Consistent efficacy and safety of DOAC in PAD patients with or without CAD
VOYAGER PAD and concomitant coronary artery disease
Presented at the ESC congress 2020 by: William Hiatt, MD (Aurora, CO, USA)
Introduction and methods
Patients with peripheral artery disease (PAD) have an increased risk of major adverse cardiac events (MACE). This risk is even higher in PAD patients with concomitant coronary artery disease (CAD). Previous studies have also shown heterogeneity in response to therapy based on presence or absence of CAD in patients with PAD. The VOYAGER PAD trial randomized 6564 patients with symptomatic lower extremity PAD undergoing peripheral revascularization in a 1:1 ratio to receive either rivaroxaban 2.5 mg twice daily or placebo. All patients received aspirin. The objective of this subgroup analysis of the VOYAGER PAD trial was to evaluate whether presence of CAD is associated with increased risk of MACE and/or major adverse limb events (MALE) compared to absence of CAD in PAD patients. A second objective was to evaluate whether the safety and efficacy of rivaroxaban after lower extremity revascularization is consistent in PAD patients with and without CAD.
The primary outcome of the current subanalysis is the composite of acute limb ischemia, major amputation of vascular etiology, myocardial infarction, ischemic stroke or CV death.
- Baseline characteristics show that PAD patients with concomitant CAD were older and more likely to have CV risk factors including hypertension, diabetes and hyperlipidemia. They were also more likely to have carotid stenosis and heart failure (HF) and to undergo an endovascular revascularization, but slightly less likely to have critical limb ischemia compared to PAD patients without CAD. PAD patients with CAD were also more likely to be on statins and ACEi/ARB compared to those without CAD.
- The cumulative incidence of the primary composite endpoint over almost 3 years in the placebo group was 17.9% in PAD patients without CAD and 24.3% in PAD patients with CAD.
- The HR’s for the comparison between rivaroxaban and placebo for primary composite endpoint for PAD patients with CAD were 0.78 (95%CI 0.64-0.95, ARR 5.4%), and 0.89 (95%CI 0.77-1.04, ARR 1.8%) for PAD patients without CAD. No significant interaction was found (P-interaction=0.29), but the absolute risk reduction was greater in PAD patients with concomitant CAD compared to those without CAD.
- PAD patients with CAD had a HR for the comparison between rivaroxaban and placebo for MI of 0.77 (95%CI 0.55-1.08) and an ARR of 1.5%. Those without CAD had a HR for MI of 0.98 (95%CI 0.70-1.35) and an ARR of 0.5%. When looking at acute limb ischemia (ALI), PAD patients with CAD had a HR of 0.78 (95%CI 0.54-1.14) and an ARR of 1.1%. Those without CAD had a HR for ALI of 0.61 (95%CI 0.49-0.81) and an ARR of 3.1%. No significant interactions were found.
- Risk of intracranial hemorrhage or fatal bleeding were similar in both treatment groups (rivaroxaban vs. placebo) and no interaction was found between subgroups (PAD with CAD and PAD without CAD). Risk for TIMI major bleeding was increased in the rivaroxaban group vs. placebo group in PAD patients with and without CAD (HR 2.24, 95%CI 1.10-4.56 for PAD with CAD and HR 1.15, 95%CI 0.72-1.84 for PAD without CAD). There was no interaction between subgroups (P-interaction 0.13). HR’s for the comparison between rivaroxaban and placebo for ISTH major bleeding in PAD patients with CAD were 1.49 (95%CI 0.95-2.33) and 1.31 (95%CI 1.02-1.90) for PAD patients without CAD. No significant interaction was found.
Efficacy and safety of rivaroxaban 2.5 mg twice daily plus aspirin in PAD patients are consistent regardless of the absence or presence of CAD with no significant interactions.
- Our reporting is based on the information provided at the ESC congress -