Colchicine Prophylaxis for Gout Flares Linked to Lower Cardiovascular Events

Edoardo Cipoletta, MD

Credit: ResearchGate

Prophylactic colchicine reduced the risk of cardiovascular events in patients with gout initiating urate-lowering therapy compared to those not prescribed prophylactic colchicine.¹

Lead investigator Edoardo Cipolletta, MD, Academic Rheumatology, School of Medicine, Nottingham City Hospital, University of Nottingham, United Kingdom, and colleagues conducted a retrospective new-user cohort study using data from the Clinical Practice Research Datalink Aurum, an English primary-care database linked to hospitalization and mortality records. The study included people with gout initiating urate-lowering therapy for the first time and compared people prescribed flare prophylaxis with colchicine with those not prescribed any gout flare prophylaxis.

“Cipolletta and colleagues propose the prevention of gout flare as an additional cause of the beneficial effect of colchicine on cardiovascular event risk. Gout flares have been associated with an increase in cardiovascular events, albeit transient, following flare. One can speculate whether this effect is additional to or part of a more general colchicine effect on the chronic inflammatory state that is supposedly present in all patients with gout, also between flares,” Hein Janssens, MD, PhD, Department of Primary and Community Care, Radboudumc Research Institute for Medical Innovation, Radboud University Medical Centre, Nijmegen 6500, Netherlands, and Matthijs Janssen, MD, PhD, Department of Rheumatology, VieCuri Medical Centre, Venlo, Netherlands, wrote in a related editorial.² “This gout inflammatory state has been suggested to have a link with increased cardiovascular event risks similar to rheumatoid arthritis and in accordance with circulating proinflammatory cytokines associated with monosodium urate crystal depositions and cardiovascular events.”

Cipoletta and colleagues included 99,800 patients with gout initiating urate-lowering therapy in the study, 25,511 (25.6%) of which were female and 84,928 (85.1%) of which were White. Participants had a mean age of 62.8 years (standard deviation [SD], 15.5), 4063 (4.1%) patients had previous cardiovascular events and 16,028 (16.1%) were prescribed colchicine prophylaxis.¹

The investigators found that patients prescribed colchicine prophylaxis had a significantly lower risk of cardiovascular events compared with those without, with weighted rates of cardiovascular events of 28.8 per 1000 person-years (95% CI, 25.2-33.2) and 35.3 per 1000 person-years (95% CI, 33.0-37.9), respectively. These rates translate to a weighted rate difference of –6·5 [95% CI, –9·4 to –3·6] per 1000 person-years and a weighted hazard ratio of 0.82 [95% CI, 0.69–0.94] in patients with prophylactic colchicine in the intent-to-treat analysis. These findings were supported by further, stratified analyses, and for secondary outcomes.¹

“Let the findings in this robust, high-quality observational study be the invitation for gout researchers to design a randomized controlled trial to confirm them. After all, the observed beneficial effect of colchicine concerns a huge group of patients worldwide,” Janssens and Janssen wrote.² “In addition, it is conceivable that, if a cardiovascular risk reduction is indeed confirmed, a strong argument arises to recommend the prescription of a course of colchicine to all (flaring) patients with gout, independently of their preference for urate-lowering therapy in general or urate-lowering therapy with or without colchicine prophylaxis more specifically.”

REFERENCES
1. Cipoletta E, Nakafero G, McCormick N, et al. Cardiovascular events in patients with gout initiating urate-lowering therapy with or without colchicine for flare prophylaxis: a retrospective new-user cohort study using linked primary care, hospitalisation, and mortality data. Lancet Rheumatol. Published online December 18, 2024. doi: 10.1016/S2665-9913(24)00248-0

2. Janssens H, Janssen M. Beneficial side-effects of colchicine for patients with gout. Lancet Rheumatol. Published online December 18, 2024.