The Effect of Puerarin on Carotid Intima-Media Thickness in Patients With Active Rheumatoid Arthritis: A Randomized Controlled Trial.

PURPOSE: Cardiovascular and diabetic complications are the main causes of death in patients with rheumatoid arthritis (RA). Puerarin has potential protective effects against subclinical atherosclerosis and insulin resistance, but the clinical evidence is still not sufficient to draw definitive conclusions. Therefore, we performed the clinical trial to assess the effect of puerarin on carotid intima-media thickness (CIMT) in RA.

METHODS: This is an open, controlled, randomized, and parallel-group comparison study of 119 patients with a definite diagnose of active RA. All 119 consecutive patients with RA receiving routine antirheumatic care were randomized to receive treatment with (n = 60; 16 males and 44 females; mean age, 52.97 years; 95% CI, 49.78-56.15 years) or without (n = 59; 17 males and 42 females; mean age, 54.05 years; 95% CI, 50.03-58.07 years) 400mg of puerarin. The effects of both interventions on CIMT, homeostasis model assessment of insulin resistance (HOMA-IR) value, and possible adverse events were assessed and compared at entry, 12 weeks, and 24 weeks. The collected data were processed and assessed using ANCOVA, paired t test, repeated-measure ANOVA, one-way ANOVA, Pearson's χ2 test, Fisher exact test, Kaplan-Meier survival analysis, Pearson correlation, and LOESS (locally weighted smoothing) regression analysis.

FINDINGS: No significant adverse effects occurred concerning the use of puerarin, and both interventions were generally well tolerated in all the patients. A tiny but significant decrease of CIMT was observed in puerarin-treated patients at 24 weeks (-0.003 mm; 95% CI, -0.005 to -0.001vs 0.019 mm; 95% CI, -0.002 to 0.040; P < 0.001). At 24 weeks, insulin resistance was indicated with more pronounced improvement in the puerarin group versus the control group (homeostasis model assessment, -0.40; 95% CI, -0.47 to -0.33vs -0.05; 95% CI, -0.08 to -0.01; P < 0.001). Correlation analysis indicated an interaction between the parallel reductions in CIMT and insulin resistance in the puerarin group (r = 0.878, P < 0.001) but not in the control group.

IMPLICATIONS: In the study, 24 weeks of treatment with 400mg of puerarin exerted a significant effect against CIMT progression in patients with active RA, which may be associated with the improvement of insulin resistance. Puerarin holds promise as a drug candidate for the prevention and treatment of cardiometabolic comorbidities in patients with active RA. However, more strictly designed trials, such as double-blind and placebo-controlled trials, are still required. ClinicalTrials.gov identifier: NCT02254655.