XARELTO® is the first and only therapy indicated for both coronary artery disease (CAD) and PAD, now including PAD patients post-LER

XARELTO® is the only anticoagulant in 20 years to show significant benefit in patients with PAD who remain at high risk for major thrombotic events, including acute limb ischemia and amputation

PAD impacts 20 million Americans1 and is the leading cause of amputations in the U.S., with rates continuing to rise2

RARITAN, NJ, USA I August 24, 2021 I The Janssen Pharmaceutical Companies of Johnson & Johnson today announced that the U.S. Food and Drug Administration (FDA) has approved an expanded peripheral artery disease (PAD) indication for the XARELTO® (rivaroxaban) vascular dose (2.5 mg twice daily plus aspirin 100 mg once daily) to include patients following recent lower-extremity revascularization (LER) due to symptomatic PAD. The approval is based on data from the Phase 3 VOYAGER PAD study. With this approval, XARELTO® is the first and only therapy indicated to help reduce the risks of major cardiovascular (CV) events in patients with coronary artery disease (CAD) and major thrombotic vascular events, such as myocardial infarction, ischemic stroke, acute limb ischemia, and major amputation of a vascular etiology, in patients with PAD, including patients who have recently undergone LER due to symptomatic PAD.

“For more than 20 years, many physicians have used dual antiplatelet therapy after lower extremity revascularization due to symptomatic PAD with limited data to support efficacy and safety in this setting. Now, the VOYAGER PAD and COMPASS clinical studies have demonstrated the utility of dual pathway inhibition in targeting both platelets and thrombin in patients with PAD. These data provide a new mechanism of treatment using an evidence-based strategy for this vulnerable population,” said Marc P. Bonaca*, M.D., M.P.H., Department of Medicine, Division of Cardiovascular Medicine, University of Colorado Anschutz Medical Campus, Aurora, Colorado. “This FDA approval of rivaroxaban plus aspirin is a major advancement for PAD management and sets the stage to evolve the current standard of care for patients with PAD.”

PAD is a common chronic circulatory condition that causes blood vessels to narrow, thereby reducing blood flow to the limbs, most often the legs.3 It is a disease which often goes undiagnosed and undertreated.4 In fact, an estimated 20 million Americans are living with PAD, but only 8.5 million are currently diagnosed.5 While it usually starts asymptomatically, PAD can progress to severe symptoms and require revascularization to avoid amputation.6 PAD is the leading cause of amputations in the U.S. and results in high rates of fatal and non-fatal CV events.6

“PAD is a serious condition that is too frequently missed or often not even discussed by patients and their doctors due to lack of awareness and other health conditions that often take priority. It’s important to understand the risk factors for PAD, including conditions such as diabetes, smoking and high blood pressure,” said Ryan Gough, Executive Director of the Partnership to Advance Cardiovascular Health**, a heart patient advocacy organization. “There’s been a long-standing need across the healthcare community for increased education around PAD and better access to screening and innovative treatments. This is especially critical for patients in underserved communities, who are often at even greater risk for serious complications like amputation.”

Amputations are a devastating complication of PAD and are associated with high mortality, despite being largely preventable.6 In recent years, the rate of amputations in the U.S. has been increasing,7 with studies showing Black Americans – who have a higher prevalence of asymptomatic PAD, less access to quality vascular care6, and are at risk for delays in care8 – are up to four times more likely to have an amputation as a result of PAD compared to White Americans.1

XARELTO® now has nine indications in the U.S. – the most of any direct oral anticoagulant (DOAC). Today’s approval is based on the Phase 3 VOYAGER PAD trial, which demonstrated the XARELTO® vascular dose (2.5 mg twice daily plus aspirin 100 mg once daily) reduced the risk of major adverse limb and cardiovascular events by 15 percent in patients with symptomatic PAD post-LER compared to aspirin alone.9 The VOYAGER PAD trial saw no significant difference in TIMIi major bleeding between XARELTO® with aspirin compared to aspirin alone. The results from the VOYAGER PAD study complement findings from the landmark Phase 3 COMPASS trial, which also examined the dual pathway approach of XARELTO® with aspirin in CAD and/or PAD patients and further supports this FDA label extension in PAD patients.10 Data from the Phase 3 COMPASS trial resulted in FDA approval in 2018 to reduce the risk of major cardiovascular events, such as heart attack, stroke and cardiovascular death in people with chronic PAD and CAD.10 While there were more major bleeds with the XARELTO® vascular dose in COMPASS, there was no significant difference in rates of fatal bleeding, intracranial bleeding or symptomatic bleeding into a critical organ.9,10

“We’re thrilled to bring XARELTO® to even more patients with PAD who have been living for two decades without any new innovation in the antithrombotic space,” said James List, M.D., Ph.D., Global Therapeutic Area Head, Cardiovascular and Metabolism, Janssen Research & Development, LLC. “Today’s approval underscores Janssen’s commitment to transform care for people living with PAD and make XARELTO® available to even more patients in need.”

i Thrombolysis in Myocardial Infarction

The Phase 3 VOYAGER PAD study included 6,564 patients from 542 sites across 34 countries worldwide. Patients were randomized in a 1:1 ratio and received either the XARELTO® vascular dose (2.5 mg twice daily plus aspirin 100 mg once daily) (n=3,286) or aspirin alone (100 mg once daily) (n=3,278). Patients were stratified by revascularization procedure type (endovascular vs. surgical) and use of clopidogrel, which was administered at the treating physician’s discretion. Patients were followed for a median of 28 months.

The VOYAGER PAD study met its primary efficacy and principal safety endpoints, demonstrating the XARELTO® vascular dose was superior to aspirin alone in reducing the risk of major adverse limb and cardiovascular events by 15 percent in patients with symptomatic PAD after lower-extremity revascularization. The benefit of adding XARELTO® to aspirin was apparent early, was consistent among major subgroups and continued to accrue over time. There was no significant increase in TIMI major bleeding observed in patients treated with the XARELTO® vascular dose compared to aspirin alone (2.65 percent vs. 1.87 percent respectively).

COMPASS, the largest clinical study of XARELTO® to date, enrolled a total of 27,395 patients with chronic CAD and/or PAD. Patients were randomized in a 1:1:1 ratio, with one group receiving the XARELTO® vascular dose (2.5 mg twice daily plus aspirin 100 mg once daily), another group receiving rivaroxaban 5 mg twice daily, and the final group receiving aspirin 100 mg once daily. COMPASS was stopped approximately one year ahead of schedule due to efficacy.

COMPASS met its primary efficacy endpoint, with the XARELTO® vascular dose shown to be superior to aspirin alone, reducing major CV events by 24 percent. This finding was driven by a robust 42 percent reduction in any stroke and 22 percent reduction in CV death. While the risk of major bleeding was significantly higher in patients taking the XARELTO® vascular dose compared to aspirin alone, there was no significant difference between the treatment groups in fatal bleeds, intracranial bleeds, symptomatic bleeding into a critical organ, or bleeding into the surgical site requiring reoperation.

XARELTO® is a prescription medicine used to:

  • reduce the risk of stroke and blood clots in people who have a medical condition called atrial fibrillation that is not caused by a heart valve problem. With atrial fibrillation, part of the heart does not beat the way it should. This can lead to the formation of blood clots, which can travel to the brain, causing a stroke, or to other parts of the body
  • treat blood clots in the veins of your legs (deep vein thrombosis or DVT) or lungs (pulmonary embolism or PE)
  • reduce the risk of blood clots happening again in people who continue to be at risk for DVT or PE after receiving treatment for blood clots for at least 6 months
  • help prevent a blood clot in the legs and lungs of people who have just had hip or knee replacement surgery
  • help prevent blood clots in certain people hospitalized for an acute illness and after discharge, who are at risk of getting blood clots because of the loss of or decreased ability to move around (mobility) and other risks for getting blood clots, and who do not have a high risk of bleeding

XARELTO® is used with low dose aspirin to:

  • reduce the risk of serious heart problems, heart attack and stroke in people with coronary artery disease (a condition where the blood supply to the heart is reduced or blocked)
  • reduce the risk of a sudden decrease in blood flow to the legs, major amputation, serious heart problems or stroke in people with peripheral artery disease (a condition where the blood flow to the legs is reduced), and includes people who have recently had a procedure to improve blood flow to the legs

It is not known if XARELTO® is safe and effective in children.

About Janssen Cardiovascular & Metabolism
In Cardiovascular & Metabolism (CVM), we take on the most pervasive diseases that burden hundreds of millions of people and healthcare systems around the world. As part of this long-standing commitment and propelled by our successes in treating type 2 diabetes and thrombosis, we advance highly differentiated therapies that prevent and treat life-threatening cardiovascular, metabolic and retinal diseases. Uncovering new therapies that can improve the quality of life for this large segment of the population is an important endeavor – one which Janssen CVM will continue to lead in the years to come. Our mission is global, local and personal. Together, we can reshape the future of cardiovascular, metabolic and retinal disease prevention and treatment. Please visit www.janssen.com/cardiovascular-and-metabolism.

About the Janssen Pharmaceutical Companies of Johnson & Johnson
At Janssen, we’re creating a future where disease is a thing of the past. We’re the Pharmaceutical Companies of Johnson & Johnson, working tirelessly to make that future a reality for patients everywhere by fighting sickness with science, improving access with ingenuity, and healing hopelessness with heart. We focus on areas of medicine where we can make the biggest difference: Cardiovascular & Metabolism, Immunology, Infectious Diseases & Vaccines, Neuroscience, Oncology, and Pulmonary Hypertension. Learn more at www.janssen.com. Follow us at www.twitter.com/JanssenUS and www.twitter.com/JanssenGlobal. Janssen Research & Development, LLC, is part of the Janssen Pharmaceutical Companies of Johnson & Johnson.

1. Racial Disparities in Vascular Care. (n.d.). Retrieved June 17, 2021 from https://cardiovascularcoalition.com/our-patients/racial-disparities-in-vascular-care/.
2. Norgren L, Hiatt WR, Dormandy JA, Hirsch AT, et al. The next 10 years in the management of peripheral artery disease: perspectives from the ‘PAD 2009’ Conference. Eur Vasc Endovasc Surg. 2010;40(3):375-380.
3. American Heart Association. About Peripheral Artery Disease (PAD). Retrieved April 29, 2021 from https://www.heart.org/en/health-topics/peripheral-artery-disease/about-peripheral-artery-disease-pad.
4. Afzal N, Sohn S, Scott CG, Liu H, Kullo IJ, Arruda-Olson AM. Surveillance of peripheral arterial disease cases using natural language processing of clinical notes. AMIA Jt Summits Transl Sci Proc. 2017;2017:28-36. Retrieved June 2, 2021 from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5543345/#r2-2609862.
5. American Heart Association. Peripheral Artery Disease (PAD) Resources For Patients and Providers. Retrieved April 29, 2021 from https://www.heart.org/en/health-topics/peripheral-artery-disease/pad-resources.
6. Creager MA, Matsushita K, Arya S, et al. Reducing nontraumatic lower-extremity amputations by 20% by 2030: time to get to our feet: a policy statement from the American Heart Association. Circulation. 2021;143(17):e875-e891. doi:10.1161/CIR.000000000000096.
7. Schuivens PME, Buijs M, Boonman-de Winter L, et al. Impact of the COVID-19 lockdown strategy on vascular surgery practice: more major amputations than usual. Ann Vasc Surg. 2020;69:74-79. doi:10.1016/j.avsg.2020.07.025. Retrieved June 2, 2021 from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7402273/.
8. Winta Ghidei, Tracie C. Collins, “African Americans and Peripheral Arterial Disease: A Review Article”, International Scholarly Research Notices, vol. 2012, Article ID 165653, 9 pages, 2012. https://doi.org/10.5402/2012/165653
9. Bonaca MP, Bauersachs RM, Anand SS, et al. Rivaroxaban in peripheral artery disease after revascularization. N Engl J Med. 2020 May 21;382(21):1994-2004.
10. Eikelboom JW, Connolly SJ, Bosch J, et al. Rivaroxaban with or without aspirin in stable cardiovascular disease. N Engl J Med. 2017 Oct 5;377:1319-1330.

*Dr. Bonaca is affiliated with CPC Clinical Research, which was provided a grant for their participation in the Phase 3 VOYAGER PAD clinical trial.
**The Partnership to Advance Cardiovascular Health was provided a grant to help support their PAD disease awareness program.