英国诺丁汉大学Chris Hawkey团队研究了根除幽门螺杆菌对初级保健中使用阿司匹林的老年患者消化性溃疡出血的一级预防效果。2022年11月5日出版的《柳叶刀》杂志发表了这项成果。

服用阿司匹林患者的消化性溃疡与幽门螺杆菌感染有关。该研究旨在探讨根除幽门螺杆菌是否能预防阿司匹林相关溃疡出血。

研究组使用常规收集的临床数据，在英国1208家初级保健中心进行了一项随机、双盲、安慰剂对照试验（根除幽门螺杆菌阿司匹林试验[HEAT]）。符合条件的患者年龄为60岁及以上，每天服用325 mg或更少的阿司匹林（过去一年中有4次或更多28天处方），并且在筛查时对幽门螺杆菌的C13尿素呼气试验呈阳性。接受溃疡或胃保护药物治疗的患者被排除在外。

参与者被随机分配（1:1）接受口服克拉霉素500 mg、甲硝唑400 mg和兰索拉唑30 mg的联合治疗（积极根除），或口服安慰剂（对照），每日两次，持续1周。参与者、他们的全科医生和医疗保健提供者、研究护士、试验团队、裁决委员会和分析团队在整个试验过程中都双盲。随访是对初级和次级保健中的电子数据进行审查。主要结局是因明确或可能的消化性溃疡出血而住院或死亡的时间，并在意向治疗人群中采用Cox比例风险法进行分析。

2012年9月14日至2017年11月22日，30166名患者进行了幽门螺杆菌呼气试验，5367名患者结果为阳性，5352名患者被随机分为积极根除组（2677例）或安慰剂组（2775例），并进行了5.0年的中位随访。对主要结局的分析表明，该结果与比例风险假设存在显著差异，需要在不同的时间段进行分析。

与对照组相比，积极根除组在最初2.5年随访中主要结局的发生率显著降低（6次被判定为明确或可能的消化性溃疡出血，发生率为每1000人-年0.92；对照组有17次，发生率为每1000人-年2.61；危险比为0.35）。在校正了竞争性死亡风险后，这一优势仍然显著，但随着随访时间的延长，这种优势消失了（在最初的2.5年后HR为1.31）。研究组积极征求不良事件报告；其中味觉障碍是最常见的事件（787例患者）。

研究结果表明，根除幽门螺杆菌可以预防阿司匹林相关的消化性溃疡出血，但这可能不会长期持续下去。

附：英文原文

Title: Helicobacter pylori eradication for primary prevention of peptic ulcer bleeding in older patients prescribed aspirin in primary care (HEAT): a randomised, double-blind, placebo-controlled trial

Author: Chris Hawkey, Anthony Avery, Carol A C Coupland, Colin Crooks, Jennifer Dumbleton, F D Richard Hobbs, Denise Kendrick, Michael Moore, Clive Morris, Gregory Rubin, Murray Smith, Diane Stevenson, David CA Mant, Alexander C Ford, Thomas M Macdonald, Mike Bradburn, Claire A Klauza, Angela Shone, Richard FA Logan, Jonathan J Deeks, Kenneth E.L. McColl, Andrew F Goddard, Richard Stevens, Sarned Sami, John Haughney, Margaret E Cupples, Monique Morar, Wendy OBrien

Issue&Volume: 2022/11/05

Abstract:

Background

Peptic ulcers in patients receiving aspirin are associated with Helicobacter pylori infection. We aimed to investigate whether H pylori eradication would protect against aspirin-associated ulcer bleeding.

Methods

We conducted a randomised, double-blind, placebo-controlled trial (Helicobacter Eradication Aspirin Trial [HEAT]) at 1208 primary care centres in the UK, using routinely collected clinical data. Eligible patients were aged 60 years or older who were receiving aspirin at a daily dose of 325 mg or less (with four or more 28-day prescriptions in the past year) and had a positive C13 urea breath test for H pylori at screening. Patients receiving ulcerogenic or gastroprotective medication were excluded. Participants were randomly assigned (1:1) to receive either a combination of oral clarithromycin 500 mg, metronidazole 400 mg, and lansoprazole 30 mg (active eradication), or oral placebo (control), twice daily for 1 week. Participants, their general practitioners and health-care providers, and the research nurses, trial team, adjudication committee, and analysis team were all masked to group allocation throughout the trial. Follow-up was by scrutiny of electronic data in primary and secondary care. The primary outcome was time to hospitalisation or death due to definite or probable peptic ulcer bleeding, and was analysed by Cox proportional hazards methods in the intention-to-treat population. This trial is registered with EudraCT, 2011-003425-96.

Findings

Between Sept 14, 2012, and Nov 22, 2017, 30166 patients had breath testing for H pylori, 5367 had a positive result, and 5352 were randomly assigned to receive active eradication (n=2677) or placebo (n=2675) and were followed up for a median of 5·0 years (IQR 3·9–6·4). Analysis of the primary outcome showed a significant departure from proportional hazards assumptions (p=0·0068), requiring analysis over separate time periods. There was a significant reduction in incidence of the primary outcome in the active eradication group in the first 2·5 years of follow-up compared with the control group (six episodes adjudicated as definite or probable peptic ulcer bleeds, rate 0·92 [95% CI 0·41–2·04] per 1000 person-years vs 17 episodes, rate 2·61 [1·62–4·19] per 1000 person-years; hazard ratio [HR] 0·35 [95% CI 0·14–0·89]; p=0·028). This advantage remained significant after adjusting for the competing risk of death (p=0·028) but was lost with longer follow-up (HR 1·31 [95% CI 0·55–3·11] in the period after the first 2·5 years; p=0·54). Reports of adverse events were actively solicited; taste disturbance was the most common event (787 patients).

Interpretation

H pylori eradication protects against aspirin-associated peptic ulcer bleeding, but this might not be sustained in the long term.

DOI: 10.1016/S0140-6736(22)01843-8

Source: https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(22)01843-8/fulltext