This emulated target trial used TriNetX electronic health record data (2020–2025) from 67 healthcare organizations to compare 3-year cardiovascular disease (CVD) risk in adults with SLE initiating anifrolumab vs. belimumab, excluding those with prior CVD. After propensity score matching, 1,084 pairs were analyzed.
Compared with belimumab, anifrolumab was associated with significantly lower 3-year risks across all endpoints: MI (HR 0.63; 95% CI 0.40–0.91), heart failure (HR 0.55; 0.39–0.75), ischemic stroke (HR 0.50; 0.26–0.94), and MACE (HR 0.65; 0.37–0.89).
- Observational design with residual confounding (e.g., unmeasured disease severity, lupus nephritis activity) despite propensity score matching. - Causality cannot be established; prospective RCT data are lacking. - TriNetX data may have coding inconsistencies across 67 organizations.
For SLE patients with elevated CVD risk, anifrolumab may be preferred over belimumab when both are otherwise equally indicated. Clinicians should weigh these observational findings carefully while awaiting prospective confirmation.
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