Background: The 2023 ACR/EULAR antiphospholipid syndrome (APS) criteria reduced IgM weighting and introduced a category for isolated lupus anticoagulant (LA), creating uncertainty about primary thromboprophylaxis in aPL carriers with <3 laboratory points.

Objectives: To evaluate the effectiveness and safety of primary thromboprophylaxis in asymptomatic aPL carriers across 2023 ACR/EULAR serological domains, including a subgroup with <3 laboratory points. As a secondary aim, to assess the predictive value of the new ACR/EULAR thrombotic risk profiles.

Methods: All asymptomatic carriers of single or confirmed LA, anticardiolipin (aCL), or anti-β2-glycoprotein I antibodies (anti-β2GPI), between January 2018 and March 2024 were included (n=985). Primary outcomes were thrombotic-free survival (TFS), grade ≥3 bleeding-free survival (BFS), and bleeding symptoms. Logistic and Cox regression models were applied, and Altman–Andersen method estimated the number needed to treat (NNT) and harm (NNH).

Results: During a median follow-up of 2.84 [IQR 1,12-4,74] years, venous (VTE) and arterial (ATE) thromboses occurred in 4.6% and 4.1% of patients, respectively. Among the entire cohort, aspirin (ASA) improved TFS (HR 0.51; p =0.001) without affecting BFS (HR 0.96; p =0.81). P2Y12 inhibitors were associated with higher ATE (OR 13.17; p <0.001) and minor bleeding (OR 4.875; p =0.007). High-risk venous profiles predicted VTE (OR 2.42; p =0.005). Among 458 carriers with <3 laboratory points, ASA remained protective (HR 0.53; p =0.047) without increasing minor or major bleeding. P2Y12 inhibitors showed no benefit in TFS and were linked to decreased BFS (HR 4.211; p =0.008).

Conclusions: Low-dose aspirin may lower thrombotic risk without increasing bleeding in asymptomatic aPL carriers, even in those with <3 laboratory points. P2Y12 inhibitors demonstrated reduced efficacy and an increased risk of bleeding, warranting confirmation in future studies.

Table 1. Benefit–harm balance of primary thromboprophylaxis in antiphospholipid antibody carriers according to ACR/EULAR laboratory points.

(abbreviations: aPL, antiphospholipid antibodies; ASA, acetylsalicylic acid; NNT, number needed to treat; NNH, number needed to harm).

Figure 1.

Multivariable analyses of thrombotic and bleeding outcomes in antiphospholipid antibody carriers with <3 ACR/EULAR laboratory points.

(abbreviations: ATE, arterial thrombotic event; APS, antiphospholipid syndrome; ASA, acetylsalicylic acid; BFS, bleeding-free survival; CI, confidence interval; HR, hazard ratio; OR, odds ratio; TFS, thrombotic-free survival; VTE, venous thromboembolism).

REFERENCES: NIL.

Acknowledgments: NIL.

Disclosure of Interests: None declared.