Benefit of Aspirin Questionable After Arterial Inflammation Emergencies

The balance between risk and benefit with low-dose aspirin after an episode of giant cell arteritis (GCA) remains murky, according to a French population-based retrospective cohort study.

Patients with a first hospitalization for GCA had a lower 1-year risk of major adverse cardiovascular events (MACE) if they had initiated low-dose aspirin therapy soon after the event (relative risk [RR] 0.86, 95% CI 0.75-0.96), and this advantage persisted at 3 years compared with those who didn’t take low-dose aspirin (RR 0.88, 95% CI 0.80-0.95).

On the other hand, there was a significantly higher risk of major hemorrhage associated with low-dose aspirin use (RR 1.29, 95% CI 1.05-1.53) — though this was no longer observed at 3 years, reported Florence Tubach, MD, PhD, of Hôpital Pitié Salpêtrière in Paris, and colleagues.

“Net clinical benefit was not different across groups at 1 year. There was also no significant difference at 3 years,” the authors wrote in JAMA Network Open.

GCA is a medical emergency predominantly involving the supra-aortic vessels in older people. This rare inflammatory disease traditionally manifests in vision loss and cerebrovascular events. As affected individuals are treated with high-dose corticosteroids and tend to remain at higher cardiovascular risk, aspirin holds some interest as a primary prevention medication.

However, use of aspirin is controversial in this setting, as the overall evidence points to no cardiovascular benefit.

“Accordingly, major guidelines discourage routine aspirin use for primary cardiovascular prevention in individuals with GCA. Whether low-dose aspirin offers net clinical benefits in GCA remains unresolved and clinically important questions suffer from a lack of randomized clinical trial (RCT) data,” wrote Guillaume Marquis-Gravel, MD, MSc, and Jean-Paul Makhzoum, MD, MSc, both of the University of Montreal, in an accompanying editorial.

Moreover, Tubach’s group cited the conflicting evidence on general primary prevention aspirin for older people based on results from the ASPREE, ASCEND, and ARRIVE trials, noting that people with diabetes may be among those who benefit from primary prevention aspirin.

“Some experts have advocated for a more parsimonious and highly selective use of low-dose aspirin in primary prevention,” they pointed out. “These discrepancies directly motivated our study. Patients with chronic inflammatory diseases are at elevated cardiovascular risk, with patients with GCA appearing particularly vulnerable, possibly due to a higher prevalence of baseline risk factors and prolonged corticosteroid exposure.”

In the search for subgroups more likely to benefit, the study authors found a more pronounced association between low-dose aspirin and lower 1-year MACE risk specifically in women and patients with diabetes.

Marquis-Gravel and Makhzoum noted that this study “addresses a true clinical equipoise, reflected by conflicting guideline recommendations and the lack of confirmatory RCTs on the topic.”

“For now, in clinical practice, patients’ preferences and values regarding ischemic and bleeding risks need to be taken into account in a shared decision-making process,” they concluded.

This study relied on a target trial emulation framework using data extracted from the French National Health Data System.

Tubach and colleagues included 14,528 patients ages 50 and older with a first hospitalization for GCA from 2010 to 2022 and no previous cardiovascular events or antiplatelet or anticoagulant use. Median age was 74 years, and 72% were women; 36% were categorized as aspirin initiators after GCA (with a dose of 75-300 mg daily).

Most baseline characteristics were similar between the aspirin and no-aspirin groups before weighting. After weighting, all covariates were well-balanced across groups at the end of a 14-day grace period for treatment initiation.

MACE events included ischemic stroke, myocardial infarction, and all-cause mortality.

The observational study left room for residual confounding, Tubach and team acknowledged. Some patients may have had existing polymyalgia rheumatica as opposed to incident GCA, as suggested by frequent corticosteroid use in the year prior to hospitalization.

“Conducting a definitive RCT in this setting would face important logistical barriers, including rapid treatment initiation after diagnosis, heterogeneity in baseline cardiovascular risk, competing indications for antithrombotic therapy, and the need for large sample sizes in a rare disease to detect modest treatment effects,” Marquis-Gravel and Makhzoum wrote. “In this context, the target trial emulation … is informative, hypothesis generating, and potentially practice influencing.”