Data from New VOYAGER PAD Analyses at ACC.22 Reinforce Benefit of XARELTO® (rivaroxaban) Plus Aspirin in Patients with Peripheral Artery Disease (PAD) and Various Co-Morbid Conditions
An analysis showed benefit of XARELTO® plus aspirin in reducing thrombotic hospitalizations for PAD patients with and without chronic kidney disease (CKD)
A separate analysis demonstrated PAD patients who received XARELTO® plus aspirin in addition to statin therapy had the lowest risk of the composite of major adverse cardiovascular events (MACE) or major adverse limb events (MALE) compared to all other treatment groups in the study
RARITAN, N.J., April 1, 2022 – The Janssen Pharmaceutical Companies of Johnson & Johnson today announced data from new analyses from the Phase 3 VOYAGER PAD clinical trial reinforcing the benefit of the XARELTO® (rivaroxaban) vascular dose (2.5 mg twice daily plus aspirin 100 mg once daily) in reducing severe vascular events in patients with PAD after lower-extremity revascularization (LER), a procedure that restores blood flow to the legs. Data from the two analyses demonstrate the role that the XARELTO® vascular dose plays in PAD patients with and without chronic kidney disease (CKD) and in PAD patients with and without a history of statin therapy. Results will be featured at the American College of Cardiology’s 71st Annual Scientific Session (ACC.22), hosted in Washington, D.C. and virtually from April 2-4, 2022. Janssen is committed to investing in studies to transform care and address the high unmet needs of people living with PAD.
Cardiovascular disease, also known as heart disease, can affect more than just the heart. One lesser known but serious condition is PAD, a common, chronic circulatory condition that causes blood vessels to narrow, thereby reducing blood flow to the limbs, and most often the legs.1 It is a disease that often goes undiagnosed and undertreated.2 In the U.S., PAD affects an estimated 20 million adults, yet only approximately 8.5 million are diagnosed.3,4 While it usually starts asymptomatically, PAD can progress to severe symptoms and require revascularization—a surgical procedure that restores blood flow after arteries have been clogged—to avoid amputation.5
“At Janssen, we are continuing to invest in clinical research to help evolve the standard of care for people living with serious cardiovascular diseases, like PAD, an area of critical unmet need,” said James F. List, M.D., Ph.D., Global Therapeutic Area Head, Cardiovascular, Metabolism, and Retina, Janssen Research & Development, LLC. “Our research continues to support the use of the XARELTO® vascular dose and is a treatment option physicians should consider for patients with PAD or coronary artery disease.”
Role of the XARELTO® vascular dose in reducing hospitalizations due to thrombotic events in PAD patients with and without CKD
Some co-morbid conditions put patients at a higher risk of PAD; in fact, patients with CKD have a higher prevalence of PAD, at 24-32 percent, with associated higher six-month rehospitalization rates compared to those without renal impairment.6 In the VOYAGER PAD trial, the XARELTO® vascular dose (2.5 mg twice daily plus aspirin 100 mg once daily) significantly reduced hospitalizations due to thrombotic events in patients who underwent LER, compared to patients who took aspirin alone (Kaplan-Meier estimate at 3 years: 8.7% vs. 12.1%). The results of a VOYAGER PAD subgroup analysis of patients with and without CKD, to be presented as an oral presentation on April 3 (Abstract #906-06), show a consistent 4.7 percent absolute risk reduction (ARR) in the subgroup with CKD with XARELTO® plus aspirin compared to aspirin alone (Kaplan-Meier estimate at 3 years: 7.9% vs. 12.6%).
“Patients with symptomatic PAD are already at a heightened risk of hospitalization following revascularization,” said Mark Svet, M.D., Internal Medicine Resident, University of Colorado Anschutz School of Medicine and lead study author.* “Previously reported primary data from the VOYAGER PAD clinical trial established the benefit of XARELTO® plus aspirin in patients with PAD. Our research demonstrates the extension of this benefit to PAD patients with CKD in reducing rates of readmission following revascularization without increasing bleeding risk compared to those without CKD.”
Effect of the XARELTO® vascular dose and statin therapy in high-risk patients
High cholesterol is another co-morbid condition that can harm a person’s arteries, and raises the risk of PAD.7 If high cholesterol isn’t controlled, a patient is more likely to have PAD and other blood vessel problems.7 An additional VOYAGER PAD analysis to be presented in a moderated poster presentation on April 2 (Abstract #1024-11) at ACC.22 evaluated PAD patients with and without a history of statin use, a therapy commonly prescribed to lower cholesterol levels and reduce the risk of heart attack and stroke.8 Consistent with the overall VOYAGER PAD clinical trial results, the analysis showed that patients with PAD post-LER who received the XARELTO® vascular dose (2.5 mg twice daily plus aspirin 100 mg once daily) and statin therapy had a 19 percent reduction in the primary endpoint composite of acute limb ischemia (ALI), major amputation for vascular cause, myocardial infarction, ischemic stroke or cardiovascular death; a 26 percent reduction of major adverse limb events (MALE); and a 32 percent reduction of acute limb injury versus placebo and statin therapy. Overall, it was found that with or without statin therapy, the XARELTO® vascular dose consistently reduced the composite of major adverse cardiovascular events (MACE) or MALE after revascularization for PAD.
Both analyses showed a numerical but not statistically significant increase in thrombolysis in myocardial infarction (TIMI) major bleeding in patients treated with XARELTO® plus aspirin versus aspirin alone, consistent with the primary results of VOYAGER PAD, regardless of CKD at baseline or statin history. There was no increased intracerebral hemorrhage (ICH) or fatal bleeding with XARELTO® plus aspirin in PAD patients with or without CKD.
In August 2021, the U.S. Food and Drug Administration (FDA) approved an expanded PAD indication for the XARELTO® vascular dose (2.5 mg twice daily plus aspirin 100 mg once daily) to include patients following recent LER due to symptomatic PAD. The XARELTO® vascular dose is the first and only approved treatment for PAD using a dual pathway inhibition (DPI) approach to target both clotting mechanisms, thrombin and platelet activation.
About VOYAGER PAD
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 LER. 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 (Kaplan-Meier estimate at 3 years 2.65% vs. 1.87%, respectively).
WHAT IS XARELTO® (rivaroxaban)?
XARELTO® is a prescription medicine used to:
- reduce the risk of stroke and blood clots in adults 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
XARELTO® is used with low dose aspirin to:
XARELTO® is used in children to:
XARELTO® was not studied and is not recommended in children less than 6 months of age who:
IMPORTANT SAFETY INFORMATION
WHAT IS THE MOST IMPORTANT INFORMATION I SHOULD KNOW ABOUT XARELTO®?
XARELTO® may cause serious side effects, including:
Do not stop taking XARELTO® without talking to the doctor who prescribes it for you. Stopping XARELTO® increases your risk of having a stroke. If you have to stop taking XARELTO®, your doctor may prescribe another blood thinner medicine to prevent a blood clot from forming.
You may have a higher risk of bleeding if you take XARELTO® and take other medicines that increase your risk of bleeding, including:
Tell your doctor if you take any of these medicines. Ask your doctor or pharmacist if you are not sure if your medicine is one listed above.
Call your doctor or get medical help right away if you or your child develop any of these signs or symptoms of bleeding:
If you take XARELTO® and receive spinal anesthesia or have a spinal puncture, your doctor should watch you closely for symptoms of spinal or epidural blood clots.
Tell your doctor right away if you have:
XARELTO® is not for use in people with artificial heart valves.
XARELTO® is not for use in people with antiphospholipid syndrome (APS), especially with positive triple antibody testing.
Do not take XARELTO® if you or your child:
Before taking XARELTO®, tell your doctor about all your medical conditions, including if you or your child:
Tell all of your doctors and dentists that you or your child are taking XARELTO®. They should talk to the doctor who prescribed XARELTO® for you before you have any surgery, medical or dental procedure.
Tell your doctor about all the medicines you or your child take, including prescription and over-the-counter medicines, vitamins, and herbal supplements.
Some of your other medicines may affect the way XARELTO® works, causing side effects. Certain medicines may increase your risk of bleeding. See “What is the most important information I should know about XARELTO®?”
HOW SHOULD I TAKE XARELTO®?
If you take XARELTO® for:
For children who take XARELTO®:
WHAT ARE THE POSSIBLE SIDE EFFECTS OF XARELTO®?
XARELTO® may cause serious side effects:
The most common side effect of XARELTO® in adults was bleeding.
The most common side effects of XARELTO® in children include:
Call your doctor for medical advice about side effects. You may report side effects to the FDA at 1-800-FDA-1088. You may also report side effects to Janssen Pharmaceuticals, Inc., at 1-800-JANSSEN (1-800-526-7736).
Trademarks are those of their respective owners. Janssen and Bayer together are developing rivaroxaban.
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 https://twitter.com/JanssenGlobal. Janssen Research & Development, LLC is part of the Janssen Pharmaceutical Companies of Johnson & Johnson.
Cautions Concerning Forward-Looking Statements
This press release contains “forward-looking statements” as defined in the Private Securities Litigation Reform Act of 1995 regarding product development and the potential benefits and treatment impact of rivaroxaban. The reader is cautioned not to rely on these forward-looking statements. These statements are based on current expectations of future events. If underlying assumptions prove inaccurate or known or unknown risks or uncertainties materialize, actual results could vary materially from the expectations and projections of Janssen Research & Development, LLC, any of the other Janssen Pharmaceutical Companies and/or Johnson & Johnson. Risks and uncertainties include, but are not limited to: challenges and uncertainties inherent in product research and development, including the uncertainty of clinical success and of obtaining regulatory approvals; uncertainty of commercial success; manufacturing difficulties and delays; competition, including technological advances, new products and patents attained by competitors; challenges to patents; product efficacy or safety concerns resulting in product recalls or regulatory action; changes in behavior and spending patterns of purchasers of health care products and services; changes to applicable laws and regulations, including global health care reforms; and trends toward health care cost containment. A further list and descriptions of these risks, uncertainties and other factors can be found in Johnson & Johnson’s Annual Report on Form 10-K for the fiscal year ended January 2, 2022, including in the sections captioned “Cautionary Note Regarding Forward-Looking Statements” and “Item 1A. Risk Factors,” and in Johnson & Johnson’s subsequent Quarterly Reports on Form 10-Q and other filings with the Securities and Exchange Commission. Copies of these filings are available online at www.sec.gov, www.jnj.com or on request from Johnson & Johnson. None of the Janssen Pharmaceutical Companies nor Johnson & Johnson undertakes to update any forward-looking statement as a result of new information or future events or developments.
1. American Heart Association. About Peripheral Artery Disease (PAD). Accessed March 16, 2022 from https://www.heart.org/en/health-topics/peripheral-artery-disease/about-peripheral-artery-disease-pad
2. 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.
3. Racial Disparities in Vascular Care. (n.d.). Accessed March 16, 2022 from https://cardiovascularcoalition.com/ourpatients/racial-disparities-in-vascular-care/
4. American Heart Association. PAD Toolkit for Health Care Professionals. Accessed March 16, 2022, from https://www.heart.org/en/health-topics/peripheral-artery-disease/pad-toolkit
5. 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.
6. Svet M, Hsia J, Patel MR, et al. Rivaroxaban reduces hospitalizations for thromboembolic events in patients with peripheral artery disease after revascularization in those with and without chronic kidney disease. Presented at: The American College of Cardiology’s 71st Annual Scientific Sessions & Expo; April 2022; Washington, D.C.
7. Saint Luke’s. High Cholesterol and Peripheral Arterial Disease (PAD). Accessed March 22, 2022 from https://www.saintlukeskc.org/health-library/high-cholesterol-and-peripheral-arterial-disease-pad
8. Mayo Clinic. Statin Side Effects: Weigh the Benefits and Risks. Accessed March 16, 2022 from
*Dr. Mark Svet is the lead study author of the VOYAGER PAD sub-analysis titled ‘Rivaroxaban Reduces Hospitalizations for Thromboembolic Events in Patients with Peripheral Artery Disease After Revascularization in those with and without Chronic Kidney Disease’ and was provided payment for his participation.
** Thrombolysis in Myocardial Infarction