FDA Approves New 10 mg Dosing for Xarelto (rivaroxaban) to Reduce the Continued Risk of Venous Thromboembolism (VTE)

In continuation of my update on rivaroxaban

Janssen Pharmaceuticals, Inc. announced  the U.S. Food and Drug Administration (FDA) approved the 10 mg once-daily dose of Xarelto (rivaroxaban) for reducing the continued risk for recurrent venous thromboembolism (VTE) after completing at least six months of initial anticoagulation therapy. This approval follows a FDA Priority Review and is based on data from EINSTEIN CHOICE, the only clinical study to find that a Factor Xa inhibitor, specifically Xarelto, demonstrates superior efficacy in reducing the continued risk of recurrent VTE and with major bleeding rates similar to aspirin.

VTE includes deep vein thrombosis (DVT), a blood clot in a deep vein (often the legs), and pulmonary embolism (PE), a clot that travels to the lung. It is the third most common cause of cardiovascular death worldwide, after heart attack and stroke.

"We believe the availability of the 10 mg Xarelto dose will change clinical practice and the management of VTE recurrence," said Paul Burton, MD, PhD, FACC, Vice President, Medical Affairs, Janssen. "The landmark EINSTEIN program results yet again demonstrate Xarelto is a safe and highly effective option, not only for the initial treatment of a VTE, but also for the continued prevention of a recurrent event."

With this approval, the Xarelto prescribing information provides instructions for physicians to begin treatment with Xarelto 15 mg, dosed twice daily, for the first 21 days after a VTE occurrence. On day 22 through at least day 180, the daily dose decreases to Xarelto 20 mg once daily. After at least 180 days (6 months), physicians can prescribe Xarelto 10 mg once daily in patients at continued risk for DVT and/or PE.

"If anticoagulation therapy is stopped, up to 20 percent of patients will have a recurrent VTE within three years. To prevent this, physicians have long debated how best to extend anticoagulant use beyond the initial treatment window," said Jeffrey Weitz, MD, FRCP(C), FACP, Professor, Departments of Medicine and Biochemistry and Biomedical Sciences, McMaster University, and Executive Director, Thrombosis & Atherosclerosis Research Institute. "The FDA’s approval of the 10 mg dose of Xarelto for preventing recurrent VTE, along with clinical evidence confirming the superiority of Xarelto over aspirin for extended VTE prevention, means we can finally put this debate to rest."

The FDA’s approval of the Xarelto 10 mg once-daily dose was based on the EINSTEIN CHOICE study results. The EINSTEIN CHOICE study evaluated patients with VTE who were already treated with six to 12 months of initial anticoagulation therapy and then received Xarelto 10 mg once daily, Xarelto 20 mg once daily or aspirin 100 mg once daily for up to an additional 12 months of treatment. Patients taking either Xarelto dose had significantly fewer recurrent VTE compared to those taking aspirin. Specifically, Xarelto 10 mg reduced the risk of recurrent VTE by 74 percent and Xarelto 20 mg by 66 percent. All three treatment groups had low rates of major bleeding (0.4 percent with Xarelto 10 mg, 0.5 percent with Xarelto 20 mg, 0.3 percent with aspirin).

In September 2017, Janssen’s development partner Bayer announced the Committee for Medicinal Products for Human Use of the European Medicines Agency granted a positive opinion to update the Xarelto label to include the 10 mg once-daily dose in the European Union; the European Commission granted approval on October 19, 2017.

FDA Approves New 10 mg Dosing for Xarelto (rivaroxaban) to Reduce the Continued Risk of Venous Thromboembolism (VTE)

XARELTO reduces rates of major bleeding, recurrent blood clots in people with deep vein thrombosis

In continuation of my update on rivaroxaban

Janssen Pharmaceuticals, Inc. (Janssen) and its development partner, Bayer HealthCare, today announced the results from their real-world study XALIA showing that, in people with deep vein thrombosis (DVT), the rates of major bleeding and recurrent blood clots for XARELTO® (rivaroxaban) in routine clinical practice were generally consistent with those observed in Phase 3 research. Patients taking XARELTO® also had shorter length of hospital stays than those given standard anticoagulation. The prospective study was presented at the 2015 American Society of Hematology (ASH) Annual Meeting and simultaneously published in Lancet Hematology.

"On average, every 37 seconds someone in the Western world dies from a venous blood clot, so it is important we understand the effectiveness and safety of available treatment options for these potentially life-threatening blood clots," said XALIA principal investigator Professor Alexander G. G. Turpie, McMaster University and Hamilton Health Sciences, Hamilton, Ontario, Canada. "The real-world insights from XALIA confirm the positive benefit-risk profile of rivaroxaban for the treatment of deep vein thrombosis that was observed in the Phase 3 EINSTEIN-DVT study, signalling that the medicine is performing as expected in patients that physicians typically see in everyday clinical practice."

XALIA – which included approximately 5,000 patients from 21 countries – evaluated the safety and effectiveness of XARELTO®, taken once daily, for the treatment of DVT in routine clinical practice as compared to standard anticoagulation. The primary outcome was the incidence of adverse events (major bleeding, recurrent blood clots and all-cause mortality). Healthcare resource utilization, including length of stay, also was evaluated. A propensity score analysis was completed to address differences in baseline characteristics and help correct any selection bias. Methodological and other differences between the studies limit the ability to directly compare results of XALIA to the pivotal Phase 3 EINSTEIN-DVT study, which was used by regulatory authorities worldwide to approve XARELTO®.

XARELTO reduces rates of major bleeding, recurrent blood clots in people with deep vein thrombosis

Two anticlotting medicines better at reducing bleeding risk than triple therapy

A major international study has found that the combination of two drugs - rivaroxaban and aspirin -- is superior to aspirin alone in preventing further heart complications in people with vascular disease.

The study of 27,400 people with stable coronary or peripheral artery disease from 33 countries worldwide will be published today, and results show that the combination of 2.5 mg of rivaroxaban twice daily plus 100 mg of aspirin once daily was significantly better than only aspirin or only rivaroxaban in preventing heart attacks, strokes, and death. Rivaroxaban, often known by the brand name Xarelto, is an anticoagulant, aspirin is an antiplatelet drug, and both are blood thinners.

  rivaroxaban   Aspirin

The results will be presented today at the Congress of the European Society of Cardiology (ESC) in Barcelona, Spain, and the overall results will be published in the New England Journal of Medicine.

The study, called COMPASS, is led by the Population Health Research Institute (PHRI) of McMaster University and Hamilton Health Sciences (HHS) in Hamilton, Canada. The study is funded by Bayer AG.

The findings are significant because there are about 300 million people around the world living with cardiovascular disease, and every year as many as five to 10 per cent have a stroke or heart attack. Although aspirin reduces the risk of major cardiovascular events by 19 per cent, a more effective antithrombotic strategy could have major benefits for the large population of patients with stable cardiovascular disease.

The clear result of this clinical study - that the combination reduced strokes, heart attacks and cardiovascular death by practically 25 per cent compared to either drug alone in both patients with stable coronary or peripheral artery disease - caused the clinical trial to be stopped early, after 23 months, in February 2017.

The researchers report that the drug combination does increase the chance of a major bleeding. These bleeds were mainly gastroenterological, and not in critical organs such as the brain nor fatal.

Co-principal investigator Dr. John Eikelboom and his team compared rivaroxaban at doses of 2.5 mg twice-daily combined with 100 mg of aspirin once-daily to rivaroxaban 5 mg twice-daily or to aspirin 100 mg once-daily. In the randomized clinical trial, patients were seen at one and six months, and then every six months.

They found the drug combination reduces cardiovascular outcomes, increases bleeding and improves survival in stable coronary or peripheral artery disease.

"Efforts to improve aspirin have focused primarily on combining aspirin with another antiplatelet drug or replacing aspirin with another antiplatelet drug, but this has had only limited success," said Eikelboom. He is a principal investigator of the PHRI, an associate professor of medicine at McMaster and a hematologist at HHS.

Oral drug reduces venous thromboembolism recurrence among cancer patients

In continuation of my update on  rivaroxaban

Research from the University of Warwick indicates that taking a tablet a day can help treat cancer patients of a potentially deadly condition.

People with cancer have an increased risk of developing blood clots, with roughly one in five experiencing venous thromboembolism (VTE) - either deep vein thrombosis (DVT) or pulmonary embolism (PE). Blood clots in the deep veins of the leg may travel to the lungs causing a pulmonary embolism. These two conditions are referred to as VTE - a dangerous and potentially deadly medical condition of which there are 10 million cases worldwide.

Current international guidelines recommend cancer patients are injected with an anticoagulant (a low molecular weight heparin) to treat and prevent recurrence of VTE. However, new results from a large pilot trial run at the University's Warwick Medical School called 'select-d' suggest that a daily tablet could be a beneficial alternative for treating VTE in selected patients.

Research led by Professor Annie Young of Warwick Medical School found that prescribing the oral drug rivaroxaban (Xarelto) significantly reduced venous thromboembolism recurrence among patients with cancer and VTE. She said: "Clinicians were already adopting the oral drug into practice for non-cancer patients and now they have data from this study to indicate that this form of treatment is an alternative option for many cancer patients who have a clot."

 

Although there are many causes and risk factors for VTE, cancer patients are particularly at risk due to a combination of factors such as immobility (if in bed poorly), pancreatic and gastric tumours, and chemotherapy. Because VTE can be life-threatening, blood thinners are used to shrink existing clots and prevent others from forming.

The 'select-d' trial enrolled 406 patients who had cancer and VTE; most (69 percent) were receiving cancer treatment (typically chemotherapy) at the time of their VTE. Half were randomly assigned to receive low-molecular-weight heparin (dalteparin) and half were given the oral drug rivaroxaban. After six months of treatment, the VTE recurrence rate was four percent among those taking the tablet and 11 percent in those receiving dalteparin.

The results for secondary outcomes were mixed. In patients receiving rivaroxaban, there were around the same percentage of major bleeding events (6%) as those receiving dalteparin (4%) but a marked and significant increase in clinically relevant non-major bleeds (13%) with rivaroxaban compared to those having low molecular weight heparin (4%). The reason for increased bleeding is not known, it may be because rivaroxaban is more 'potent'.

Professor Young added: "We now need to be sitting down with each one of our cancer patients with VTE, discussing their preference alongside looking at all their clinical details including whether the cancer lesion is still there, what other medications are being taken and what other conditions the patient has so that we can choose the optimal VTE treatment for each patient."

Positive Results from Chronic Study of Rivaroxaban (anticoagulant drug)...

Rivaroxaban, is an oral anticoagulant invented and manufactured by Bayer; in a number of countries it is marketed as Xarelto. If approved by the United States FDA, it will be marketed by Ortho-McNeil Pharmaceutical. It is the first available orally active direct inhibitor of coagulation Factor Xa. Rivaroxaban is well absorbed from the gut and maximum inhibition of factor Xa occurs three hours after a dose. The effects lasts 8–12 hours, but factor Xa activity does not return to normal within 24 hours so once-daily dosing is possible.

Rivaroxaban is undergoing review by the FDA, On March 19, 2009, an advisory panel recommended FDA approval of rivaroxaban 10 mg once daily for use in patients undergoing hip or knee replacement surgery. The advisory panel concluded that the record trials demonstrate that rivaroxaban is non-inferior and possibly superior to subcutaneous enoxaparin 40 mg once daily. However, they also found an increased risk of bleeding with rivaroxaban and did not address the question of long-term (i.e. > 35 days) use. The advisory panel noted that 1 participant out of 6183 randomized to rivaroxaban died of liver toxicity.....

Source :http://abstracts.hematologylibrary.org/cgi/content/abstract/112/11/436?maxtoshow=&HITS=50&hits=50&RESULTFORMAT=&searchid=1&FIRSTINDEX=0&displaysectionid=Oral+Session&fdate=1/1/2008&tdate=12/31/2008&resourcetype=HWCIT

New oral blood thinners can decrease stroke risk in atrial fibrillation patients without frequent monitoring

In continuation of my update on dabigatran (Pradaxa), rivaroxaban (Xarelto), apixaban (Eliquis) and edoxaban (Savaysa).

A new generation of blood thinners can reduce the risk of stroke in patients with atrial fibrillation, without requiring frequent monitoring and dietary restrictions.

But special attention must be given to the patient's age, kidney function and other factors before prescribing the new medications, according to a review article by neurologists at Loyola Medicine and Loyola University Chicago Stritch School of Medicine.

The report by Rochelle Sweis, DO and José Biller, MD, is published in the journal Current Treatment Options in Cardiovascular Medicine.

Atrial fibrillation (AFib) is the most common type of irregular heartbeat, and the prevalence is increasing as the population ages. In AFib, electrical signals that regulate the heartbeat become erratic. Instead of beating regularly, the upper chambers of the heart quiver and blood doesn't flow well. Blood clots can form, migrate to the brain and cause strokes. AFib is associated with a fivefold increase in the risk of stroke.

Blood thinning medications decrease the stroke risk by approximately 70 percent. For 60 years physicians have prescribed warfarin (Coumadin) and other blood thinners known as vitamin K antagonists. These medications have been proven to be effective in reducing the risk of blood clots and strokes. But they require continual monitoring and dose adjustments to ensure the drugs thin the blood enough to prevent clots, but not enough to increase the risk of major bleeding. Patients also must restrict their consumption of foods rich in vitamin K, such as spinach, Brussels sprouts, kale, parsley and green tea.

 

Warfarin

The new blood thinners include dabigatran (Pradaxa), rivaroxaban (Xarelto), apixaban (Eliquis) and edoxaban (Savaysa). In the right patient population, the new drugs are a safe and effective option for treating atrial fibrillation, Drs. Sweis and Biller write.

Dabigatran         Rivaroxaban (BAY 59-7939)

Apixaban Edoxaban

New oral blood thinners can decrease stroke risk in atrial fibrillation patients without frequent monitoring: A new generation of blood thinners can reduce the risk of stroke in patients with atrial fibrillation, without requiring frequent monitoring and dietary restrictions.

FDA Approves Xarelto (rivaroxaban) to Prevent Deep Vein Thrombosis

We  know that, Rivaroxaban (structure below BAY 59-7939) is an oral anticoagulant invented and manufactured by Bayer; in a number of countries it is marketed as Xarelto. In the United States, it is marketed by Janssen Pharmaceuticals. It is the first available orally active direct factor Xa inhibitor. Rivaroxaban is well absorbed from the gut and maximum inhibition of factor Xa occurs four hours after a dose. The effects lasts 8–12 hours, but factor Xa activity does not return to normal within 24 hours so once-daily dosing is possible....

Now FDA Approves Xarelto (rivaroxaban) to Prevent Deep Vein Thrombosis in Patients Undergoing Knee or Hip Replacement Surgery....

More....

New Anti-Clotting Drug May Cut Brain Bleeding Risk: Study

In continuation of my update on rivaroxaban (Xarelto)

In a new study, researchers led by Dr. Graeme Hankey, a neurologist at the Royal Perth Hospital and University of Western Australia, followed more than 14,000 people who took anti-clotting drugs for a median of two years. Of those patients, 136 had bleeding in the brain.

People who took a new anticoagulant called rivaroxaban (Xarelto) and suffered from the most common type of atrial fibrillation and didn't have heart valve damage were about one-third less likely to experience bleeding in the brain than those who took warfarin, the investigators found...

More...

Aspirin as Good a Clot Buster as Pricey Drugs After Joint Replacement

Good old aspirin is just as effective as newer, expensive drugs at preventing blood clots after hip or knee replacement, a new clinical trial suggests.

Researchers said the findings could change some doctors' prescribing habits.

After knee or hip replacement surgery, there's a risk of blood clots in the legs or lungs. So it's routine for patients to take clot-preventing drugs for some time afterward.

Right now, some doctors choose powerful anti-clotting drugs like dabigatran (Pradaxa) and rivaroxaban(Xarelto), said Dr. David Anderson, the lead researcher on the new trial.

But it hasn't been clear whether those expensive prescription drugs are any better than cheap, readily available aspirin, explained Anderson, of Dalhousie University, in Halifax, Canada.

Based on the new findings, they're not.

Few patients in the study developed a blood clot after surgery, and those on aspirin fared just as well as those on rivaroxaban.

The caveat, Anderson said, was that all study patients received rivaroxaban for the first five days after surgery. After that, they either continued on the drug or switched to aspirin for another nine to 30 days.

"From this study, we have no evidence to support starting aspirin on day one," Anderson said.

But after day five, he added, "it's very reasonable to consider switching to aspirin."

Over the past decade, surgeons have already been turning away from powerful anticoagulants toward aspirin and non-drug options for thwarting clots, said Dr. Alejandro Gonzalez Della Valle.

Gonzalez Della Valle specializes in hip and knee surgery at the Hospital for Special Surgery in New York City.

These days, he said, patients have a generally low risk of blood clots after hip or knee replacement for a number of reasons. Those include shorter surgical times, and the use of regional anesthesia instead of general.

Clots can also be prevented by improving blood flow in patients' legs right after surgery. So getting patients on their feet and moving early on is key, Gonzalez Della Valle explained. Similarly, pneumatic compression devices can be used to encourage blood flow in the lower limbs while patients are in their hospital beds.

Dr. Kevin Bozic, a spokesperson for the American Academy of Orthopaedic Surgeons (AAOS), said that the AAOS guidelines already state that no one drug is better than another for preventing clots.

"This study reinforces that," Bozic said.

He agreed that most surgeons have been turning to aspirin in the past 10 years because recovery times are shorter and people leave the hospital much sooner. Most people can have just aspirin, but some at high risk of blood clots -- those with a history of clots, people who are very obese -- might need an anticoagulant, Bozic added.

"The strategy for preventing clots should include medication and early mobilization," he stressed.

Ref:http://www.nejm.org/doi/full/10.1056/NEJMoa1712746

Aspirin as Good a Clot Buster as Pricey Drugs After Joint Replacement - Drugs.com MedNews

Study Pits New Blood Thinner Against Warfarin For Irregular Heartbeat

A new drug, Rivaroxaban, (see structure) that lowers stroke risk among people with an irregular heartbeat may give the old standby, warfarin, some competition, a new study shows.

 We know that, Rivaroxaban (BAY 59-7939) is an oral anticoagulant invented and manufactured by Bayer; in a number of countries it is marketed as Xarelto. In the United States, it is marketed by Janssen Pharmaceutica. It is the first available orally active direct factor Xa inhibitor. Rivaroxaban is well absorbed from the gut and maximum inhibition of factor Xa occurs four hours after a dose. The effects lasts 8–12 hours, but factor Xa activity does not return to normal within 24 hours so once-daily dosing is possible. Now the  new trial pitted the newer drug, rivaroxaban, against warfarin in more than 14,000 patients who were randomly assigned either warfarin or rivaroxaban. Neither the patients nor the doctors knew who was taking which drug. As per the claim by the resarchers, new agent proved to be as effective as warfarin at reducing the risk of ischemic stroke -- the most common kind of stroke,  but it did not need to be monitored as closely as warfarin since it is given as a one-size-fits-all dose....

"a reasonable alternative to warfarin, with less intracranial or fatal bleeding." claims the lead researcher, Dr. Manesh R. Patel...

Ref : http://www.newsroom.heart.org/index.php?s=43&item=1191

Janssen receives FDA approval for Xarelto to prevent stroke in people with AF

In continuation of my up date on rivaroxaban.....

Janssen receives FDA approval for Xarelto to prevent stroke in people with AF: The U.S. Food and Drug Administration today approved the anti-clotting drug Xarelto (rivaroxaban) to reduce the risk of stroke in people who have abnormal heart rhythm.

Phase III EINSTEIN trial program: XARELTO reduces risk of DVT and PE

In continuation of my update on Rivaroxaban

The EINSTEIN-PE study was an open-label, randomized, non-inferiority trial. The trial compared oral rivaroxaban – 15 mg twice daily for three weeks, followed by 20 mg once daily – with the current standard of care (enoxaparin followed by a Vitamin K Antagonist [VKA]) in subjects with acute symptomatic PE with or without symptomatic DVT. Patients received treatment for six or 12 months. EINSTEIN-PE enrolled 4,833 participants and is the largest study ever conducted in the acute treatment of PE. 

Read more...

Phase III EINSTEIN trial program: XARELTO reduces risk of DVT and PE

New Blood Thinner May Lower Chances of Clots in High-Risk Heart Patients: FDA

In continuation of my update on Rivaroxaban

New Blood Thinner May Lower Chances of Clots in High-Risk Heart Patients: FDA:  The new blood thinner Xarelto appears to lower the chances of potentially fatal blood clots in high-risk heart patients, a U.S. Food and Drug Administration review has found.