アブストラクト | 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. |
投稿者 | Cipolletta, Edoardo; Nakafero, Georgina; McCormick, Natalie; Yokose, Chio; Avery, Anthony J; Mamas, Mamas A; Choi, Hyon K; Tata, Laila J; Abhishek, Abhishek |
組織名 | Academic Rheumatology, School of Medicine, Nottingham City Hospital, University;of Nottingham, Nottingham, UK; Rheumatology Unit, Department of Clinical and;Molecular Sciences, Polytechnic University of Marche, Ancona, Italy. Electronic;address: msaec14@exmail.nottingham.ac.uk.;of Nottingham, Nottingham, UK.;Rheumatology & Allergy Clinical Epidemiology Research Center, The Mongan;Institute, Department of Medicine, Massachusetts General Hospital, Boston, MA,;USA; Division of Rheumatology, Allergy, and Immunology, Department of Medicine,;Massachusetts General Hospital, Boston, MA, USA; Harvard Medical School, Boston,;MA, USA; Arthritis Research Canada, Vancouver, BC, Canada.;MA, USA.;Centre for Academic Primary Care, School of Medicine, University of Nottingham,;Nottingham, UK.;Keele Cardiovascular Research Group, Keele University, Keele, UK; National;Institute for Health and Care Research Birmingham Biomedical Research Centre,;Birmingham, UK.;Lifespan and Population Health Unit, School of Medicine, University of;Nottingham, Nottingham, UK.;of Nottingham, Nottingham, UK; National Institute for Health and Care Research;Nottingham Biomedical Research Centre, University of Nottingham, Nottingham, UK. |