Dawson Jesse, Robertson Michele, Dickie David Alexander, Bath Phillip, Forbes Kirsten, Quinn Terence, Broomfield Niall M, Dani Krishna, Doney Alex, Houston Graeme, Lees Kennedy R, Muir Keith W, Struthers Allan, Walters Matthew, Barber Mark, Bhalla Ajay, Cameron Alan, Dyker Alexander, Guyler Paul, Hassan Ahamad, Kearney Mark T, Keegan Breffni, Lakshmanan Sekaran, Macleod Mary Joan, Randall Marc, Shaw Louise, Subramanian Ganesh, Werring David, McConnachie Alex
School of Cardiovascular and Metabolic Health, College of Medical, Veterinary & Life Sciences, University of Glasgow, Queen Elizabeth University Hospital, Glasgow, G51 4TF, UK.
Robertson Centre for Biostatistics, School of Health and Wellbeing, College of Medical, Veterinary & Life Sciences, University of Glasgow, Glasgow, G12 8QQ, UK.
EClinicalMedicine. 2023 Feb 16;57:101863. doi: 10.1016/j.eclinm.2023.101863. eCollection 2023 Mar.
People who experience an ischaemic stroke are at risk of recurrent vascular events, progression of cerebrovascular disease, and cognitive decline. We assessed whether allopurinol, a xanthine oxidase inhibitor, reduced white matter hyperintensity (WMH) progression and blood pressure (BP) following ischaemic stroke or transient ischaemic attack (TIA).
In this multicentre, prospective, randomised, double-blinded, placebo-controlled trial conducted in 22 stroke units in the United Kingdom, we randomly assigned participants within 30-days of ischaemic stroke or TIA to receive oral allopurinol 300 mg twice daily or placebo for 104 weeks. All participants had brain MRI performed at baseline and week 104 and ambulatory blood pressure monitoring at baseline, week 4 and week 104. The primary outcome was the WMH Rotterdam Progression Score (RPS) at week 104. Analyses were by intention to treat. Participants who received at least one dose of allopurinol or placebo were included in the safety analysis. This trial is registered with ClinicalTrials.gov, NCT02122718.
Between 25th May 2015 and the 29th November 2018, 464 participants were enrolled (232 per group). A total of 372 (189 with placebo and 183 with allopurinol) attended for week 104 MRI and were included in analysis of the primary outcome. The RPS at week 104 was 1.3 (SD 1.8) with allopurinol and 1.5 (SD 1.9) with placebo (between group difference -0.17, 95% CI -0.52 to 0.17, p = 0.33). Serious adverse events were reported in 73 (32%) participants with allopurinol and in 64 (28%) with placebo. There was one potentially treatment related death in the allopurinol group.
Allopurinol use did not reduce WMH progression in people with recent ischaemic stroke or TIA and is unlikely to reduce the risk of stroke in unselected people.
The British Heart Foundation and the UK Stroke Association.
经历过缺血性中风的人有复发血管事件、脑血管疾病进展和认知衰退的风险。我们评估了黄嘌呤氧化酶抑制剂别嘌醇是否能减少缺血性中风或短暂性脑缺血发作（TIA）后的白质高信号（WMH）进展和血压（BP）。
在英国22个中风单元进行的这项多中心、前瞻性、随机、双盲、安慰剂对照试验中，我们将缺血性中风或TIA发生后30天内的参与者随机分配，使其接受每日两次口服300毫克别嘌醇或安慰剂，为期104周。所有参与者在基线和第104周时进行脑部MRI检查，并在基线、第4周和第104周时进行动态血压监测。主要结局是第104周时的WMH鹿特丹进展评分（RPS）。分析采用意向性治疗。接受至少一剂别嘌醇或安慰剂的参与者纳入安全性分析。本试验已在ClinicalTrials.gov注册，注册号为NCT02122718。
在2015年5月25日至2018年11月29日期间，共招募了464名参与者（每组232名）。共有372名（189名服用安慰剂，183名服用别嘌醇）参与者接受了第104周的MRI检查，并纳入主要结局分析。别嘌醇组第104周的RPS为1.3（标准差1.8），安慰剂组为1.5（标准差1.9）（组间差异-0.17，95%置信区间-0.52至0.17，p=0.33）。服用别嘌醇的参与者中有73名（32%）报告了严重不良事件，服用安慰剂的参与者中有64名（28%）报告了严重不良事件。别嘌醇组有1例可能与治疗相关的死亡。
对于近期缺血性中风或TIA患者，使用别嘌醇并不能减少WMH进展，且不太可能降低未经选择人群的中风风险。
英国心脏基金会和英国中风协会。
