Girard P, Sourdet S, Cantet C, et al. Acetaminophen Safety: Risk of Mortality and Cardiovascular Events in Nursing Home Residents, a Prospective Study. J Am Geriatr Soc. 2019 Mar 26. doi: 10.1111/jgs.15861. (Original study)

BACKGROUND: Acetaminophen is the most widely used analgesic today. A recent systematic review found increased adverse events and mortality at therapeutic dosage. Our aim was to challenge these results in a large sample of older adults living in nursing homes (NHs).

DESIGN: Prospective study using data from the Impact of Educational and Professional Supportive Interventions on Nursing Home Quality Indicators project (IQUARE), a multicenter, individually tailored, nonrandomized controlled trial in NHs across southwestern France.

SETTING/PARTICIPANTS: We studied data from 5429 participants living in 175 NHs (average age, 86.1 ± 8.1 years; 73.9% women).

MEASUREMENTS: All prescriptions obtained at baseline were analyzed by a pharmacist for acetaminophen use as stand-alone or associated. Myocardial infarction (MI) and strokes were reported from participants' medical records at 18-month follow-up. Dates of death were obtained. Data collection was done through an online questionnaire at baseline and at 18 months by NH staff. Analyses were realized in our total population and a population matched on propensity score of acetaminophen intake. Six models were run for each outcome.

RESULTS: A total of 2239 participants were taking, on average, 2352 ± 993 mg of acetaminophen daily. Results for mortality were: hazard ratio (HR) = 0.97 (95% confidence interval [CI] = 0.86-1.10). No associations between acetaminophen intake and the risk of mortality or MI were found. In one of our models, acetaminophen intake was associated with a significant increased risk of stroke in diabetic subjects (HR = 3.19; 95% CI = 1.25-8.18; P = .0157).

CONCLUSION: Despite old age, polypharmacy, and polymorbidity, acetaminophen was found safe for most, but not all, of our NH study population. Pain management in NHs is a health priority, and acetaminophen remains a good therapeutic choice as a first-line analgesic. More studies are needed on older diabetic patients.

Discipline Area Score
Physician 6 / 7
Comments from MORE raters

Physician rater

This secondary analysis of the IQUARE study explored the association between baseline acetaminophen use and 18-month mortality & CV event risk in ~ 5000 NH residents. Propensity scores were used to match subjects. Notwithstanding the authors' assurance that the approach would be close to a RCT in terms of research quality, all potential confounders were likely not accounted for in this observational study. No overall increase in mortality, MI or stroke risk was found with acetaminophen use but there was an increased stroke risk in diabetic residents (HR 3.19) not seen in non-diabetics. The authors concluded acetaminophen remained a first-line analgesic for most of this population but use could increase stroke risk in diabetics. They called for more studies in older diabetics. The benefits of therapy were not considered, nor the risks of alternative approaches to pain relief. Caution should be used with all medications but I’m unclear if this report should otherwise alter practice.

Physician rater

The propensity score matched cohort analysis verifies what many providers already assumed: acetaminophen is a relatively safe drug. I’m not sure the study design is strong enough to convince skeptics to change their current prescribing practices. Conversely, I doubt there will be enough interest in conducting an RCT of a medication that has been off-patent for decades. I’m afraid this trial is unlikely to change clinical practice.

Physician rater

This is a noble effort trying to clarify the safety of acetaminophen. Let's face it, there do not seem to be ANY meds we can use for pain without someone objecting. Opioids, NSAIDs, gabapentinoids, tricyclics, SSRIs. I get a note from Pharmacy about all of them. A concern about this paper is that the acetaminophen users and non-users seem significantly different in important ways, which confound the results.

Physician rater

This is a very useful article and shows clinicians that they can prescribe acetaminophen to nursing home residents without much concern about significant adverse effect except some increase in stroke risk (wide 95% CI).
Comments from PAIN+ CPN subscribers

No subscriber has commented on this article yet.