Researchers aimed to measure the incidence of GI bleeding, heart failure, myocardial infarction, hypertension and chronic renal failure, and analyze the dose-response relationship between acetaminophen prescriptions and specific adverse events.
Study Details
The study included participants aged 65 and older because they are eligible in the U.K. to receive free prescriptions from their general practitioner. Participants who received at least two acetaminophen prescriptions within two months, but not in combination with other analgesics, such as codeine, were defined by the researchers as exposed to acetaminophen. This helped exclude occasional use of acetaminophen for other acute conditions, such as headache or the flu.
The control group was made up of participants also aged 65 and older with fewer than two acetaminophen prescriptions within six months during the study period. They were individually matched to acetaminophen users by year of birth, sex, general practice, comorbidity and other confounding factors.
The study ultimately included 180,483 acetaminophen users and 402,478 non-users. The mean participant age was 74.8 years old; more women were participants than men.
Researchers found an increased incidence of peptic ulcer bleeding, uncomplicated ulcers, lower GI bleeding, heart failure, hypertension and chronic renal failure in participants exposed to acetaminophen vs. those who were not. The development of peptic ulcer bleeding, uncomplicated ulcers and chronic renal failure rose with the number of acetaminophen prescriptions.
Among the sub-group of patients with OA (i.e., 24,406 acetaminophen exposed and 24,406 unexposed), acetaminophen exposure was associated with a higher incidence of lower GI bleeding, hypertension and chronic renal failure.
Implications & Context
The study fundings match what other observational studies have reported regarding a link between acetaminophen use and GI complications, as well as hypertension, according to the researchers, citing studies from Rahme et al., Chan et al., Zeng et al. and others.6-8
One study they cited found acetaminophen “exerts an inhibitory effect on peripheral cyclooxygenase [COX] enzymes,” which meant it could be a potential mechanism for GI bleeding when it occurs.9
The researchers noted that most RCTs with acetaminophen have not found any major adverse effects. “This is because the RCTs were primarily designed for efficacy rather than adverse events, solely reported short-term effects, were less powered and recruited healthier and younger participants,” they wrote.
It’s possible that long-term use of acetaminophen could inhibit prostacyclin synthesis, which would lead to GI lesions and bleeding. Medical professionals may want to proceed with caution when considering long-term acetaminophen use for patients.
