Rivaroxaban

The FDA on Thursday will convene an advisory committee to discuss the safety and efficacy of AstraZeneca’s Andexxa, which won accelerated approval in 2018 to reverse the anticoagulation effects of blood thinners that can cause life-threatening bleeding. The Cellular, Tissue, and Gene Therapies Advisory Committee will discuss the results of the confirmatory trial for the treatment. Also known as andexanet, it improved upon the standard of care but also revealed some safety issues and other concerns, FDA said in briefing documents released on Tuesday. The committee isn’t scheduled to vote on a recommendation. “Although andexanet showed superiority of the primary efficacy endpoint over UC [usual care] within the PEP [primary efficacy population], the superior efficacy at 12 hours did not predict longer-term benefit,” FDA said in its document. The FDA wants to hear more from the committee about increased rates of dangerous clotting and clotting-related deaths seen in a trial of Andexxa, compared with a standard of care reversal agent. And it’s looking for more discussion of the clinical meaningfulness of the benefit of Andexxa, and whether the benefit shown in the trial “outweighs the serious risks.” The treatment, a recombinant modified human factor Xa protein, is for patients treated with rivaroxaban or apixaban when rapid reversal of anticoagulation is needed because of life-threatening or uncontrolled bleeding. That could include, for example, when a patient needed urgent surgery because of a medical emergency or accident. Last year, AstraZeneca began plans to shift Andexxa to a full approval from its accelerated approval after halting its confirmatory trial early due to these efficacy findings. But FDA explained how the confirmatory trial, known as ANNEXA-I, revealed “major safety findings” including a “doubling of the rate of thromboses and thrombosis related deaths at Day 30 in the andexanet arm compared with” a standard of care clotting agent known as a prothrombin complex concentrate. Of the 239 patients treated with andexanet, FDA said, 14.6% of patients suffered thrombotic events versus 6.9% in the standard of care arm. While Andexxa demonstrated a statistically significant improvement in hemostasis, or the process to stop bleeding, compared with standard care, the agency also said that the “observed treatment difference between arms appears to be primarily driven by hematoma volume, with more patients in the andexanet arm compared to UC arm experiencing a ≤35% increase from baseline in hematoma volume at 12 hours (74% versus 60%).”

TUESDAY, Nov. 19, 2024 -- People using blood thinners to control their heart rhythm shouldn't expect the medications to head off thinking declines as well, new research suggests. The study, presented Saturday at a meeting of the American Heart Association in Chicago, is the first large trial to investigate whether anti-clotting medication can lower the risk of mental decline, stroke or mini-stroke in adults with atrial fibrillation (A-fib). A-fib is an irregular heartbeat that can lead to serious issues, including heart failure and stroke. It has also been linked to mental decline. "Although numerous observational studies have reported an association between A-fib and cognitive decline, we found that anticoagulation therapy initiated in relatively younger adults with A-fib did not reduce this risk," said study leader Dr. Lena Rivard , an associate professor of medicine at the University of Montreal. "Patients should adhere to standard recommendations for cognitive health, including adopting a healthy lifestyle, engaging in activities that stimulate their brains and maintaining regular physical activity," she added in a meeting news release. For the study, her team investigated the anti-clotting medication rivaroxaban . It's often prescribed to patients over 65 who are at risk for stroke. Those patients include folks who have had a previous stroke, mini-stroke, high blood pressure, diabetes or heart failure. The new study, which included more than 1,200 adults, confirms that the risk of stroke in younger patients with A-fib is small. It also supports current treatment guidelines. Researchers had planned to follow participants, on average, for up to five years. But the study was ended after about 3-1/2 years, because the lack of cognitive benefit from the medication was clear. On average, participants were 53 years of age. They had A-fib but none of the standard risk factors that would require a blood thinner. Half received 15 milligrams (mg) of rivaroxaban daily, the others received a placebo. They had annual tests of thinking skills and were monitored for stroke or transient ischemic attacks (TIAs), also known as mini-strokes. After an average of almost four years, 20% experienced mental decline, stroke or TIAs. Cognitive decline accounted for 91% of this outcome. It was measured on a standard test called the Montreal Cognitive Assessment, and cognitive decline was considered significant if there was a drop of 2 points or more. One in 200 participants had major bleeding and fewer than 1 in 100 (0.8%) had a stroke each year. Outcomes were no different between those taking rivoroxaban and the placebo. "In clinical practice, people younger than age 65 with A-fib tend to be over-treated with anticoagulant therapy, while older people who have indications for anticoagulation are under-treated," Rivard said in a meeting news release. "Our study supports current guidelines by confirming that younger people with A-fib but no other risk factors for stroke have a low rate of stroke, and anticoagulation is not useful in reducing the risk of cognitive decline," she added. Research presented at meetings is considered preliminary until published in a peer-reviewed journal. Whatever your topic of interest, subscribe to our newsletters to get the best of Drugs.com in your inbox.