Acetaminophen associated with increased risk of ulcers

Commonly used to treat pain or fever, and often recommended as a first-line treatment for osteoarthritis pain— mainly because of its perceived safety compared with other oral analgesics—acetaminophen is not without danger. It increases the incidence of peptic ulcers and gastrointestinal bleeding, among other risks.According to the Quebec Poison Control Centre, it has caused 3,404 poisonings and been implicated in more than 1,900 multiple poisonings, prompting the coroner to issue new recommendations in December 2023 on its optimal use and the risks associated with its consumption, aimed at healthcare professionals. In the U.K., the National Institute for Health and Care Excellence (NICE) stopped recommending acetaminophen (called paracetamol in Europe) as a treatment for osteoarthritis in 2022, due to its non-clinically significant benefit and its potential dangers following reports of gastrointestinal, cardiovascular, hepatic and renal adverse events. A new cohort study1 from the University of Nottingham, England, published in the journal Arthritis Care & Research, confirms the risks of OTC use for gastrointestinal health in the elderly. Prescription usersUsing anonymized data from the Clinical Practice Research Datalink GOLD database, researchers from the examined the medical records of 180,483 patients aged 65 and over who had received prescriptions for oral acetaminophen, and 402,478 patients aged 65 and over who were considered to be non-users of acetaminophen, between 1998 and 2018. In the U.K., people aged 65 and over can be prescribed acetaminophen free of charge by their family doctor. Participants who received at least two prescriptions within six months, and not in combination with other painkillers such as codeine, were defined as exposed to acetaminophen, to exclude occasional use of acetaminophen for acute conditions such as headaches or flu, the study said.The average age of the patients was around 75, and just over 60% were women. Acetaminophen users were also taking opioids, NSAIDs, aspirin, proton pump inhibitors and other types of medication at higher rates; they were also more likely to be overweight or obese, to be current or former smokers and to have co-morbidities.Peptic ulcersThe researchers matched users to non-users in a 1:1 ratio by propensity score, with 79,024 patients in each group. This propensity matching attenuated the differences between the two groups.The authors found that acetaminophen users were 20% to 36% more likely than non-users to develop peptic ulcers (aHR 1.20; 95% CI 1.10, 1.31), bleeding due to ulcers (aHR 1.24; 95% CI 1.16, 1.34), or any type of lower gastrointestinal bleeding (aHR 1.36; 95% CI 1.29, 1.46). The increased incidences of lower gastrointestinal bleeding, hypertension and chronic kidney disease were observed in a subgroup analysis restricted to people with osteoarthritis, in line with those observed in the cohort as a whole.The study also found that acetaminophen use was also associated with increased rates of heart failure (aHR 1.09; 95% CI 1.06, 1.13), chronic kidney disease (aHR 1.19; 95% CI 1.13, 1.24) and hypertension (aHR 1.07; 95% CI 1.04, 1.11)."Despite its apparent safety, paracetamol is associated with a number of serious complications. Given its minimal analgesic efficacy, the use of paracetamol as a first-line oral analgesic for chronic conditions in the elderly should be carefully re-evaluated," the authors concluded. The full study can be read in Arthritis Care & Research.

Acetaminophen associated with increased risk of ulcers

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