《柳叶刀》2017年6月13日在线先发

http://thelancet.com/journals/lancet/article/PIIS0140-6736(17)30770-5/fulltext

血管事件后长期抗血小板治疗出血的年龄特异性风险、严重性、时间进程及转归：一项基于人群的队列研究

背景

基于主要在年龄小于75岁的患者中进行的临床试验，推荐缺血性血管事件后应进行终身抗血小板治疗，在阿司匹林的临床试验中，上消化道出血是一种严重并发症，但死亡率低，通常认为不会引起长期残疾。因此，尽管同时开具质子泵抑制剂（PPIs）处方可以减少70-90%的上消化道出血，但这样联用者少，且指南也有自相矛盾。为此，我们在所有老年患者中旨在评价进行二级预防的抗血小板治疗的出血风险、出血时间进程及出血转归。

方法

2002-2012年进行的“牛津血管研究”出现终点事件后，随访至2013年，对首次一过性脑缺血发作、缺血性脑卒中或心肌梗塞进行抗血小板药物（主要为阿司匹林，未常规使用质子泵抑制剂）治疗的患者，我们进行了一项基于人群的前瞻性队列研究。我们对通过面对面随访需要就医的出血类型、严重程度、转归（致残或死亡）以及出血的时间进程进行了10年的研究，在Kaplan–Meier风险估算的基础上，对于常规同时开具质子泵抑制剂处方预防上消化道出血，我们估算了年龄特异性的需治数（NNT）（NNT是指防止1例不良事件发生或得到1例有利结果需要治疗的病例数——译者注），且从既往的临床试验中估算出风险下降的相对估测值。

结果

在13509患者年的随访期间，3166名患者（年龄≥75岁1582名[50%]）有405个首次出血事件（胃肠出血n=218，颅内出血n=45，其它出血n=142）。收住院的314名（78%）出血患者中，117名（37%）因行政编码而失访。不是大出血的出血风险与年龄不相关，但大出血随着年龄的增长急剧上升（≥75的风险比[HR]，3.10；95%CI，2.27-4.24；p<0.0001），特别是致命性出血（5.53，2.65–11.54；p<0.0001），且在长期随访期间持续如此；上消化道大出血亦如此（≥75岁的风险比，4.13，2.60-6.57；p<0.0001），特别是有致残或致命性大出血时（10.26，4.37–24.13；p<0.0001）。年龄≥75岁时，上消化道大出血大多是致残性或致命性的（73名患者中有45名[62%]，对比213名复发性缺血性脑卒中患者中有101名[47%]），上消化道大出血数量超过了致残性或致死性的颅内出血数量（n=45对比n=18），绝对风险值为每1000患者年9.15（95%CI，6.67–12.24）。常规使用质子泵抑制剂预防5年期间1次致残性或致命性上消化道出血所估算出的需治数下降， 65岁以下者需治数为338，到≥85岁者需治数为25。

解释

在接受以阿司匹林打底的抗血小板治疗、且未常规使用质子泵抑制剂的患者中，高龄患者大出血的长期风险及这种风险持续时间实际上高于既往临床试验中的较年轻患者，且致残性或致死性上消化道出血的风险巨大。考虑到≥75岁患者中半数大出血为上消化道出血，常规使用质子泵抑制剂预防这类出血的估算需治数小，因此（对这类患者进行抗血小板治疗时）应当鼓励同时开具质子泵抑制剂处方。

《壹篇》南南和北北

Age-specific risks, severity, time course, and outcome of bleeding on long-term antiplatelet treatment after vascular events: a population-based cohort study

Background

Lifelong antiplatelet treatment is recommended after ischaemic vascular events, on the basis of trials done mainly in patients younger than 75 years. Upper gastrointestinal bleeding is a serious complication, but had low case fatality in trials of aspirin and is not generally thought to cause long-term disability. Consequently, although co-prescription of proton-pump inhibitors (PPIs) reduces upper gastrointestinal bleeds by 70–90%, uptake is low and guidelines are conflicting. We aimed to assess the risk, time course, and outcomes of bleeding on antiplatelet treatment for secondary prevention in patients of all ages.

Methods

We did a prospective population-based cohort study in patients with a first transient ischaemic attack, ischaemic stroke, or myocardial infarction treated with antiplatelet drugs (mainly aspirin based, without routine PPI use) after the event in the Oxford Vascular Study from 2002 to 2012, with follow-up until 2013. We determined type, severity, outcome (disability or death), and time course of bleeding requiring medical attention by face-to-face follow-up for 10 years. We estimated age-specific numbers needed to treat (NNT) to prevent upper gastrointestinal bleeding with routine PPI co-prescription on the basis of Kaplan–Meier risk estimates and relative risk reduction estimates from previous trials.

Findings

3166 patients (1582 [50%] aged ≥75 years) had 405 first bleeding events (n=218 gastrointestinal, n=45 intracranial, and n=142 other) during 13?509 patient-years of follow-up. Of the 314 patients (78%) with bleeds admitted to hospital, 117 (37%) were missed by administrative coding. Risk of non-major bleeding was unrelated to age, but major bleeding increased steeply with age (≥75 years hazard ratio [HR] 3·10, 95% CI 2·27–4·24; p<0·0001), particularly for fatal bleeds (5·53, 2·65–11·54; p<0·0001), and was sustained during long-term follow-up. The same was true of major upper gastrointestinal bleeds (≥75 years HR 4·13, 2·60–6·57; p<0·0001), particularly if disabling or fatal (10·26, 4·37–24·13; p<0·0001). At age 75 years or older, major upper gastrointestinal bleeds were mostly disabling or fatal (45 [62%] of 73 patients vs 101 [47%] of 213 patients with recurrent ischaemic stroke), and outnumbered disabling or fatal intracerebral haemorrhage (n=45 vs n=18), with an absolute risk of 9·15 (95% CI 6·67–12·24) per 1000 patient-years. The estimated NNT for routine PPI use to prevent one disabling or fatal upper gastrointestinal bleed over 5 years fell from 338 for individuals younger than 65 years, to 25 for individuals aged 85 years or older.

Interpretation

In patients receiving aspirin-based antiplatelet treatment without routine PPI use, the long-term risk of major bleeding is higher and more sustained in older patients in practice than in the younger patients in previous trials, with a substantial risk of disabling or fatal upper gastrointestinal bleeding. Given that half of the major bleeds in patients aged 75 years or older were upper gastrointestinal, the estimated NNT for routine PPI use to prevent such bleeds is low, and co-prescription should be encouraged.

Funding

Wellcome Trust, Wolfson Foundation, British Heart Foundation, Dunhill Medical Trust, National Institute of Health Research (NIHR), and the NIHR Oxford Biomedical Research Centre.

《壹篇》系主要面向医务人员的公益性头条号，不以营利为目的，不进行任何有偿咨询和服务，不出售任何产品，与ASCO、CSCO等所有专业学会和机构没有任何关系和联系，也不代表任何官方学会发声。

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