Effect of Low-Dose Rivaroxaban Plus Aspirin on Carotid Plaque Inflammation (SPIRIT): A Randomized 18F-FDG PET/CT Trial

Background: Aspirin plus rivaroxaban reduces cardiovascular events in patients with stable atherosclerosis; however, whether Factor Xa inhibition attenuates arterial wall inflammation in humans remains unclear. Methods: We conducted a single-center, randomized, open-label, proof-of-concept study with blinded endpoint assessment using 1F-fluorodeoxyglucose positron emission tomography/computed tomography (1F-FDG PET/CT). Adults with asymptomatic carotid stenosis (20-80%) and baseline carotid inflammation (target-to-background ratio [TBR] 1.6) were randomly assigned in a 1:1 ratio to receive either aspirin (100 mg/day) plus rivaroxaban (2.5 mg twice daily) or aspirin (100 mg/day) alone. The primary endpoint was the percent change in the most diseased segment (MDS) TBR of the index carotid artery from baseline to 12 months. Secondary endpoints included whole-vessel carotid TBR, aortic TBR, and changes in lipids and high-sensitivity C-reactive protein. Results: Between September 2021 and December 2023, 92 patients were randomized (mean age 69.4 years; 88% men); 81 (88%) completed 12-month imaging. Mean percent changes in carotid MDS TBR were 7.25% (95% CI, 11.03 to 3.48) and 7.36% (95% CI, 11.06 to 3.67) in the combination therapy and aspirin-alone groups, respectively. The adjusted between-group difference (combination therapy minus aspirin alone) was 1.50 percentage points (95% CI, 6.20 to 3.21; P=0.53). No significant between-group differences were observed in whole-vessel carotid or aortic TBR, or in laboratory parameters. Minor bleeding occurred in four patients (8.7%) receiving combination therapy and in one (2.2%) receiving aspirin alone, with no major bleeding or deaths. Conclusions: In patients with carotid atherosclerosis, adding low-dose rivaroxaban to aspirin did not reduce arterial inflammation beyond aspirin alone over 12 months on 1F-FDG PET/CT.