GI side effects of NSAIDs in dogs

Imagine this scenario: you are treating a canine patient with arthritic pain and intend to prescribe non-steroidal anti-inflammatory drugs (NSAIDs). The patient has no con­traindications for prescribing an NSAID and has not been prescribed NSAIDs before. However, the owner is concerned about potential gastrointestinal (GI) side effects, so you want to investigate the evidence behind whether carprofen or meloxicam is preferential for reducing GI side effects.

The evidence

Three prospective randomised controlled studies were iden­tified, two of which studied the effects of carprofen or meloxi­cam administration on gastrointestinal adverse reactions. Both used endoscopic-measured gastric mucosal lesion scor­ing following oral NSAID administration, with one study addi­tionally measuring an outcome of faecal occult blood. The other study measured the effects of carprofen or meloxicam administration on gastric permeability and mucosal absorp­tive capacity through sugar solution absorption.

In one study by Luna et al. (2007), the subjects (six in each experimental group) were treated with either meloxi­cam or carprofen, with gastric mucosal lesion grading and occult faecal blood tests studied after 90 days of treatment. Gastric lesions were graded by a blinded veterinarian; however, no statistical analysis was performed. It was reported that carprofen had a lower gastric mucosal lesion scoring than meloxicam and that the proportion of positive occult faecal blood tests was lower in the carprofen treated group. However, the study provides weak evidence; limita­tions include small sample sizes and a large dropout rate, and the NSAID doses did not follow the licensed dosage for common preparations.

A further study (Craven et al., 2007) investigated two groups of ten patients who were administered either meloxicam or carprofen once daily. A permeability test to measure sugar solution absorption was administered to the subjects before NSAID therapy on days one, three and eight. Sucrose is digested as it enters the small intestine, so permeation and urinary excretion is considered to reflect gastric permeability. The results showed no statistically significant difference in gastric permeability in canines receiving standard doses of carprofen or meloxicam in the acute phase. Limitations include small group sizes, and limited evidence showing that sugar absorption deficiency correlates to GI side effects (current evidence is based on human medicine only).

The final study (Forsyth et al., 1998) contained four treat­ment groups: carprofen, meloxicam, ketoprofen and an oral placebo – gelatine. Each subject received a gastric endos­copy for assessment of grossly visible lesions before the start of the study. Repeat endoscopic examination and grad­ing was performed after seven days and 28 days of NSAID administration. No significant difference between gastric lesion scores was identified between the NSAID groups and the placebo group. Limitations include small group sizes, some subjects had gastric lesions before treatment and the method of randomisation was not stated.

Conclusion

There is insufficient evidence supporting the preferential administration of carprofen or meloxicam to reduce GI side effects in canines. Two studies reported no statistically significant difference in gastric mucosal lesion scoring and gastric permeability (Forsyth et al., 1998; Craven et al., 2007) between carprofen and meloxicam treatment groups. The third study reported that carprofen had lower gastric mucosal lesion scoring than meloxicam, but was not statis­tically backed (Luna et al., 2007).

The clinical relevance of the studies is debatable, as the subjects were excluded if they developed commonly out­wardly detectable GI signs. While two of the studies meas­ured objective outcomes, these were not correlated to an increased frequency of the common GI side effects reported in practice following NSAID treatment (Monteiro-Steagall et al., 2013). Gastric endoscopy and sugar absorption are also not commonly used techniques to assess GI side effects in first opinion practice.

Further limitations of all critically appraised studies include that the dose and duration of NSAIDs varied between the studies, and that power calculations for the populations used and confidence intervals for outcome measures were not calculated, which increases the risk of type one and type two errors. Additionally, in human medi­cine there is marked variability in an individual’s reaction to NSAIDs (Bruno et al., 2014), which was not accounted for.

NSAIDs are a widely used analgesic in veterinary medi­cine, and while there is high-strength evidence document­ing the adverse effects of these drugs (Monteiro-Steagall et al., 2013), there is a lack of comparative research to guide rational clinical decision making between products. Further research is necessary, and crossover studies would be an appropriate study design to assess the side effects of NSAIDs while reducing the impact of any individ­ual drug reactions.

The full Knowledge Summary can be read in RCVS Knowledge’s open access journal Veterinary Evidence.