New French research has revealed that low-dose aspirin in giant cell arteritis reduces the risk of major cardiovascular events but is also associated with an increased risk of bleeds.
Using aspirin in patients with giant cell arteritis is a real balancing act, according to new research.
The inflammatory processes associated with giant cell arteritis have also been linked to cardiovascular disease. European guidelines have gone back and forth on whether low-dose aspirin should be used for primary CVD preventative at the time of diagnosis.
A team of French researchers have tried to better understand the benefits and risks to help inform clinical practice by using a target trial emulation approach and observational data.
Their findings, published in JAMA Network Open, suggest low-dose aspirin at the time of diagnosis simultaneously reduces the risk of cardiovascular events while increasing the risk of haemorrhage.
The researchers used retrospective health insurance claim data, hospital discharge data and death certificate date from the French National Health Data System. Patients were included in the study if they had been hospitalised for GCA between 2010 and 2022, were ≥50 years old and had no history of cardiovascular events.
Patients who had received antiplatelet or anticoagulation therapy in the three months prior to GCA diagnosis were excluded.
Pharmacy dispensing data were also examined to determine whether or not patients had initiated low-dose (75 to 300mg) aspirin at discharge from hospital. Patients were followed up for a minimum of 12 months after their first admission for GCA.
The final sample included 14,528 patients with a median age of 74 years. Seventy-two per cent of patients were female, and 36% initiated low-dose aspirin within 14 days of hospital discharge.
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After adjusting for factors such as age at GCA diagnosis, sex, socioeconomic status, CVD risk factors, comorbidities and other GCA-related variables, GCA patients who received low-dose aspirin were 14% less likely to experience a major adverse cardiovascular event (acute myocardial infarction, stroke or death from any cause) after one year compared to patients who did not receive aspirin (relative risk 0.86, 95% confidence interval 0.75-0.96).
However, patients in the aspirin group were also 29% more likely to experience a major haemorrhage in the first 12 months compared to patients who did not receive aspirin (RR 1.29, 1.05-1.53). This association was driven by an increased likelihood of patients experiencing a digestive (RR 1.44, 1.07-1.78) or other kind of haemorrhage (1.80, 1.21-2.33) but not an intracranial haemorrhage (1.22, 0.70-1.70).
The lower likelihood of MACE in patients taking aspirin persisted after three years (RR 0.88, 0.80-0.95). Treated patients were less likely to experience a myocardial infarction (0.72, 0.56-0.88) or stroke (0.82, 0.65-0.97) compared to patients who did not receive aspirin but there was no difference in all-cause mortality (0.93, 0.83-1.03).
There was no association between taking aspirin and the likelihood of haemorrhage at the three-year time point.
“Overall, the net clinical benefits considering both ischaemic and bleeding outcomes were neutral at one year (RR 1.02, 0.90-1.13) and at three years (0.93, 0.86-1.00), mostly because bleeding risk with low-dose aspirin attenuated over time and was no longer statistically different between groups at three years,” wrote Dr Guillaume Marquis-Gravel (an interventional cardiologist and clinical scientist at the Montreal Heart Institute) and Dr Jean-Paul Makszoum (a clinician scientist at the Hôpital du Sacré-Coeur de Montréal) in an invited commentary accompanying the new research.
“These findings were generally consistent in a prespecified observational analog of per-protocol analysis and in a variety of sensitivity analyses, adding robustness and depth to the findings.”
Sex-specific associations were also observed. Men in the low-dose aspirin group were 75% more likely to experience a major haemorrhage than men who did not receive aspirin but were not less likely to experience a MACE in the first 12 months (1.03, 0.80-1.25).
Conversely, women were less likely to experience a MACE (0.79, 0.65-0.92) and did not have an increased risk of haemorrhage (1.00, 0.77-1.22).
“Taken together, our findings may reflect population-specific mechanisms, such as underdiagnosed CVD in women before GCA diagnosis, related to atypical symptoms and distinct plaque characteristics, potentially contributing to the early associations between low-dose aspirin use and reduced MACE risk in women,” the researchers concluded.
Dr Maquis-Gravel and Dr Mahkzoum concurred that moving away from a one-size-fits-all approach for the use of aspirin in patients with GCA would be beneficial.
“A selective strategy mirroring contemporary cardiovascular prevention principles may be reasonable, while recognising that the absence of RCT data in GCA justifies a more cautious approach. For now, in clinical practice, patients’ preferences and values regarding ischaemic and bleeding risks need to be taken into account in a shared-decision making process,” they wrote.
