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Increased mortality with colchicine in patients with ACS

Presented By
Prof. Jamie Layland , Monash University, Australia
Conference
ESC 2020
Trial
COPS trial

The Australian COPS trial demonstrated that the addition of colchicine to standard medical therapy did not significantly affect cardiovascular outcomes at 12 months in patients with acute coronary syndromes (ACS). Colchicine may even be associated with a higher rate of mortality in this patient population [1,2].

Inflammation plays a crucial role in atherosclerosis and ultimately may contribute to the ongoing complications of ACS. The recently published CANTOS trial demonstrated that treatment with the interleukin (IL)-1β inhibitor canakinumab resulted in a reduction in cardiovascular events in ACS patients [3]. Because of its anti-inflammatory properties, colchicine, a commonly used treatment for gout, has recently emerged as a promising novel treatment option for cardiovascular disease. The proposed mechanisms of action of colchicine involve inhibition of innate immunity and modulation of downstream inflammatory cascades, which are pivotal processes involved in the pathogenesis of coronary artery disease (CAD) and thrombotic events of ACS. The previously published COLCOT and LoDoCo trials demonstrated a significant reduction in adverse cardiovascular events in patients with ACS and stable CAD who received colchicine in addition to standard secondary prevention therapies compared with standard medical therapy alone [4,5].

Prof. Jamie Layland (Monash University, Australia) presented the results of the COPS study, which evaluated the potential clinical utility of colchicine among a broad ACS population (n=795) [1]. The primary outcome was a composite of all-cause mortality, ACS, ischaemia-driven (i.e. unplanned) urgent revascularisation, and non-cardioembolic ischaemic stroke.

Over the 12-month follow-up period, there were 24 events in the colchicine group (n=396) compared with 38 events in the placebo group (n=399) (P=0.09). There was a higher rate of total death (8 vs 1; P=0.017) and particularly non-cardiovascular death in the colchicine group (5 vs 0; P=0.024). The rates of reported adverse events were not different (colchicine 23.0% vs placebo 24.3%) and predominantly gastrointestinal (colchicine 23.0% vs placebo 20.8%).

In conclusion, the addition of colchicine to standard medical therapy in the COPS trial did not significantly affect cardiovascular outcomes at 12 months in an ACS population and was associated with a higher rate of mortality. Despite these results, exploratory analysis suggested a potential role for colchicine to improve cardiovascular outcomes. Further clinical research is required before colchicine can be safely administered in ACS patients.

 

    1. Layland J. COPS Trial – Colchicine to improve cardiovascular outcomes in ACS patients. Late-Breaking Science, ESC Congress 2020, 29 Aug.
    2. Tong DC, et al. Circulation 2020, 29 Aug.
    3. Ridker PM, et al. Am Heart J. 2011 Oct;162(4):597-605.
    4. Tardif J-C, et al. N Engl J Med 2019; 381:2497-2505.
    5. Nidorf SM, et al. J Am Coll Cardiol. 2013; 61(4):404-410.

 



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