Low Hydroxychloroquine Exposure Linked to Higher Estimated Atherosclerotic Cardiovascular Risk in Systemic Lupus Erythematosus

A new study suggests that people with systemic lupus erythematosus (SLE) who have inadequate exposure to hydroxychloroquine (HCQ) may have higher estimated atherosclerotic cardiovascular (ASCVD) disease risk. HCQ (known commercially as Plaquenil®) is safe and widely used for more favorable outcomes in people with active disease. Lupus and lupus treatments can cause several problems with the blood and blood vessels, or the veins and arteries that carry blood to and from the heart. Research into the wide-ranging effects of HCQ has revealed many important benefits in the treatment of lupus.  

Researchers followed 248 people with SLE taking HCQ from a single center (the Wisconsin cohort), measuring both their HCQ blood concentrations and prescription refill adherence over about a year. ASCVD risk was estimated using the American Heart Association's PREVENT 10-year risk calculator. They found low HCQ exposure was associated with higher estimated ASCVD risk. People with very low HCQ blood levels (<200 ng/mL) and low medication coverage (<80% of days) had an estimated 10-year ASCVD risk of 6.6%, compared with 4.5% among people with therapeutic HCQ levels (≥750 ng/mL) and higher medication coverage (>80% of days). Declining HCQ exposure over time also mattered. People whose blood levels and medication coverage worsened had an estimated risk of 5.7%, vs. 3.2% among those whose exposure remained stable. Other factors associated with higher ASCVD risk included kidney disease, greater accumulated lupus-related damage, and longer SLE duration. Use of biologics alongside HCQ was associated with relatively lower estimated risk.  

Using PREVENT, the researchers also calculated predicted ASCVD risk. The combination of poor long-term adherence and very low biological exposure was associated with higher predicted ASCVD risk, but this was a one-year, single-center study measuring predicted risks rather than actual cardiovascular events, so larger, multicenter studies measuring actual ASCVD events are needed before concluding that maintaining ≥750 ng/mL directly prevents ASCVD. The researchers argue that prescription refill records alone are not enough to assess adherence. Measuring HCQ blood levels adds information because absorption, metabolism, clearance, and actual pill-taking can all affect how much drug reaches the bloodstream. As such, they suggest aiming for sustained adherence plus therapeutic HCQ blood concentrations of ≥750 ng/mL, which may help optimize ASCVD outcomes and help avoid adding unnecessary preventative medications such as statins—reducing overall pill burden. 

This study underscores that consistent HCQ use and potentially monitoring actual HCQ blood concentrations could be important beyond controlling lupus itself. While this study shows an association, it is not proof that raising HCQ levels will prevent heart attacks or strokes. Talk to your doctor before making any changes to your treatment. This study was supported by grants from the Lupus Foundation of America (Wisconsin Chapter). Learn more about lupus and the heart. 

Read the study