A pre-specified analysis of the VOYAGER PAD study showed that diabetic patients with symptomatic peripheral artery disease (PAD) who had just undergone peripheral artery revascularisation have a similar treatment benefit from low-dose rivaroxaban compared with non-diabetics. However, both their rate of treatment discontinuation and their risk of TIMI major bleeding are higher than in non-diabetic patients.
The VOYAGER PAD (NCT02504216) study presented a groundbreaking advance for PAD patients who had just undergone peripheral artery revascularisation, who previously had no evidence-based treatment available. In this study, including almost 6,600 patients, the combined antithrombotic regimen of rivaroxaban plus aspirin was safe and effective for reducing ischaemic events in this patient population with an absolute risk reduction of 2.6%. With their pre-specified analysis, Prof. Cecilia Low Wang (University of Colorado, CO, USA) and colleagues aimed to characterise the risk profile of this patient population based on diabetes status at baseline.
Subjects with diabetes at baseline had a different baseline risk with more hypertension, coronary artery disease, a worse kidney function and more clopidogrel use compared with non-diabetics. “We found that among the placebo group the Kaplan Mayer estimate of the primary outcome at 3 years was 22.5% in those with diabetes and 18.2% in non-diabetes,” Prof. Low Wang said. There was also a dramatic difference between diabetics and non-diabetic patients in all-cause mortality: 12.9% of patients with diabetes compared with 9.6% of patients without diabetes randomised to placebo died within 3 years. The hazard ratio for the primary endpoint in patients with diabetes was 0.94, which was consistent with the overall population. The P-value of interaction for diabetes was not significant (0.16).
“This analysis shows that although there is a numerically lower absolute risk reduction [in diabetics] there is no diabetes interaction and effect modification of diabetes,” Prof. Low Wang explained. The overall efficacy of low-dose rivaroxaban was consistent independent of diabetes state.
The higher rate of discontinuation observed in diabetic patients may have attenuated the observed benefit in the intention-to-treat analysis. However, the risk of TIMI major bleeding was significantly greater in diabetic patients, possibly driven by the different baseline risk associated with bleeding: A higher percentage of patients with diabetes had a high bleeding risk at baseline compared with non-diabetics. As Prof. Wang emphasised, one should be aware that there were very few events of major bleedings overall. With regard to intracranial or fatal bleeding, there was no major difference between the groups.
Additional analyses are planned to understand the impact of competing risks, for example hospitalisations to foster optimal patient selection for intensive prevention therapy.
1. Low Wang C. VOYAGER PAD – rivaroxaban in symptomatic PAD with and without comorbid diabetes. Latest science in special populations, ESC Congress 2021, 27–30 August.