Cardiovascular events in gout patients starting urate-lowering therapy with or without colchicine for flare prophylaxis: a 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 Starting urate-lowering therapy (ULT) may trigger gout flares. Gout flares have been temporally associated with an increased risk of cardiovascular events (CVEs).
Objective To estimate the risk of CVEs among patients with gout initiating ULT with flare prophylaxis using colchicine compared to no prophylaxis.
Methods We performed a new-user cohort study using data from the CPRD Aurum, an English primary-care database linked to hospitalisation and mortality records. People with gout starting ULT for the first time were eligible for inclusion. Colchicine prophylaxis (defined as prescription ≥21 days in length) prescribed on the same date as ULT was the exposure of interest. A composite of fatal and non-fatal myocardial infarction or stroke was the outcome of interest. Patients were followed up to 180 days after ULT initiation.
Propensity score overlap weighting was used to balance covariates across study arms. 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%CI. Members of The UK Gout Society were involved in prioritising the research question.
Results We ascertained 99,800 gout patients initiating ULT (25,511 (25.6%) and 74,289 (74.4%) of 99,800 patients were female and male, respectively, the mean (SD) age was 62.5 (15.5) years, and 84,928 (85.1%) of 99,800 patients were White). 4,063 (4.1%) of 99,800 patients had prior CVEs and 16,028 (16%) of 99,800 patients were prescribed colchicine prophylaxis. Patients with colchicine prophylaxis had significantly lower risk of CVEs compared with those without prophylaxis. The weighted rates of CVEs were 28.8/1,000 person-years (95%CI:25.2-33.2) and 35.3 (95%CI:33.0-37.9) in patients with colchicine prophylaxis and those without prophylaxis, respectively (weighted rate difference -6.5 (95%CI:-9.4 to -3.6)/1,000 person-years and weighted hazard ratio 0.82 (95%CI:0.69-0.94) in the intention-to-treat analysis. Findings were similar across analytical approaches, stratified analyses, and for secondary outcomes.
Conclusion Among gout patients initiating ULT, the risk of CVEs was reduced in those prescribed colchicine prophylaxis compared with no prophylaxis. These findings provide an additional argument for using colchicine for gout flare prophylaxis.

Citation

CIPOLLETTA, E., Nakafero, G., McCormick, N., Yokose, C., Avery, A., Mamas, M., Choi, H., Tata, L., & Abhishek, A. (in press). Cardiovascular events in gout patients starting urate-lowering therapy with or without colchicine for flare prophylaxis: a new-user cohort study using linked primary care, hospitalisation and mortality data. The Lancet Rheumatology,

• Journal Article Type: Article
• Acceptance Date: Aug 9, 2024
• Deposit Date: Aug 23, 2024
• Journal: The Lancet Rheumatology
• Electronic ISSN: 2665-9913
• Publisher: Elsevier
• Peer Reviewed: Peer Reviewed
• Keywords: Flare prophylaxis, urate-lowering therapy, cardiovascular events, myocardial infarction, stroke, gout, gout flares
• Public URL: https://nottingham-repository.worktribe.com/output/38646687