Acetaminophen Tied to Stroke Risk in Older Adults With Diabetes

Norra MacReady

April 09, 2019

Use of acetaminophen is associated with an increased risk for stroke among elderly nursing-home residents with diabetes, the authors of a new study report.

In a secondary analysis of data on more than 5000 older adults living in nursing homes in southwestern France, the risks for mortality and cardiovascular outcomes were similar among patients who did and those who did not use acetaminophen, except for those with diabetes. In that subgroup, acetaminophen use was associated with a stroke risk more than three times higher than in nonusers.

Given the effects of diabetes on cardiovascular function, plus the effect of acetaminophen on prostaglandin synthesis and other inflammatory mechanisms, the findings suggest that acetaminophen "could become a triggering factor for strokes," the authors write in an article published online March 26 in Journal of the American Geriatrics Society.

The fact that the patients were elderly also meant that they had had more time to develop cardiovascular risk factors, lead author Philippe Girard, MD, told Medscape Medical News. "Acetaminophen, in such circumstances, might become a triggering factor that unbalances a precarious equilibrium."

Cautious Approach Urged

However, Girard, of the Gérontopôle, Centre Hospitalo-Universitaire de Toulouse, France, also warned that the study findings should be interpreted with caution. "We cannot simply conclude, despite solid statistical analysis, that acetaminophen represents a risk for all diabetic subjects," he said. "Specific studies searching for this particular risk need to be undertaken to confirm or refute these findings."

At least one outside expert concurred with the recommendation for caution. The findings "may be a signal that could lead to other research, but I would not use them to guide clinical practice," Laura C. Hanson, MD, MPH, told Medscape Medical News.

"This was a secondary analysis of data collected for another purpose," said Hanson, who is a professor in the Division of Geriatric Medicine, University of North Carolina School of Medicine, Chapel Hill. "I admire these authors for making use of this data set, but the findings must be placed in the context of all the other data showing that acetaminophen is safe."

Other options do exist for controlling pain in this patient population, Hanson added. She recommended exercise and physical therapy for managing musculoskeletal pain, as well as the use of padding and the careful repositioning of patients who are less ambulatory. Hot and cold packs and topical pain medications also can be "sources of nondangerous, nonharmful pain relief." Neuropathic pain may respond to systemic agents, such as gabapentin (multiple brands), pregabalin (Lyrica, PF Prism CV), or antidepressants.

Girard urged clinicians to aim for treating specific types of pain and to assess the patient's renal and hepatic metabolic capacities before prescribing pain medication.

Study Design and Findings

The study consisted of a secondary analysis of data from the Impact of Educational and Professional Supportive Interventions on Nursing Home Quality Indicators (IQUARE) study, a multicenter, nonrandomized, controlled trial designed to improve quality indicators related to medical problems commonly seen in patients in nursing homes. IQUARE included a 6-month intervention period, followed by an 18-month follow-up. Information about the patients was gathered from questionnaires answered by appropriate staff members at the participating facilities.

The study population included 5429 individuals living in 175 nursing homes (mean age, 86.1 years ±8.1 years). Of those patients, 2239 (41.2%) used acetaminophen, at a mean daily dose of 2352 ± 993 mg. For users of acetaminophen, rates of hypertension and peripheral vascular diseases were higher than for nonusers, but rates of dementia were less.

The primary study outcome was mortality during the follow-up period. During that time, there were 667 deaths among users of acetaminophen, for an incident mortality of 22.34 per 100 person-years (95% confidence interval [CI], 20.64 – 24.03 per 100 person-years). There were 940 deaths among people who did not use acetaminophen, for an incident mortality of 22.16 per 100 person-years (95% CI, 20.75 – 23.58 per 100 person-years; P = .8809).

Stroke and myocardial infarction (MI) during follow-up were the secondary outcomes. After excluding patients who died (n = 1629) or who had a history of MI (n = 243) or stroke (n = 628), there were 77 MIs among 3574 patients (2.15%), including 34 among patients who used acetaminophen and 43 among those who did not (P = .5890). Similarly, 133 strokes occurred in 3189 patients, including 60 among acetaminophen users and 73 among nonusers (P = .2765).

Because the IQUARE study was not randomized, the authors also calculated propensity scores "to account for potentially confounding factors for each outcome," they explain. "This technique allowed us to approach a randomized trial in terms of bias."

The pattern of findings was similar in the propensity-matched population, with no significant differences between acetaminophen users and nonusers in primary and secondary outcomes, with one exception: acetaminophen was associated with an increased risk for stroke among people with diabetes (hazard ratio [HR] = 3.19; 95% CI = 1.25 – 8.18; P = .0157), but not in persons who did not have diabetes (HR = .93; 95% CI = .61 – 1.40; P = .7244).

Acetaminophen is still a safe choice for first-line pain management in frail, elderly patients, the authors conclude. However, as this segment of the population increases, "studies need to focus on the safety of the drugs these frail older adults commonly use to better our practice."

The study was funded by the Agence Regional de Sante Midi-Pyrenees. The study authors and Hanson have disclosed no relevant financial relationships.

J Am Geriatr Soc. Published online March 26, 2019. Full text

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