Disclosures: The VOYAGER PAD trial was supported by a grant from Bayer AG and Janssen Research and Development. Hsia reports she owns stock in AstraZeneca and has received grant support from Amgen, AstraZeneca and Janssen. Please see the study for all other authors’ relevant financial disclosures.
August 16, 2021
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Rivaroxaban reduces limb events after revascularization in patients with renal impairment

Disclosures: The VOYAGER PAD trial was supported by a grant from Bayer AG and Janssen Research and Development. Hsia reports she owns stock in AstraZeneca and has received grant support from Amgen, AstraZeneca and Janssen. Please see the study for all other authors’ relevant financial disclosures.
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In a cohort of patients with renal impairment who underwent peripheral revascularization, rivaroxaban reduced the primary composite endpoint, driven by a marked reduction in limb events, according to data from the VOYAGER PAD trial.

“Rivaroxaban was clearly beneficial in patients with chronic kidney disease and was particularly effective at reducing the risk of limb events in patients — that is, acute limb ischemia and above-the-knee amputation,” Judith Hsia, MD, with the department of medicine at University of Colorado School of Medicine, told Healio.

people as kidneys
Source: Adobe Stock

Hsia said two catalysts drove the researchers to conduct this substudy of the VOYAGER PAD trial: the prevalence of renal impairment in patients with peripheral artery disease and the increased rivaroxaban (Xarelto, Janssen/Bayer) blood levels in patients with renal impairment.

“One might anticipate greater efficacy and potentially a higher risk of bleeding among patients with renal impairment treated with rivaroxaban,” Hsia said. “Since VOYAGER PAD showed overall improvement in clinical outcomes with rivaroxaban in patients with recent lower extremity revascularization and a low rate of bleeding, we wanted to provide data enabling practitioners to make informed decisions regarding management of their patients with comorbid chronic kidney disease.”

Hsia and colleagues randomly assigned patients who underwent recent peripheral revascularization to rivaroxaban 2.5 mg twice daily or placebo in addition to 100 mg aspirin daily. They defined the primary endpoint as a composite of MI, ischemic stroke, CV death, acute limb ischemia and major amputation.

The analysis included 6,319 patients with an estimated glomerular filtration rate (eGFR) determined at baseline: 6.6% had eGFR less than 45 mL/min/1.73 m2 and 14.4% had eGFR of 45 mL/min/1.73 m2 to less than 60 mL/min/1.73 m2. Overall, female sex, older age and a higher prevalence of CV risk factors, with the exception of smoking, increased the risk for poorer renal function.

Researchers found that rivaroxaban decreased primary endpoint events with no heterogeneity by eGFR category, a result driven by a reduction in major limb events; the HRs were as follows: 0.49 (95% CI, 0.23-1.06) for eGFR less than 45 mL/min/1.73 m2; 0.59 (95% CI, 0.35-1.02) for eGFR of 45 mL/min/1.73 m2 to 59 mL/min/1.73 m2; and 0.77 (95% CI, 0.64-0.94) for eGFR of at least 60 mL/min/1.73 m2 (P = .26 across categories).

“This [reduction in limb events] might be expected as rivaroxaban levels have been shown to be higher in patients with renal impairment,” Hsia said. “In VOYAGER PAD, patients with chronic kidney disease stage 3a or 4 had a 51% reduction in acute limb ischemia and above-the-knee amputation with rivaroxaban compared with placebo. Acute limb ischemia is analogous to acute coronary syndrome; it’s a very high-risk condition that predicts recurrent lower extremity revascularization, amputation and death. So these limb events are clinically meaningful to patients.”

When examining bleeding, Hsia and colleagues similarly found no formal heterogeneity by eGFR category; however, numerically more bleeding occurred with an eGFR less than 45 mL/min/1.73 m2. There was no increase in intracerebral or fatal hemorrhage.

“For patients undergoing lower extremity revascularization, including those with chronic kidney disease stage 2 to 4, rivaroxaban is a postprocedural treatment option to lower the risk of acute limb ischemia and amputation,” Hsia said.

For more information:

Judith Hsia, MD, can be reached at judith.hsia@cpcmed.org.