MedicalResearch.com Interview with:
Paul Burton, MD, PhD, FACC
Vice President, Medical Affairs
MedicalResearch.com: What is the background for this study? What are the main findings?
Response: Venous thromboembolism (VTE), which includes deep vein thrombosis (DVT) and pulmonary embolism (PE), affects more than 900,000 Americans each year; one-third of these occurrences are fatal. Once a person experiences a VTE, they are at risk of having another occurrence. Guidelines currently recommend anticoagulant therapy with a non-vitamin K antagonist oral anticoagulant (NOAC), like XARELTO® (rivaroxaban), for three months or longer. Once anticoagulant therapy is stopped, up to 10 percent of people will experience a recurrence during the first year and up to 20 percent within three years. In people who decide to stop anticoagulant therapy, guidelines currently suggest using aspirin for long-term prevention of recurrent VTE rather than no aspirin at all.
The Phase 3 EINSTEIN CHOICE study was designed to compare the efficacy and safety of XARELTO® to aspirin for continued VTE management in people who experienced an initial VTE. The study met its primary endpoint, finding both XARELTO® doses (10 mg or 20 mg once daily) to be superior to aspirin 100 mg once daily in preventing recurrent VTE, with no significant impact on safety. Specifically, XARELTO® 10 mg reduced the risk of recurrent VTE by 74 percent and XARELTO® 20 mg by 66 percent. Rates of major bleeding were comparable and low across all treatment groups.
These results were presented at the American College of Cardiology’s 64th Annual Scientific Session (ACC.17) during a Joint ACC/Journal of American Medical Association Late-Breaking Clinical Trials session and published simultaneously in The New England Journal of Medicine.
MedicalResearch.com: What should readers take away from your report?
Response: In addition to confirming findings from previous studies examining long-term use of XARELTO® in VTE, these robust data from EINSTEIN CHOICE provide us with clinical evidence for the first time that show extended treatment with XARELTO® is superior to aspirin in preventing recurrent VTE, with no significant impact on safety. Potentially, these important data could trigger a shift in the way physicians manage their patients with Venous thromboembolism over the long term.
EINSTEIN CHOICE validates what Janssen is committed to achieving through our industry-leading EXPLORER clinical research program: to uncover the potential of XARELTO® in areas of critical unmet medical need. The EXPLORER program is unmatched by any oral anticoagulant in the NOAC class in its size, scope and ambition. A collaborative effort between Bayer and Janssen, EXPLORER seeks to generate important clinical evidence on the safety and efficacy of XARELTO® and its potential role in addressing critical unmet medical needs. A number of the studies are designed to seek additional indications or to expand the label. By the time of its completion, more than 275,000 patients will have participated in the EXPLORER clinical development program, other completed and ongoing clinical trials, investigative registries and non-interventional studies.
MedicalResearch.com: What recommendations do you have for future research as a result of this study?
Response: Venous thromboembolism represents a tremendous burden to our healthcare systems and PE specifically is a top priority by the Centers for Medicare and Medicaid Services. Additional research is underway to estimate the healthcare costs associated with managing the patients in EINSTEIN CHOICE who experienced events based on primary efficacy. In the meantime, we look forward to discussing the primary findings of EINSTEIN CHOICE with the U.S. Food and Drug Administration (FDA).
MedicalResearch.com: Is there anything else you would like to add?
Response: In addition to providing valuable clinical insights on the superiority of XARELTO® to aspirin, EINSTEIN CHOICE demonstrates the potential use of a lower dose of XARELTO® for extended venous protection.
Also, it’s important to note patients who required extended anticoagulation at therapeutic doses were not included in EINSTEIN CHOICE, as the objective of the study was to investigate those patients for whom the treating physician was uncertain about the need for continuing anticoagulant therapy.
MedicalResearch.com: Thank you for your contribution to the MedicalResearch.com community.
Jeffrey I. Weitz, M.D., Anthonie W.A. Lensing, M.D., Ph.D., Martin H. Prins, M.D., Ph.D., Rupert Bauersachs, M.D., Jan Beyer-Westendorf, M.D., Henri Bounameaux, M.D., Timothy A. Brighton, M.D., Alexander T. Cohen, M.D., Bruce L. Davidson, M.D., M.P.H., Hervé Decousus, M.D., Maria C.S. Freitas, M.D., Ph.D., Gerlind Holberg, V.D., Ph.D., Ajay K. Kakkar, M.B., B.S., Ph.D., Lloyd Haskell, M.D., Bonno van Bellen, M.D., Akos F. Pap, M.Sc., Scott D. Berkowitz, M.D., Peter Verhamme, M.D., Philip S. Wells, M.D., and Paolo Prandoni, M.D., Ph.D., for the EINSTEIN CHOICE Investigators*
March 18, 2017 DOI: 10.1056/NEJMoa1700518
Below please find additional information regarding XARELTO®
XARELTO® is a prescription medicine used to reduce the risk of stroke and blood clots in people with atrial fibrillation, not caused by a heart valve problem. For patients currently well managed on warfarin, there is limited information on how XARELTO® and warfarin compare in reducing the risk of stroke.
XARELTO® is also a prescription medicine used to treat deep vein thrombosis and pulmonary embolism, and to help reduce the risk of these conditions occurring again.
XARELTO® is also a prescription medicine used to reduce the risk of forming a blood clot in the legs and lungs of people who have just had knee or hip replacement surgery.
IMPORTANT SAFETY INFORMATION
WHAT IS THE MOST IMPORTANT INFORMATION I SHOULD KNOW ABOUT XARELTO®?
- For people taking XARELTO®for atrial fibrillation:
People with atrial fibrillation (an irregular heart beat) are at an increased risk of forming a blood clot in the heart, which can travel to the brain, causing a stroke, or to other parts of the body. XARELTO® lowers your chance of having a stroke by helping to prevent clots from forming. If you stop taking XARELTO®, you may have increased risk of forming a clot in your blood.
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.
- XARELTO® can cause bleeding, which can be serious, and rarely may lead to death. This is because XARELTO® is a blood thinner medicine that reduces blood clotting. While you take XARELTO® you are likely to bruise more easily and it may take longer for bleeding to stop.
You may have a higher risk of bleeding if you take XARELTO® and take other medicines that increase your risk of bleeding, including:
- Aspirin or aspirin-containing products
- Non-steroidal anti-inflammatory drugs (NSAIDs)
- Warfarin sodium (Coumadin®, Jantoven®)
- Any medicine that contains heparin
- Clopidogrel (Plavix®)
- Selective serotonin reuptake inhibitors (SSRIs) or serotonin norepinephrine reuptake inhibitors (SNRIs)
- Other medicines to prevent or treat blood clots
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 develop any of these signs or symptoms of bleeding:
- Unexpected bleeding or bleeding that lasts a long time, such as:
- o Nosebleeds that happen often
- o Unusual bleeding from gums
- o Menstrual bleeding that is heavier than normal, or vaginal bleeding
- Bleeding that is severe or that you cannot control
- Red, pink, or brown urine
- Bright red or black stools (looks like tar)
- Cough up blood or blood clots
- Vomit blood or your vomit looks like “coffee grounds”
- Headaches, feeling dizzy or weak
- Pain, swelling, or new drainage at wound sites
Spinal or epidural blood clots (hematoma): People who take a blood thinner medicine (anticoagulant) like XARELTO®, and have medicine injected into their spinal and epidural area, or have a spinal puncture, have a risk of forming a blood clot that can cause long-term or permanent loss of the ability to move (paralysis). Your risk of developing a spinal or epidural blood clot is higher if:
- A thin tube called an epidural catheter is placed in your back to give you certain medicine
- You take NSAIDs or a medicine to prevent blood from clotting
- You have a history of difficult or repeated epidural or spinal punctures
- You have a history of problems with your spine or have had surgery on your spine
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 back pain, tingling, numbness, muscle weakness, (especially in your legs and feet), or loss of control of the bowels or bladder (incontinence).
XARELTO® is not for patients with artificial heart valves.
WHO SHOULD NOT TAKE XARELTO®?
Do not take XARELTO® if you:
- Currently have certain types of abnormal bleeding. Talk to your doctor before taking XARELTO® if you currently have unusual bleeding.
- Are allergic to rivaroxaban or any of the ingredients of XARELTO®.
WHAT SHOULD I TELL MY DOCTOR BEFORE OR WHILE TAKING XARELTO®?
Before taking XARELTO®, tell your doctor if you:
- Have ever had bleeding problems
- Have liver or kidney problems
- Have any other medical condition
- Are pregnant or plan to become pregnant. It is not known if XARELTO®will harm your unborn baby. Tell your doctor right away if you become pregnant while taking XARELTO®. If you take XARELTO®during pregnancy, tell your doctor right away if you have bleeding or symptoms of blood loss.
- Are breastfeeding or plan to breastfeed. It is not known if XARELTO®passes into your breast milk. You and your doctor should decide if you will take XARELTO®or breastfeed.
Tell all of your doctors and dentists that you 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 take, including prescription and nonprescription medicines, vitamins, and herbal supplements. Some of your other medicines may affect the way XARELTO® works. Certain medicines may increase your risk of bleeding. See “What is the most important information I should know about XARELTO®?”
Especially tell your doctor if you take:
- Ketoconazole (Nizoral®)
- Itraconazole (Onmel™, Sporanox®)
- Ritonavir (Norvir®)
- Lopinavir/ritonavir (Kaletra®)
- Indinavir (Crixivan®)
- Carbamazepine (Carbatrol®, Equetro®, Tegretol®, Tegretol®-XR, Teril™, Epitol®)
- Phenytoin (Dilantin-125®, Dilantin®)
- Phenobarbital (Solfoton™)
- Rifampin (Rifater®, Rifamate®, Rimactane®, Rifadin®)
- St. John’s wort (Hypericum perforatum)
Ask your doctor if you are not sure if your medicine is one listed above. Know the medicines you take. Keep a list of them to show your doctor and pharmacist when you get a new medicine.
HOW SHOULD I TAKE XARELTO®?
Take XARELTO® exactly as prescribed by your doctor.
Do not change your dose or stop taking XARELTO® unless your doctor tells you to.
- Your doctor will tell you how much XARELTO® to take and when to take it.
- Your doctor may change your dose if needed
If you take XARELTO® for:
o Atrial Fibrillation: Take XARELTO® 1 time a day with your evening meal.
If you miss a dose of XARELTO®, take it as soon as you remember on the same day. Take your next dose at your regularly scheduled time.
o Blood clots in the veins of your legs or lungs:
- Take XARELTO® once or twice a day as prescribed by your doctor.
- Take XARELTO® with food at the same time each day.
- If you miss a dose of XARELTO®:
- and take XARELTO® 2 times a day: Take XARELTO® as soon as you remember on the same day. You may take 2 doses at the same time to make up for the missed dose. Take your next dose at your regularly scheduled time.
- and take XARELTO® 1 time a day: Take XARELTO® as soon as you remember on the same day. Take your next dose at your regularly scheduled time.
- o Hip or knee replacement surgery: Take XARELTO® 1 time a day with or without food. If you miss a dose of XARELTO®, take it as soon as you remember on the same day. Take your next dose at your regularly scheduled time.
- If you have difficulty swallowing the tablet whole, talk to your doctor about other ways to take XARELTO®.
- Your doctor will decide how long you should take XARELTO®. Do not stop taking XARELTO® without talking to your doctor first.
- Your doctor may stop XARELTO® for a short time before any surgery, medical or dental procedure. Your doctor will tell you when to start taking XARELTO® again after your surgery or procedure.
- Do not run out of XARELTO®. Refill your prescription for XARELTO® before you run out. When leaving the hospital following a hip or knee replacement, be sure that you have XARELTO® available to avoid missing any doses.
- If you take too much XARELTO®, go to the nearest hospital emergency room or call your doctor right away.
WHAT ARE THE POSSIBLE SIDE EFFECTS OF XARELTO®
Please see “What is the most important information I should know about XARELTO®?”
Tell your doctor if you have any side effect that bothers you or that does not go away.
Call your doctor for medical advice about side effects. You are also encouraged to report side effects to the FDA: visit http://www.fda.gov/medwatch or call 1-800-FDA-1088. You may also report side effects to Janssen Pharmaceuticals, Inc., at 1-800-JANSSEN (1-800-526-7736).
Please click here for full Prescribing Information, including Boxed Warnings, and Medication Guide.
Trademarks are those of their respective owners.
Janssen and Bayer together are developing rivaroxaban.
For more information about XARELTO®, visit www.xarelto.com.
Note: Content is Not intended as medical advice. Please consult your health care provider regarding your specific medical condition and questions.
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