A large cohort study of UK adults aged 65 and older found acetaminophen use was associated with increased risks of serious gastrointestinal, cardiovascular, and renal adverse events compared to non-use, according to research published in Arthritis Care & Research.

The study of 180,483 acetaminophen users and 402,478 non-users found that acetaminophen exposure was linked to higher rates of peptic ulcer bleeding (adjusted hazard ratio [aHR] 1.24; 95% CI 1.16-1.34), uncomplicated peptic ulcers (aHR 1.20; 95% CI 1.10-1.31), and lower gastrointestinal bleeding (aHR 1.36; 95% CI 1.29-1.46).

Cardiovascular and renal complications occurred more frequently among acetaminophen users, with increased risks of heart failure (aHR 1.09; 95% CI 1.06-1.13), hypertension (aHR 1.07; 95% CI 1.04-1.11), and chronic kidney disease (aHR 1.19; 95% CI 1.13-1.24).

At the time of the study's publication, the UK's National Institute for Health and Care Excellence (NICE) had revised its guidelines to no longer recommend acetaminophen as a routine treatment for osteoarthritis.

The researchers analyzed data from the Clinical Practice Research Datalink between 1998 and 2018, defining acetaminophen exposure as at least 2 prescriptions within 6 months. They employed propensity score matching and inverse probability treatment weighting to account for confounding factors.

A dose-response relationship emerged for several adverse events, with risks increasing alongside the number of acetaminophen prescriptions. This pattern appeared for peptic ulcer bleeding, uncomplicated ulcers, and chronic renal failure.

In a subgroup analysis of 115,387 participants with osteoarthritis, acetaminophen use was associated with elevated risks of lower GI bleeding (aHR 1.20; 95% CI 1.09-1.33), hypertension (aHR 1.06; 95% CI 1.00-1.13), and chronic renal failure (aHR 1.15; 95% CI 1.09-1.22).

The researchers noted that while previous randomized controlled trials had not found major adverse effects with acetaminophen use, such trials were primarily designed to assess efficacy rather than safety and typically involved healthier, younger participants over shorter durations.

Study limitations included the inability to capture over-the-counter acetaminophen use. The researchers partially addressed this by focusing on adults aged 65 and older who received free prescriptions in the UK. The team noted that propensity score matching could only control for known confounding factors.

The research team indicated future studies should examine acetaminophen prescription as a time-varying exposure to further validate these findings.

Conflict of interest disclosures can be found in the study.