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

Cipolletta, Edoardo; Nakafero, Georgina; McCormick, Natalie; Yokose, Chio; Avery, Anthony; Mamas, Mamas; Choi, Hyon; Tata, Laila; Abhishek, Abhishek

Abstract

Background
Initiating urate-lowering therapy can trigger gout flares. Gout flares have been associated with a temporally increased risk of cardiovascular events. Therefore, we aimed to estimate the risk of cardiovascular events in patients with gout initiating urate-lowering therapy with flare prophylaxis using colchicine (the drug recommended for gout flare prohphylaxis by many international societies) compared with no prophylaxis.

Methods
We did a retrospective new-user cohort study using data from the Clinical Practice Research Datalink Aurum, an English primary-care database linked to hospitalisation and mortality records. People with gout initiating urate-lowering therapy for the first time were eligible for inclusion. We compared people prescribed flare prophylaxis with colchicine with those not prescribed any gout flare prophylaxis. Colchicine prophylaxis (defined as prescription for ≥21 days) prescribed on the same date as urate-lowering therapy was the exposure of interest. A composite of fatal and non-fatal myocardial infarction or stroke within 180 days after urate-lowering therapy initiation regardless of any previous cardiovascular event was the primary outcome. Propensity score overlap weighting was used to balance covariates across study groups. We used Cox regression and performed intention-to-treat and per-protocol analyses, the latter with an inverse probability of censoring weighting. The association was measured using hazard ratio and risk difference with 95% CIs. Members of The UK Gout Society were involved in prioritising the research question.

Findings
Of the 111 460 patients eligible for the study, 99 800 patients with gout initiating urate-lowering therapy were included. 25 511 (25·6%) of 99 800 patients were female, 74 289 (74·4%) were male, 84 928 (85·1%) patients were White and the mean age was 62·8 years (SD 15·5). 4063 (4·1%) patients had previous cardiovascular events and 16 028 (16·1%) patients were prescribed colchicine prophylaxis. Patients with colchicine prophylaxis had significantly lower risk of cardiovascular events compared with those without prophylaxis. The weighted rates of cardiovascular events were 28·8 per 1000 person-years (95% CI 25·2 to 33·2) in patients with colchicine prophylaxis and 35·3 per 1000 person-years (33·0 to 37·9) in those without prophylaxis (weighted rate difference –6·5 [95% CI –9·4 to –3·6] per 1000 person-years and weighted hazard ratio 0·82 [0·69–0·94]) in the intention-to-treat analysis. Findings were similar across analytical approaches, stratified analyses, and for secondary outcomes.

Interpretation
In patients with gout initiating urate-lowering therapy, the risk of cardiovascular events was reduced in those prescribed colchicine prophylaxis compared with no prophylaxis. These findings provide an additional argument for using colchicine for gout flare prophylaxis.

Funding
Foundation for Research in Rheumatology.

Citation

Cipolletta, E., Nakafero, G., McCormick, N., Yokose, C., Avery, A., Mamas, M., Choi, H., Tata, L., & Abhishek, A. (2024). 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. The Lancet Rheumatology, https://doi.org/10.1016/S2665-9913%2824%2900248-0

• Journal Article Type: Article
• Acceptance Date: Aug 9, 2024
• Online Publication Date: Dec 18, 2024
• Publication Date: Dec 18, 2024
• Deposit Date: Aug 23, 2024
• Publicly Available Date: Aug 23, 2024
• Journal: The Lancet Rheumatology
• Electronic ISSN: 2665-9913
• Publisher: Elsevier
• Peer Reviewed: Peer Reviewed
• DOI: https://doi.org/10.1016/S2665-9913%2824%2900248-0
• Keywords: Flare prophylaxis, urate-lowering therapy, cardiovascular events, myocardial infarction, stroke, gout, gout flares
• Public URL: https://nottingham-repository.worktribe.com/output/38646687
• Publisher URL: https://www.thelancet.com/journals/lanrhe/article/PIIS2665-9913(24)00248-0/fulltext