Patients at risk for gastric ulcers from long-term, low-dose aspirin regimens who received a novel aspirin therapy had significantly less ulceration, compared with those who received standard low-dose aspirin in a randomized, single-blind trial. The findings were published in the February issue of the American Journal of Gastroenterology.
Preclinical studies have shown that the noncovalent association of aspirin and phosphatidylcholine helps aspirin travel across the gastrointestinal mucosa with less risk for bleeding, said Dr. Byron Cryer of the University of Texas Southwestern Medical Center and Veterans Affairs North Texas Health Care System, Dallas, and his colleagues. This is important, the authors wrote, because "45% of patients with cardiovascular risk factors are not treated with antiplatelet agents because their risks of gastrointestinal (GI) bleeding outweigh [the] vascular benefit."
After 7 days of daily treatment, only 22% of patients randomized to an aspirin-phosphatidylcholine complex known as PL2200 developed six or more gastrointestinal erosions or an ulcer, compared with 42% of those randomized to immediate-release low-dose aspirin alone, a significant difference (P = .0027). Endoscopy was used to evaluate the upper-GI mucosa.
In addition, significantly fewer patients developed gastroduodenal ulcers in the PL2200 group, compared with the low-dose aspirin group (5% vs. 18%, respectively, P = .0069); this amounted to a 71% lower incidence of ulcers in the PL2200 group. The intent-to-treat population included 99 patients in the PL2200 group and 102 patients in the low-dose aspirin group. The patients were healthy and ranged in age from 50 to 74 years; they were considered at risk for GI injury because of their age (Am. J. Gastroenterol. 2011 [doi:10.1038/ajg.2010.436]).
For 7 days, the low-dose aspirin group received 325 mg of aspirin orally once a day, and the PL2200 patients received one PL2200 capsule that contained 325 mg of aspirin once a day. A total of 7 patients in the PL2200 group and 11 in the low-dose aspirin group were excluded because of baseline GI erosion, and 1 patient in each group was excluded for taking a prohibited medication during the study period. These exclusions left a per-protocol population of 91 subjects in the PL2200 group and 90 in the low-dose aspirin group. The percentages of patients that developed ulcers in the per-protocol analysis were similar to those in the intent-to-treat population.
No treatment-related discontinuations or serious adverse events were reported in either group.
"The study suggests that local effects that disrupt the gastric barrier to acid are an important component of aspirin-induced gastropathy," the researchers wrote. The relative contributions of local and systemic mechanisms that induce GI injury are not well understood, they added.
The study was limited by the short-term follow-up, and larger, longer-term studies are needed. However, the findings suggest that PL2200 is associated with significantly better GI safety than low-dose aspirin. Consequently, PL2200 might improve compliance in at risk patients who are likely to discontinue aspirin due to GI side effects, the researchers added.
All study authors, endoscopists, and investigators were blinded until database lock.
The study was funded by the National Institute of Diabetes and Digestive and Kidney Diseases and by PLx Pharma Inc., which is developing PL2200. Dr. Cryer has served as a consultant for multiple pharmaceutical companies including PLx Pharma, AstraZeneca Pharmaceuticals, and Cogentus Pharmaceuticals, and has served on advisory and review committees for Pfizer. Several study coauthors have received research support from or are employed by PLx Pharma or disclosed relationships with other pharmaceutical companies.