Effect of low-dose rivaroxaban plus aspirin on 18F-FDG PET/CT-detectable carotid plaque inflammation: a randomized trial.

AIMS: Aspirin plus low-dose rivaroxaban reduces cardiovascular events in stable atherosclerosis; its effect on arterial inflammation in humans remains unclear. We tested whether adding low-dose rivaroxaban to aspirin reduces 18F-fluorodeoxyglucose positron emission tomography/computed tomography (FDG PET/CT)-detectable carotid plaque inflammation.

METHODS AND

RESULTS

In this single-centre, randomized, open-label, proof-of-concept trial with blinded endpoint assessment, adults with asymptomatic carotid stenosis (20-80%) and elevated carotid FDG uptake [target-to-background ratio (TBR) ≥ 1.6] were assigned 1:1 to aspirin (100 mg/day) plus rivaroxaban (2.5 mg twice daily) or aspirin alone. The primary endpoint was per cent change in the most diseased segment (MDS) TBR of the index carotid artery at 12 months. Secondary endpoints included whole-vessel carotid TBR, aortic TBR, lipid and high-sensitivity C-reactive protein (hsCRP) changes. From September 2021 to December 2023, 92 patients were randomized (mean age 69.4 years; 88% men), and 81 (88%) completed paired imaging. Mean per cent changes in MDS TBR were -7.25% [95% confidence interval (CI), -11.03 to -3.48] with combination therapy and -7.36% (95% CI, -11.06 to -3.67) with aspirin alone (adjusted between-group difference, -1.50 percentage points, 95% CI, -6.20 to 3.21; P = 0.529). Secondary imaging endpoints were concordant. Laboratory parameters were similar, except for a nominal hsCRP difference without multiplicity adjustment. Minor bleeding occurred in four (8.7%) and one (2.2%) patients, respectively; no major bleeding or deaths occurred.

CONCLUSION

In patients with carotid atherosclerosis, adding low-dose rivaroxaban to aspirin did not produce a detectable incremental reduction in 18F-FDG PET/CT-assessed carotid plaque inflammation compared with aspirin alone over 12 months.

CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov NCT05797376.