Optimizing Hydroxychloroquine Blood Levels and Long‐Term Hydroxychloroquine Intake Could Lower <scp>ASCVD</scp> Risk and Prevent Polypharmacy in Systemic Lupus Erythematosus

BACKGROUND: Hydroxychloroquine (HCQ) is the cornerstone of systemic lupus erythematosus (SLE) management with benefits extending beyond SLE control, including protection against atherosclerotic cardiovascular disease (ASCVD). While HCQ blood levels reflect recent exposure and long-term intake reflects medication adherence, the impact of longitudinal changes in both measures on ASCVD risk over time remains unclear. We evaluated how HCQ blood levels and long-term intake patterns relate to estimated ASCVD risk at baseline and after one year. METHODS: In this prospective longitudinal study, 248 adults with SLE from the Wisconsin cohort (meeting 2019 ACR/EULAR criteria) taking HCQ and completing baseline and 1-year follow-up visits were included. Long-term HCQ intake was estimated using the proportion of days covered (PDC), and whole-blood HCQ levels served as a marker of recent exposure. Ten-year ASCVD risk was calculated at both time points using the PREVENT calculator. Multivariable linear regression assessed associations between HCQ exposure patterns and ASCVD risk. Changes in exposure categories over one year were also evaluated. RESULTS: Patients with very low HCQ blood levels (<200 ng/mL) and low long-term intake (PDC <80%) had significantly higher ASCVD risk at baseline (+2.1%) with a mean predicted risk of 6.6%. Those who remained in or transitioned into these low-exposure categories over one year had the highest ASCVD risk at follow-up (5.7%). CONCLUSIONS: Maintaining low long-term HCQ intake and very low HCQ blood levels increased ASCVD risk in patients with SLE. Interventions promoting sustained adherence and therapeutic HCQ levels may enhance cardiovascular outcomes and reduce unnecessary preventive therapies.