■别嘌呤醇是一种黄嘌呤氧化酶抑制剂,可降低血清尿酸,用于预防痛风患者的急性痛风发作。观察性和小型干预性研究表明,别嘌呤醇对心血管有有益作用。
■确定别嘌呤醇是否能改善缺血性心脏病患者的主要心血管预后。
■预期,随机化,开放标签,盲化终点多中心临床试验。
■四百二十四个英国初级保健实践。
■60岁及以上患有缺血性心脏病,但没有痛风。
■使用中央基于网络的随机化系统对参与者进行随机化(1:1),接受每天600mg的别嘌呤醇,并添加到常规护理中或继续常规护理。
■主要结局是非致死性心肌梗死的复合结果,非致命性中风或心血管死亡。次要结局是非致死性心肌梗死,非致命性中风,心血管死亡,全因死亡率,因心力衰竭住院,急性冠脉综合征住院治疗,冠状动脉血运重建,急性冠状动脉综合征或冠状动脉血运重建住院治疗,所有的心血管住院,生活质量和成本效益。危险比(别嘌醇与在改良的意向治疗分析中评估Cox比例风险模型中的常规治疗)的优越性。
从2014年2月7日至2017年10月2日,5937名参与者被纳入并随机分配到别嘌呤醇组(n=2979)或常规护理组(n=2958)。共有5721名随机参与者(2853名别嘌醇;2868名常规治疗)被纳入改良的意向治疗分析人群(平均年龄72.0岁;75.5%为男性)。在主要终点,别嘌呤醇和常规护理组之间没有差异,别嘌醇组的314名(11.0%)参与者(每100个患者年2.47起事件)和常规护理组的325名(11.3%)参与者(每100个患者年2.37起事件),风险比1.04(95%置信区间0.89至1.21);p=0.65。98名(10.1%)的别嘌呤醇臂参与者和303名(10.6%)的常规护理臂参与者死亡,风险比1.02(95%置信区间0.87至1.20);p=0.77。如果主要终点没有统计学上的显著差异,则预先指定的健康经济分析计划是进行“试验内”成本效用分析。因此,NHS成本和质量调整后的生命年是在5年内估计的。别嘌醇治疗组之间的费用差异为+115英镑(95%置信区间为17英镑至210英镑),质量调整后的生命年没有差异(95%置信区间为-0.061至0.060)。我们得出的结论是,没有证据表明按照研究方案使用别嘌呤醇具有成本效益。
■结果可能无法推广到年轻人群,其他种族或患有更急性缺血性心脏病的患者。别嘌醇组的一千六百三十七名参与者(57.4%)退出了随机治疗,但是治疗中的分析给出了与主要分析相似的结果。
ALL-HEART研究表明,与常规治疗相比,每天600mg别嘌呤醇治疗缺血性心脏病患者并不能改善心血管预后。我们得出的结论是,在缺血性心脏病但无痛风的患者中,不建议将别嘌呤醇用于心血管事件的二级预防。
别嘌醇对缺血性心脏病和高尿酸血症或临床痛风患者心血管预后的影响可在未来的研究中探讨。
■该试验已注册为欧盟临床试验注册(EudraCT2013-003559-39)和ISRCTN(ISRCTN32017426)。
■该奖项由美国国家卫生与护理研究所(NIHR)卫生技术评估计划(NIHR奖参考:11/36/41)资助,并在《卫生技术评估》中全文发布。28号18.有关更多奖项信息,请参阅NIHR资助和奖励网站。
ALL-HEART研究的目的是确定对患有缺血性心脏病(通常也称为冠心病)的人给予别嘌呤醇是否会降低他们心脏病发作的风险。中风或死于心血管疾病。别嘌呤醇是一种通常给予痛风患者以防止急性痛风发作的药物。它目前不用于治疗缺血性心脏病。我们随机分配60岁以上的缺血性心脏病患者,每天服用600mg别嘌呤醇(除了他们的常规护理外)或继续他们的常规护理。然后,我们对参与者进行了几年的监测,并记录了任何重大的健康事件,如心脏病发作,中风和死亡。我们从中央持有的电子医院入院和死亡记录中获得了大部分随访数据,使研究对参与者来说更容易,更具成本效益。我们要求两组参与者完成问卷调查,以评估他们在研究期间的生活质量。我们还收集了数据,以确定在缺血性心脏病患者中使用别嘌呤醇对NHS是否有任何经济利益。心脏病发作的风险没有差异,给予别嘌呤醇的参与者与继续常规治疗的参与者之间的中风或心血管疾病死亡。我们还发现其他心血管事件的风险没有差异,任何原因导致的死亡或别嘌呤醇和常规护理组之间的生活质量测量。ALL-HEART研究的结果表明,我们不应该建议对缺血性心脏病患者给予别嘌呤醇,以防止进一步的心血管事件或死亡。
UNASSIGNED: Allopurinol is a xanthine oxidase inhibitor that lowers serum uric acid and is used to prevent acute gout flares in patients with gout. Observational and small interventional studies have suggested beneficial cardiovascular effects of allopurinol.
UNASSIGNED: To determine whether allopurinol improves major cardiovascular outcomes in patients with ischaemic heart disease.
UNASSIGNED: Prospective, randomised, open-label, blinded endpoint multicentre clinical trial.
UNASSIGNED: Four hundred and twenty-four UK primary care practices.
UNASSIGNED: Aged 60 years and over with ischaemic heart disease but no gout.
UNASSIGNED: Participants were randomised (1 : 1) using a central web-based randomisation system to receive allopurinol up to 600 mg daily that was added to usual care or to continue usual care.
UNASSIGNED: The primary outcome was the composite of non-fatal myocardial infarction, non-fatal stroke or cardiovascular death. Secondary outcomes were non-fatal myocardial infarction, non-fatal stroke, cardiovascular death, all-cause mortality, hospitalisation for heart failure, hospitalisation for acute coronary syndrome, coronary revascularisation, hospitalisation for acute coronary syndrome or coronary revascularisation, all cardiovascular hospitalisations, quality of life and cost-effectiveness. The hazard ratio (allopurinol vs. usual care) in a Cox proportional hazards model was assessed for superiority in a modified intention-to-treat analysis.
UNASSIGNED: From 7 February 2014 to 2 October 2017, 5937 participants were enrolled and randomised to the allopurinol arm (n = 2979) or the usual care arm (n = 2958). A total of 5721 randomised participants (2853 allopurinol; 2868 usual care) were included in the modified intention-to-treat analysis population (mean age 72.0 years; 75.5% male). There was no difference between the allopurinol and usual care arms in the primary endpoint, 314 (11.0%) participants in the allopurinol arm (2.47 events per 100 patient-years) and 325 (11.3%) in the usual care arm (2.37 events per 100 patient-years), hazard ratio 1.04 (95% confidence interval 0.89 to 1.21); p = 0.65. Two hundred and eighty-eight (10.1%) participants in the allopurinol arm and 303 (10.6%) participants in the usual care arm died, hazard ratio 1.02 (95% confidence interval 0.87 to 1.20); p = 0.77. The pre-specified health economic analysis plan was to perform a \'within trial\' cost-utility analysis if there was no statistically significant difference in the primary endpoint, so NHS costs and quality-adjusted life-years were estimated over a 5-year period. The difference in costs between treatment arms was +£115 higher for allopurinol (95% confidence interval £17 to £210) with no difference in quality-adjusted life-years (95% confidence interval -0.061 to +0.060). We conclude that there is no evidence that allopurinol used in line with the study protocol is cost-effective.
UNASSIGNED: The results may not be generalisable to younger populations, other ethnic groups or patients with more acute ischaemic heart disease. One thousand six hundred and thirty-seven participants (57.4%) in the allopurinol arm withdrew from randomised treatment, but an on-treatment analysis gave similar results to the main analysis.
UNASSIGNED: The ALL-HEART study showed that treatment with allopurinol 600 mg daily did not improve cardiovascular outcomes compared to usual care in patients with ischaemic heart disease. We conclude that allopurinol should not be recommended for the secondary prevention of cardiovascular events in patients with ischaemic heart disease but no gout.
UNASSIGNED: The effects of allopurinol on cardiovascular outcomes in patients with ischaemic heart disease and co-existing hyperuricaemia or clinical gout could be explored in future studies.
UNASSIGNED: This trial is registered as EU Clinical Trials Register (EudraCT 2013-003559-39) and ISRCTN (ISRCTN 32017426).
UNASSIGNED: This award was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme (NIHR award ref: 11/36/41) and is published in full in Health Technology Assessment; Vol. 28, No. 18. See the NIHR Funding and Awards website for further award information.
The purpose of the ALL-HEART study was to determine whether giving allopurinol to people with ischaemic heart disease (also commonly known as coronary heart disease) would reduce their risk of having a heart attack, stroke or of dying from cardiovascular disease. Allopurinol is a medication usually given to patients with gout to prevent acute gout flares. It is not currently used to treat ischaemic heart disease. We randomly allocated people aged over 60 years with ischaemic heart disease to take up to 600 mg of allopurinol daily (in addition to their usual care) or to continue with their usual care. We then monitored participants for several years and recorded any major health events such as heart attacks, strokes and deaths. We obtained most of the follow-up data from centrally held electronic hospital admissions and death records, making the study easier for participants and more cost-efficient. We asked participants in both groups to complete questionnaires to assess their quality of life during the study. We also collected data to determine whether there was any economic benefit to the NHS of using allopurinol in patients with ischaemic heart disease. There was no difference in the risk of heart attacks, strokes or death from cardiovascular disease between the participants given allopurinol and those in the group continuing their usual care. We also found no difference in the risks of other cardiovascular events, deaths from any cause or quality-of-life measurements between the allopurinol and usual care groups. The results of the ALL-HEART study suggest that we should not recommend that allopurinol be given to people with ischaemic heart disease to prevent further cardiovascular events or deaths.