Strategies around a cornerstone treatment for equine gastric ulcers have been called into question by a researcher, who believes a rethink is needed over dietary recommendations during treatment, and the current blanket dosing recommendations for omeprazole.
Equine squamous gastric disease affects the upper part of the stomach, where tissues have limited defence mechanisms against acid. Equine glandular gastric disease affects the lower acid-producing portion of the stomach, where the cells normally have protection mechanisms against lower pH levels. Research suggests that there are different risk factors for gastric ulcers affecting the lower part of the stomach and those affecting the upper portions. Both diseases are common in horses.
University of Queensland Associate Professor Ben Sykes, who has a particular research interest in gastric ulcers in horses, argues in the journal Equine Veterinary Education that current blanket dosing recommendations for omeprazole should be replaced by individually tailored plans which consider each individual horse’s diet and responsiveness to the drug.
Regardless of the cause of disease, suppression of stomach acid is considered the central treatment, and oral omeprazole has been the main treatment for equine gastric ulcer syndrome for nearly 20 years. However, 15–30% of horses with equine squamous gastric disease and 75% of those with equine glandular gastric disease fail to heal within current treatment guidelines.
Turning to equine squamous gastric disease affecting the upper stomach, Sykes says while healing rates from oral omeprazole are 70–85% over a four-week treatment period, scant attention had been paid to the 15–30% of cases that failed to heal completely within this time. “Whether these cases represent the failure to address risk factors such as diet and exercise in clinical studies, or sub-therapeutic responses to oral omeprazole is unclear,” he writes. Recent evidence suggests that if adequate acid suppression is achieved, healing will occur regardless of diet and exercise risk factors. He believes the persistence of these upper lesions after oral omeprazole points to inadequate acid suppression rather than the contribution of other risk factors such as diet, exercise and changes in bacterial populations.
Sykes, turning to ulcers affecting the lower acid-producing part of the stomach – says the way these lesions come about is poorly understood and the risk factors not fully explained. They are believed to result from a breakdown of normal stomach defence mechanisms and the exposure of sensitive tissues to acid. Response to oral omeprazole in these cases is often poor, for reasons that remain unclear.
Sykes suggests four mechanisms likely contribute to the poor healing rate:
- Inadequate acid suppression;
- Inadequate treatment duration;
- Failure to consider where supporting therapy is required;
- Whether acid suppression is the main mechanism needed to heal the ulcers.
He says an understanding of the factors that affect omeprazole’s performance is important in tailoring treatment plans for affected individuals. Sykes says several factors have been highlighted recently that may affect how well oral omeprazole works.
Until recently, he says, the role of diet in the performance of omeprazole has been understated and the potential for feeding recommendations to affect it largely ignored.
Current recommendations include providing plenty of dietary roughage, but this does not distinguish between the therapeutic and preventative stages of managing ulcers.
“This is an error in clinical reasoning,” he suggests, “and inconsistent with current evidence regarding the significant impact that feeding has on omeprazole absorption and efficacy.”
Having feed available at the horse’s desire (ad libitum), when compared with horses that have had feed withheld overnight, reduced the bioavailability of buffered formulations of omeprazole by about 50–66%, research has shown.
Further, acid suppression in horses receiving unlimited hay is less than horses receiving a high grain/low fibre diet with an overnight fast, with omeprazole given two hours before the morning feed.
For horses with ad libitum hay, currently recommended doses of omeprazole are likely to be ineffective in some animals, he says.
He suggests recommendations be updated to include that, where possible, omeprazole should be given after an overnight fast. “This small management change has significant potential to increase the efficacy of oral omeprazole in many patients.
“Once omeprazole treatment is completed, the current recommendation for ad libitum roughage as part of prevention management is appropriate as long as concurrent oral omeprazole therapy is not required for prevention.
“It is likely,” he continues, “that the timing of feeding is important to the drug’s efficacy.” He therefore recommends withholding feed overnight, administration of omeprazole first thing in the morning, followed by the feeding of a large, roughage-based meal 60–90 minutes later, then any required grain/supplement feeding.
He believes that individual responsiveness is a more important factor in tailoring treatment. Dosing, he argues, should be considered for each horse with the goal of finding the minimally effective dose for each animal under its specific dietary conditions.
In conclusion, he argues that greater attention should be given to the impact of feeding on drug absorption and the role of individual dose responsiveness in horses.
Sykes, B. W. (2018), Courses for horses: Rethinking the use of proton pump inhibitors in the treatment of equine gastric ulcer syndrome. Equine Vet Educ. doi:10.1111/eve.12894
The abstract can be read here.