, significantly more colchicine patients died (8 vs. 1), driven largely by noncardiovascular deaths (5 vs. 0). Of the 8 patients who died, 5 had continued colchicine treatment until the time of death.
Comment
One trial showed cardiovascular benefit while the other was neutral for cardiovascular benefit, but both showed a consistent, worrisome result regarding noncardiovascular risks with colchicine, despite the studies' different populations, dosing regimens, and follow-up periods. The proteomics substudy confirms that colchicine attenuates inflammation. The studies highlight the complexity of inflammation and colchicine effects, but we need more data to truly understand the myriad effects of colchicine in cardiovascular disease.
Citation(s):
Nidorf SM et al. Colchicine in patients with chronic coronary disease. N Engl J Med 2020 Aug 31; [e-pub]. (https://doi.org/10.1056/NEJMoa2021372)
Opstal TSJ et al. Colchicine attenuates inflammation beyond the inflammasome in chronic coronary artery disease: A LoDoCo2 proteomic substudy. Circulation 2020 Aug 31; [e-pub]. (https://doi.org/10.1161/CIRCULATIONAHA.120.050560)
Tong DC et al. Colchicine in patients with acute coronary syndrome: The Australian COPS randomized clinical trial. Circulation 2020 Aug 29; [e-pub]. (https://doi.org/10.1161/CIRCULATIONAHA.120.050771)
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