Gargallo Carla J, Sostres Carlos, Lanas Angel
Service of Digestive Diseases, University Hospital Lozano Blesa, c/Domingo Miral s/n, 50009, Zaragoza, Spain.
Curr Treat Options Gastroenterol. 2014 Dec;12(4):398-413. doi: 10.1007/s11938-014-0029-4.
Nonsteroidal anti-inflammatory drug (NSAID) treatment will be necessary as part of our therapeutic armamentarium for many years to come. Therefore, safe prescription is mandatory in order to prevent adverse events. In the last two decades, new strategies and new drugs have been developed to reduce NSAID-associated upper gastrointestinal (GI) adverse events. Although the implementation of guidelines into clinical practice takes time, several studies have shown a recent and profound decrease in hospitalizations due to upper GI complications, which has been linked to widespread use of proton pump inhibitors (PPIs), better NSAID prescription, and decreased prevalence of Helicobacter pylori infection. This is encouraging.Safe NSAID prescription should be straightforward since the most relevant aspects are clinical in nature. Before issuing any prescription, three key questions should be considered:1) Is NSAID treatment necessary for this patient?2) What cardiovascular (CV) and GI risk factors does this patient have?3) What is the most suitable NSAID for this patient?GI and CV risk are easy to estimate, and we know that these risks are not the same for all NSAIDs. Selective cyclooxygenase (COX)-2 inhibitors, like celecoxib at usual doses, carry the lowest GI risk and are the best option in patients with moderate/high GI risk without high CV risk. Gastroprotective therapy (PPI as the drug of choice) should be considered if a non-selective NSAID is prescribed. For those at the highest risk, a combination of PPI plus a coxib is the best option. Also, eradication of H. pylori infection in patients with previous peptic ulcer or in NSAID-naïve users must be considered. Naproxen is the best option in patients with high CV risk and low/moderate GI risk.Patients taking aspirin represent a real challenge for treatment, since interaction with frequently prescribed NSAIDs (e.g. ibuprofen/naproxen) may alter its antiplatelet effect, representing a potential clinical problem. Switching treatment (e.g. taking aspirin before NSAID dosing) may not be an alternative since interaction may persist, especially when taking enteric-coated aspirin. Changing NSAID treatment to diclofenac/celecoxib/etoricoxib may also not be an option in patients with high or previous CV event history. Under these circumstances, careful prescription should be considered at the individual patient level.When dyspepsia develops in an NSAID user, PPI co-therapy plus reduction of the NSAID dose or a change in the type of NSAID are valid alternatives, but clinical experience shows that, for some patients, stopping NSAID therapy may be the only option. After a bleeding episode, most patients can be managed with alternative therapy to NSAIDs, but if needed, a coxib plus a PPI and H. pylori eradication is a safe alternative.
在未来许多年里,非甾体抗炎药(NSAID)治疗仍将是我们治疗手段的一部分。因此,为预防不良事件,安全用药至关重要。在过去二十年中,已开发出新的策略和新药以减少与NSAID相关的上消化道(GI)不良事件。尽管将指南应用于临床实践需要时间,但多项研究表明,因上消化道并发症住院的人数近期已大幅下降,这与质子泵抑制剂(PPI)的广泛使用、更好的NSAID处方以及幽门螺杆菌感染率的降低有关。这令人鼓舞。
安全开具NSAID处方应很简单,因为最相关的方面本质上是临床方面的。在开具任何处方之前,应考虑三个关键问题:
1)该患者是否需要NSAID治疗?
2)该患者有哪些心血管(CV)和GI风险因素?
3)最适合该患者的NSAID是什么?
GI和CV风险很容易评估,而且我们知道所有NSAID的这些风险并不相同。选择性环氧化酶(COX)-2抑制剂,如常用剂量的塞来昔布,GI风险最低,是中度/高度GI风险且无高CV风险患者的最佳选择。如果开具非选择性NSAID,应考虑使用胃保护疗法(首选PPI)。对于风险最高的患者,PPI加coxib联合使用是最佳选择。此外,对于既往有消化性溃疡的患者或未使用过NSAID的患者,必须考虑根除幽门螺杆菌感染。萘普生是高CV风险和低/中度GI风险患者的最佳选择。
服用阿司匹林的患者在治疗方面是一个真正的挑战,因为与常用的NSAID(如布洛芬/萘普生)相互作用可能会改变其抗血小板作用,这是一个潜在的临床问题。更换治疗方法(如在服用NSAID之前服用阿司匹林)可能不是一个选择,因为相互作用可能仍然存在,尤其是服用肠溶阿司匹林时。对于有高CV事件史或既往有CV事件史的患者,将NSAID治疗改为双氯芬酸/塞来昔布/依托考昔也可能不是一个选择。在这种情况下,应在个体患者层面谨慎处方。
当NSAID使用者出现消化不良时,PPI联合治疗加NSAID剂量减少或NSAID类型改变是有效的替代方法,但临床经验表明,对于一些患者,停止NSAID治疗可能是唯一的选择。出血事件发生后,大多数患者可以采用NSAID替代疗法进行治疗,但如有需要,coxib加PPI以及根除幽门螺杆菌是一种安全的替代方法。