Concurrent cholinesterase inhibitors, NSAIDs linked to peptic ulcer risk

Risk of peptic ulcers increased ninefold when patients ages 65 years and older took cholinesterase inhibitors and NSAIDs concurrently, a Swedish study found, leading the authors to suggest that the combination be considered potentially inappropriate for older patients.

Concomitant use of cholinesterase inhibitors (ChEIs) and NSAIDs poses higher risk of peptic ulcers among adults ages 65 years and older compared with NSAID use alone, a new study found.

Researchers assessed outcomes of adults ages 65 years and older who had a new prescription for ChEIs and NSAIDs and compared each patient's risks in four different periods: use of ChEIs alone, use of NSAIDs alone, the combination of ChEIs and NSAIDs, and use of neither drug class. The register-based self-controlled case series was carried out in Sweden from 2007 to 2020. Findings were published by the Journal of the American Geriatrics Society on Oct. 31.

A total of 70,060 patients started both medications. Of these, 1,500 developed a peptic ulcer. Patients had a median age of 80 years when they had a peptic ulcer, and 58% of these patients were female. The risk of peptic ulcer was substantially higher in patients coprescribed both medications (incidence rate ratio [IRR], 9.0; 95% CI, 6.8 to 11.8) compared with nontreatment periods. Ulcer risk was elevated with NSAIDs alone to a lesser extent (IRR, 5.2; 95% CI, 4.4 to 6.0). ChEIs alone were not associated with peptic ulcers (IRR, 1.0; 95% CI, 0.9 to 1.2).

Most patients with ulcers (68%) were diagnosed in an inpatient setting. Forty-four percent of patients with ulcers also had hypertension, and one quarter had dementia. Being female or being age 80 years and older was also associated with increased ulcer risks (IRRs, 10.4 [95% CI, 7.4 to 14.8] and 12.6 [95% CI, 8.5 to 18.5], respectively).

“These findings confirm that increased age is a risk factor for gastrointestinal toxicity, and contributes to filling the knowledge gap in sex-related differences in drug safety research,” the study authors wrote. They suggested that physicians consider deprescribing NSAIDs among patients initiating ChEI treatment and that chronic ChEI users refrain from starting NSAIDs. “We suggest including the ChEIs and NSAIDs drug–drug interaction in potentially inappropriate medication use criteria to raise awareness among prescribers,” they added.

Among other limitations, the study could not differentiate between bleeding and nonbleeding ulcers. Data also did not capture medication adherence. “Our results underscore the importance of carefully considering the risk of peptic ulcers when co-prescribing NSAIDs and ChEIs to adults aged 65 years and older. Further research is warranted to validate the effect size estimates using an even larger population,” the researchers concluded.