Inaccurate aspirin allergy labels increase odds for poor stroke outcomes
Key takeaways:
- Most NSAID allergy labels are inaccurate.
- Aspirin is first-line treatment for patients with stroke.
- Four of five surviving stroke patients were successfully delabeled.
Patients with stroke and inaccurate NSAID allergy labels had poorer outcomes including major adverse cardiovascular events, peripheral vascular disease and death, according to a study published in Stroke.
Multidisciplinary interventions may improve these outcomes, Philip Li Hei, MD, clinical assistant professor, department of medicine, School of Medicine, LKS Faculty of Medicine of the University of Hong Kong, and colleagues wrote.
“It is well known that the overwhelming majority of penicillin ‘allergy’ labels — the most common implicated drug — are incorrect, and obligatory use of second-line antibiotics are associated with a myriad of adverse clinical outcomes,” Li told Healio.
“Therefore, we postulated that this may also be true for NSAID ‘allergy’ labels, especially among patients at elevated cardiovascular risk,” Li continued.
NSAID allergy labels are more common among patient populations with greater NSAID use, the researchers said, adding that previous studies have found that approximately 80% of these labels are inaccurate.
However, these labels prevent patients with stroke from using NSAIDs and potentially reduce their risk for a repeat event by up to 60%, among other adverse long-term cardiovascular outcomes, the researchers continued.
The combined retrospective, longitudinal and cross-sectional study identified the prevalence of drug allergy labels among the general population (n = 7,337,778) and among patients with a history of stroke (n = 1,003) in the Hospital Authority, which manages approximately 90% of public in-patient services in Hong Kong.
The stroke cohort (median age = 71 years; 40.1% women) included 134 patients (13.4%) with a physician-reported drug allergy, most commonly drugs for the cardiovascular and hematopoietic system (OR = 2.4; 95% CI, 1.74-3.32).
Aspirin was the culprit for 23.9% of the cardiovascular and hematopoietic system drug labels and for 32.4% of the central nervous system drug labels. Diclofenac was the culprit in 31.3% of the eye drug labels and 14.7% of the central nervous system drug labels.
Aspirin and diclofenac were the most common individual drugs with allergy labels, the researchers said. Overall, 18 patients (1.8%) in the stroke cohort had an NSAID allergy label.
After an acute stroke, patients with an NSAID allergy label were less likely to be prescribed aspirin (OR = 0.24; 95% CI, 0.09-0.6) and more likely to be prescribed clopidogrel (OR = 5.33; 95% CI, 2.08-13.7), which is a second-line anti-platelet agent.
During subsequent follow-up, these patients also were less likely to be prescribed aspirin (OR = 0.22; 95% CI, 0.08-0.56) and more likely to be prescribed clopidogrel (OR = 5.2; 95% CI, 2.02-13.34).
Compared with patients who did not have NSAID allergy labels, patients with these labels experienced greater odds for mortality (OR = 7.44; 95% CI, 2.43-22.76) during a median follow-up of 6.7 patient-years.
Additionally, these patients had greater odds for major adverse cardiovascular events (OR = 6.09; 95% CI, 2-18.58) and peripheral vascular disease (OR = 9.35; 95% CI, 1.95-44.86).
Five of the patients in the stroke cohort with an NSAID allergy label (27.7%) were alive when the study was conducted and participated in allergy testing. Two of them had an aspirin allergy label and the other three had nonspecific NSAID allergy labels.
Evaluation determined that these patients were at low risk for a genuine allergy. Drug provocation testing with aspirin yielded negative results for four of these patients. The fifth patient had a mild, delayed-type hypersensitivity reaction.
“NSAID allergy labels were significantly more prevalent among patients with stroke, associated with excessive mortality, peripheral vascular disease and major adverse cardiovascular events,” Li said. “After allergist evaluation, 80% of these NSAID ‘allergy’ labels were found to be incorrect.”
Based on these findings, the researchers said that patients with stroke have a disproportionately higher burden of NSAID allergy labels and are significantly less likely to be prescribed aspirin, which is a first-line treatment, after acute ischemic stroke.
The higher rates of major adverse cardiovascular events, peripheral vascular disease and mortality among these patients are partially due to this reduced likelihood of aspirin, the researchers said.
“Those patients mislabeled with NSAID ‘allergy’ may have tolerated aspirin for stroke prevention and had better clinical outcomes,” Li said. “Given the high rate of mislabeled allergies, multidisciplinary neuro-allergy interventions could have the potential to improve patient outcomes.”
The increased use of clopidogrel, which has been associated with significantly higher mortality when compared with aspirin in large real-world studies, also may have contributed to the higher rates of major adverse cardiovascular evens and mortality, the researchers continued.
The researchers called for future multicenter and dedicated collaborative studies with specialized referral systems that would assess patients with NSAID allergy labels earlier in their treatment.
Also, the researchers encouraged more collaborations between allergists and other specialists as well as systems that would be dedicated to screening and referring patients with cardiovascular disease for drug allergy evaluations.
“Doctors who encounter patients with previously unverified drug ‘allergy’ labels should consider referral for allergist workup for delabeling of incorrect allergies and improve drug choices in the future, before it’s too late,” Li said.
The electronic health records of patients with a history of or a high risk for cardiovascular disease as well as a suspected NSAID allergy could be flagged for further review, with patients at low risk for the allergy prioritized for delabeling, the researchers also recommended.
Physicians and other health care professionals may benefit from systematic and evidence-based education about drug allergies as well, increasing their awareness of the impact of inaccurate drug allergy labels, the researchers added.
“We look forward to prospective and interventional studies, investigating the role of multidisciplinary allergy delabeling strategies to actively delabel incorrect drug allergies before they impose adverse clinical outcomes,” Li said.
Reference:
- HKUMed study finds 80% mislabelled NSAID allergies among stroke patients leads to poorer treatment outcomes and urges evaluation to identify mislabeling. https://www.hku.hk/press/news_detail_28086.html. Published Jan. 22, 2025. Accessed Jan. 28, 2025.
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This is an interesting report. I’d like to make a few points.
First, there were only 18 patients with stroke who were labeled as having an NSAID “allergy.” This limits the power of the statistical analyses for no difference between the groups for many of the measures.
Next, the extent to which those labeled with NSAID “allergy” actually had a possible intolerance at some point (eg, gastric upset, minor bleeding, etc) is not clear.
Third, the study had a retrospective design. There is always a chance of unmeasured confounding, ie, whether the outcomes would have been different if patients labeled as having an NSAID allergy were given aspirin is not known.
Finally, the study cohort was all from Hong Kong. Whether the findings can be generalized to populations with differing demographics and other characteristics remains to be seen.
With these caveats, the importance is that determining whether a patient has an intolerance to a drug, which may be transient, or an allergy is critical and should be clearly documented in the record. If the patient does not have an allergy or an important intolerance, they should be treated with evidence-based therapy as reflected in national guidelines.
The other next step is to replicate the results in a larger, more diverse population of patients.
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