From Peptic Ulcer Disease to NSAID Gastropathy

Abstract

Nonsteroidal anti-inflammatory drug (NSAID)-induced gastropathy is an important clinical entity, most commonly encountered in elderly female patients. The expanding use of NSAIDs in the elderly population has led to an increased incidence of NSAID-induced gastropathy. The risk of gastric bleeding in these patients is 7-fold higher than in the younger population. Long term NSAID therapy in the elderly is apparently associated with failure of normal gastric mucosal adaptation. Silent unidentified gastric lesions are likely to be common with long term NSAID therapy, as symptomatology does not parallel pathological progression. This gastropathy, in contrast to peptic ulcer disease, is responsive to prostaglandins and other cytoprotective agents. A new generation of prostaglandin-sparing NSAIDs (e.g. nabumetone), in addition to the older nonacetylated salicylates, may represent less gastrotoxic alternatives. Therefore, these agents may substantially reduce the risk of NSAID-induced gastropathy. The debate continues as to whether to use NSAIDs, and under which circumstances. More importantly, the cost-benefit implications and justification for concomitant therapy with gastroprotective agents cloud the picture. Currently, there is a definite consensus that NSAIDs should not be casually used on a chronic basis, especially in patients at risk for serious gastropathy complications. In all cases, where possible, gastric prostaglandin-sparing NSAIDs or nonacetylated salicylates should be used in lowest effective dosages. In special circumstances, gastroprotective co-therapy can be considered. NSAID therapy probably should not be used or continued in elderly patients with a history of bleeding ulcers or recent major gastric ulcer activity.

A comparison of the upper gastrointestinal mucosal effects of valdecoxib, naproxen and placebo in healthy elderly subjects

“…These findings are especially noteworthy since the study population was elderly and considered to be at high risk for NSAID-related gastropathy. [30][31][32] These results are also consistent with endoscopy trials of identical duration in healthy elderly subjects (65-75 years old), which evaluated the gastrointestinal safety of parecoxib sodium, the parenterally administered prodrug of valdecoxib, and highlighted the elevated risk of NSAIDrelated gastrointestinal ulceration in this patient subset. 24,25 It is conceivable that the safety advantage of treatment with a supratherapeutic dosage of valdecoxib over naproxen in these 7-day endoscopic studies may just reflect the topical effects of this acidic, nonspecific NSAID and therefore only be short-term and unrelated to a COX-1 sparing effect.…”

Improving drug use in rheumatic disorders

“…It is estimated that NSAIDs are responsible for 1500 hospitalizations due to severe upper gastrointestinal adverse effects each year in Australia, with a resultant mortality rate of about 10% (i.e. NSAIDs contribute to 1 O S 2 O O deaths each year due to upper gastrointestinal haemorrhage and perforation) (1)(2)(3)(4)(5)(6)(7). The prevalence of peptic ulcers in patients who are taking NSAIDs is approximately 15-20%, with most ulcers occurring in the stomach (2,4).…”

Patología digestiva alta en pacientes de edad avanzada con anemia ferropénica: comparación entre usuarios y no usuarios de anti-inflamatorios no esteroideos

“…Por otro lado, y de modo más probable, los AINEs pueden ejercer un efecto de selección ya que son capaces de inducir anemia ferropénica por sus propios mecanismos. Es bien conocida la asociación entre el uso de AINEs y la presencia de lesiones gastrointestinales sangrantes (25,26,28), sobre todo en pacientes ancianos (24). Sin embargo, es de destacar que muchos (más de un tercio) de los usuarios de AINEs con anemia ferropénica de nuestra serie no presentaban lesiones en la endoscopia digestiva alta, de modo similar a lo publicado previamente (12,13).…”

“…Es bien sabido que los AINEs pueden favorecer el sangrado gastrointestinal. Además, en el anciano las complicaciones del uso de AINEs son más frecuentes (25)(26)(27)(28). Por todo ello, el presente estudio fue encaminado a evaluar si una historia de uso habitual de AINEs se asociaba con determinadas patologías en el tramo digestivo alto de pacientes ancianos con anemia ferropénica.…”