Gastrointestinal injury associated with NSAID use: a case study and review of risk factors and preventative strategies

Figures & data

Figure 1 Endoscopic image of a 1×1 cm hemorrhagic gastric ulcer in the antrum with a visible vessel revealed by endoscopy.

Note: Endoscopy is from a 53-year-old woman presenting to the emergency department following two bouts of hematemesis and a melenic stool.

Figure 2 Incidence of UGI complications with increasing duration of NSAIDs in the MUCOSA and VIGOR trials.

Notes: The MUCOSA trial (A) evaluated the effects of misoprostol- co-administration with a variety of nonselective NSAIDs (eg, naproxen, ibuprofen, diclofenac, and others) on gastrointestinal complication rates. Reproduced from Silverstein FE, Graham DY, Senior JR, et al. Misoprostol reduces serious gastrointestinal complications in patients with rheumatoid arthritis receiving nonsteroidal anti-inflammatory drugs. A randomized, double-blind, placebo-controlled trial. Ann Intern Med. 1995;123(4): 241–249.¹⁴ The VIGOR trial (B) compared the gastrointestinal effects of naproxen and rofecoxib overtime. Reproduced from N Engl J Med, Bombardier C, Laine L, Reicin A, et al; VIGOR Study Group, Comparison of upper gastrointestinal toxicity of rofecoxib and naproxen in patients with rheumatoid arthritis. VIGOR Study Group. 2000;343(21):1520–1528. Copyright ©2000 Massachusetts Medical Society. Reprinted with permission from Massachusetts Medical Society.¹⁵ In both trials, the incidence of upper gastrointestinal complications with NSAIDs was began early, linear, constant, and was present for the duration of NSAID exposure.
Abbreviations: MUCOSA, Misoprostol Ulcer Complication Outcomes Safety Assessment; NSAID, nonsteroidal anti-inflammatory drug; UGI, upper gastrointestinal; VIGOR, Vioxx Gastrointestinal Outcomes Research.

Table 1 Characteristics of patients with an elevated risk for NSAID-associated gastrointestinal complications

Characteristics

• Age >60 years^Citation53,Citation54

• Helicobacter pylori infection^Citation57

• Receiving hemodialysis^Citation52

• High-dose or multiple NSAID use^Citation55

• History of upper gastrointestinal injury^Citation14,Citation51

• Anticoagulant use^Citation58,Citation59

• Oral corticosteroid use; prednisone^Citation55,Citation60

• Selective serotonin reuptake inhibitor use^Citation61,Citation62,Citation64

Abbreviation: NSAID, nonsteroidal anti-inflammatory drug.

Table 2 Gastroprotective strategies to prevent gastrointestinal complications associated with NSAID use

Preventative strategy	Gastroprotection strategy	Disadvantages
Proton-pump inhibitors^Citation70^–^Citation73	Reduce secretion of gastric acid	Associated with increased risk of pneumonia, hypomagnesemia, Clostridium difficile-associated diarrhea, and spine and hip fractures
Misoprostol^Citation74,Citation75	Synthetic prostaglandin that counteracts prostaglandin inhibition by NSAIDs	Gastrointestinal discomfort, nausea, and diarrhea; fetal loss
Histamine-2 receptor agonists^a,70,76	Reduce secretion of gastric acids	Increased risk of pneumonia
COX-2 inhibitors^Citation77	Selective for COX-2 receptor, which circumvents the inhibition of gastroprotective prostaglandins by COX-1	Cardiovascular complications similar to those associated with other NSAIDs
Topical formulations^Citation78	Lowers systemic drug exposure to potentially reduce risk	Impractical for systemic pain and may be ineffective for long-term pain relief
Lower-dose oral formulations^Citation79^–^Citation81	Lowers systemic drug exposure to reduce risk	Limited efficacy and safety data

Note:

a Only effective as a protective agent at 300 mg twice daily for ranitidine, ≥40 mg twice daily for nizatidine, and 80 mg total daily dose for famotidine.

Abbreviations: COX, cyclooxygenase; NSAID, nonsteroidal anti-inflammatory drug.

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