Sibilia Jean, Ravaud Philippe, Marck Géraldine
Service de rhumatologie, CHU de Strasbourg, Hôpital de Hautepierre, Strasbourg.
Presse Med. 2003 Nov 22;32(37 Pt 2):S17-28.
The gastro-intestinal (GI) toxicity associated with high dose aspirin has been fully demonstrated, but remains poorly elucidated at low doses i.e., less than 500 mg/day. Such toxicity is relatively difficult to study because lesional and/or bleeding GI complications are not always well described in studies. The objective of this review is to compile a documented inventory of GI complications induced by low-dose aspirin.
This review is based on a detailed review of randomized studies, case-control and cohort studies which aim to study the GI toxicity of low-dose aspirin. These studies have been selected based on specific criteria from works published from 1983 to 2003 (PubMed).
In 8 randomized, placebo-controlled or group-controlled studies, erosions, in particular gastric erosions, are more frequent in the elderly than in younger subjects. On the other hand, the prevalence of gastric and duodenal ulcers does not appear to be significantly increased except in specific cases. The most significant complications are GI bleeding described only in 3% of cases. Among randomized studies which have evaluated the cardiovascular and neurological usefulness of low-dose aspirin, 16 have evaluated GI safety and tolerability as a secondary end-point. These studies demonstrated a non-significant increase in esophageal, gastric and duodenal ulcers during treatment with low-dose aspirin (Odds Ratio = 1.22, P = 0.08), but a significant increase in bleeding ulcers (Odds Ratio = 1.77, P = 0.04). These complications seem to occur in rare cases (less than 3% of patients) and often seem minor. Nevertheless, ulcers have been less studied than bleeding because few endoscopic analyses have been performed in these studies. The gastro-duodenal bleeding related to erosions or ulcers are significantly more frequent with Odds Ratios between 1.3 and 3.3 (P < 0.05). There are 8 case-controlled studies and 1 cohort follow-up study which confirm the increased GI risk with low-dose aspirin. GI bleeding adverse effects related mainly to gastro-duodenal ulcers are more frequent in case of the regular use of aspirin.
The GI risk exists, starting with the lowest doses and appears to be dose-dependent. The lesional complications consist mainly of erosive lesions, most often gastric, and rarely true ulcers. Cases of bleeding appear more frequent, but generally are minor. This risk should be taken into account by the prescribing physician and the patient should be informed when treatment with low-dose aspirin is initiated.
高剂量阿司匹林相关的胃肠道（GI）毒性已得到充分证实，但低剂量（即每天小于500毫克）时仍未完全阐明。此类毒性相对难以研究，因为在研究中病变性和/或出血性胃肠道并发症并不总是得到充分描述。本综述的目的是汇编一份关于低剂量阿司匹林所致胃肠道并发症的文献目录。
本综述基于对旨在研究低剂量阿司匹林胃肠道毒性的随机研究、病例对照研究和队列研究的详细回顾。这些研究是根据1983年至2003年发表的文献（PubMed）中的特定标准挑选出来的。
在8项随机、安慰剂对照或组对照研究中，糜烂，尤其是胃糜烂，在老年人中比在年轻人中更常见。另一方面，除特定情况外，胃溃疡和十二指肠溃疡的患病率似乎没有显著增加。最显著的并发症是胃肠道出血，仅在3%的病例中出现。在评估低剂量阿司匹林心血管和神经学效用的随机研究中，16项将胃肠道安全性和耐受性作为次要终点进行了评估。这些研究表明，低剂量阿司匹林治疗期间食管、胃和十二指肠溃疡无显著增加（优势比=1.22，P=0.08），但出血性溃疡显著增加（优势比=1.77，P=0.04）。这些并发症似乎发生在少数病例中（不到3%的患者），且通常似乎较轻。然而，由于这些研究中很少进行内镜分析，溃疡的研究比出血少。与糜烂或溃疡相关的胃十二指肠出血明显更频繁，优势比在1.3至3.3之间（P<0.05）。有8项病例对照研究和1项队列随访研究证实了低剂量阿司匹林会增加胃肠道风险。在经常使用阿司匹林的情况下，主要与胃十二指肠溃疡相关的胃肠道出血不良反应更常见。
胃肠道风险从最低剂量开始就存在，且似乎呈剂量依赖性。病变性并发症主要由糜烂性病变组成，最常见的是胃糜烂，很少有真正的溃疡。出血病例似乎更常见，但一般较轻。开处方的医生应考虑到这种风险，并且在开始低剂量阿司匹林治疗时应告知患者。
