Does aspirin use improve outcomes in APS patients with arterial thrombosis?

The addition of low-dose aspirin to warfarin appears to increase the risk of major bleeding in patients with antiphospholipid syndrome (APS) but falls short in reducing all-cause mortality, according to a study presented at ASH 2025. Likewise, the rates of ischemic stroke and acute myocardial infarction are also higher among aspirin users.

“This unexpected increase in arterial events may reflect residual confounding by indication, as patients perceived to be at greater thrombotic risk were more likely to receive combination therapy,” said lead author Dr Fayaz Khan, University at Buffalo Roswell Comprehensive Cancer Center, Buffalo, US.

“Despite careful propensity score matching, unmeasured differences in disease severity and clinical decision-making may have contributed to these findings,” he added.

Khan and his team used the TriNetX Network to carry out this retrospective study involving two cohorts: (1) APS patients with arterial thrombosis on warfarin and aspirin 81 mg and (2) APS patients with arterial thrombosis on warfarin without aspirin.

Adult patients aged ≥18 years, diagnosed with APS (ICD-10: D68.61), had arterial thrombotic events (eg, cerebral infarction, myocardial infarction, arterial embolism), and INR values between 2.0 and 3.0 were included in the study. Those on other antiplatelet or direct oral anticoagulants were excluded. Propensity score matching (1:1) was employed to balance demographics and comorbidities among participants.

The research team evaluated the outcomes, including thrombotic events, bleeding complications, mortality, and healthcare utilization, over 4 years. They also calculated the hazard ratios (HRs) with 95 percent confidence intervals (CIs).

A total of 2,144 patients were included in each cohort following propensity score matching. The mean follow-up duration was 1,479 days in the aspirin group and 1,589 days in the no-aspirin group. In Kaplan-Meier survival analysis, patients who received add-on aspirin had significantly greater risks for several adverse outcomes. [ASH 2025, abstract 952]

Specifically, aspirin users had increased risks of gastrointestinal bleeding (HR, 1.44, 95 percent CI, 1.14‒1.81; p=0.001), hemoperitoneum (HR, 3.20, 95 percent CI, 1.44‒7.13; p=0.003), iron deficiency anaemia (HR, 1.35, 95 percent CI, 1.12‒1.63; p=0.001), and requirement of blood transfusion (HR, 1.34, 95 percent CI, 1.02‒1.77; p=0.037).

Mortality

Moreover, the risk of developing intracranial haemorrhages was 40-percent higher in the aspirin group (HR, 1.40, 95 percent CI, 1.01‒1.93; p=0.041), while those for ischaemic stroke and acute myocardial infarction was higher by 52 percent (HR, 1.52, 95 percent CI, 1.10‒2.08; p=0.009) and 110 percent (HR, 2.10, 95 percent CI, 1.47‒3.00; p<0.001), respectively.

On the other hand, the HR for peripheral arterial events did not reach statistical significance (HR, 1.07, 95 percent CI, 0.68‒1.66; p=0.775).

APS patients who received low-dose aspirin also had greater hospitalization (HR, 1.75, 95 percent CI, 1.34‒2.28; p<0.001), outpatient visits (HR, 1.84, 95 percent CI, 1.27‒2.67; p=0.001), emergency department visits (HR, 1.31, 95 percent CI, 1.11‒1.55; p=0.001).

Notably, all-cause mortality did not significantly differ between the aspirin and no-aspirin groups (HR, 1.02, 95 percent CI, 0.90‒1.16; p=0.779).

“These findings raise important questions about routinely combining aspirin with warfarin in APS patients with arterial thrombosis, as it appears to increase bleeding risk without improving survival,” Khan said.

“Further prospective studies are needed to determine the most effective and safest antithrombotic approach for this high-risk group,” he added.

APS is a major cause of arterial thrombosis and recurrent vascular events and may require lifelong anticoagulation, according to the researchers.