Op0136 Risk of Cardiovascular Events in Patients With Gout Starting Urate-Lowering Therapy With or Without Flare Prophylaxis With Colchicine: An Emulated Target Trial Using English Primary-Care, Hospitalisation, and Mortality Data

Background: Gout flares are associated with cardiovascular events (CVEs). Clinical trials show that low-dose colchicine reduces the risk of CVEs in patients with atherosclerotic cardiovascular diseases [1,2]. An observational study reported an increased risk of myocardial infarction (MI) in people with gout starting urate-lowering therapy (ULT) co-prescribed with colchicine [3]. Objectives: To estimate the risk of CVEs among patients with gout initiating ULT with colchicine flare prophylaxis defined as a prescription for at least 21 days compared with no flare prophylaxis. Methods: English patients with a new diagnosis of gout starting ULT for the first time were included in a new-user cohort study using an emulated target trial design. Patients co-prescribed colchicine for ≥21 days on the same date as ULT initiation were compared with patients not prescribed colchicine or NSAIDs for ≥21 days on the same date as ULT initiation. Outcomes. First CVE (fatal and non-fatal stroke or MI) after cohort entry. Secondary outcomes. First-ever CVE, fatal CVE, MI, and stroke. Negative control outcomes: respiratory tract infections, peptic ulcer disease. Positive control outcome: diarrhoea. Follow-up. We performed intention-to-treat (ITT) and per-protocol (PP) analyses. In ITT, follow up was from ULT initiation to 180 days. In PP, follow-up was censored earlier if exposed patients ended prophylaxis, switched to NSAID prophylaxis, or if controls were prescribed prophylaxis. Statistical analysis. We used Cox proportional hazards models to obtain adjusted hazard ratios (aHR). We calculated adjusted incidence rates (aIR), adjusted risk differences (aRD). In the PP analyses, inverse probability of censoring weighting was applied. Results: 99,800 patients were included (Figure 1): mean (standard deviation (SD)) age 62.8 (15.5) years, 25,511 (25.6%) female, 4,063 (4.1%) with prior CVE, median (interquartile range (IQR)) disease duration 0.2 years (0-2.4) and mean (SD) serum urate 516.4 micromol/l (94.1). Nearly all patients started allopurinol (99.3%). Controls and exposed patients were followed-up for 176.9 (26.7) and 175.5 (29.7) days in the ITT analysis and 161.1 (49.5) and 45.7 (33.1) days in PP analysis. Patients with colchicine prophylaxis had lower risks of CVEs compared to those without prophylaxis in both the ITT (aHR: 0.82, 95%CI: 0.69-0.94, aRD: -6.5/1,000 person-years (95%CI: -9.4 to -3.6) and PP analyses (aHR: 0.79, 95%CI: 0.58-0.99, aRD: -3.9/1,000 person-years (95%CI:-7.1 to -0.7) (Table 1). The protective effect was present across a range of stratified analyses (i.e. age, gender, cardiovascular risk category, and year of ULT initiation). Colchicine prophylaxis was not associated with negative control outcomes. Conclusion: Colchicine prophylaxis was associated with a reduced risk of CVEs when initiating ULT. REFERENCES: [1] 10.1056/NEJMoa1912388. [2] 10.1056/NEJMoa2021372. [3] 10.1136/ard-2023-224154. Acknowledgements: This project has been funded by the Foundation for Research in Rheumatology (FOREUM). Disclosure of Interests: Edoardo Cipolletta has received consulting fees from Horizon Therapeutics outside the submitted work and lecturing fees from Novartis outside the submitted work., Georgina Nakafero: None declared, Anthony Avery: None declared, Mamas Mamas: None declared, Laila Tata: None declared, Abhishek Abhishek: None declared.