For people at a high risk of developing blood clots, a prescription for a type of drug called an anticoagulant is vital. But with a particular type of anticoagulant called Factor Xa inhibitors, excessive bleeding is also a risk. Scientists from McMaster University in Canada now introduce andexanet, an experimental drug that, if approved by the FDA, could be the first drug available to treat excessive bleeding for Factor Xa inhibitor patients.
Experts estimate that almost three million people in the United States currently take Factor Xa inhibitors, often older people who are at high risk for stroke and venous thrombosis due to heart failure or other problems. Anticoagulants like Factor Xa inhibitors reduce the body’s ability to form a blood clot, which is good for preventing stroke but bad in cases of uncontrolled bleeding. Andexanet’s role would come into play when patients taking Factor Xa inhibitors experience major bleeding, as the drug can directly counter the effects of the anticoagulant.
About 84,000 people taking Factor Xa inhibitors are hospitalized for major bleeding each year, often due to brain bleeding, a fall, or gastrointestinal bleeding. A quarter of all people taking Factor Xa inhibitors die when bleeding in the brain occurs. Andexanet could be the reversal agent responsible for preventing those deaths.
"Factor Xa inhibitors are already widely used because of their excellent efficacy and safety profile. However, some physicians and patients may choose to use other anticoagulant drugs because they have a reversal agent rather than using one of the Factor Xa inhibitors,” explained lead author Stuart Connolly, MD. “Having a safe and effective reversal agent available will benefit patients with acute bleeding."
Andexanet works by allowing Factor Xa, a blood coagulation factor, do its job: clot the blood. In preliminary studies with healthy patients, researchers showed that andexanet successfully reversed the anti-clotting effect of Factor Xa inhibitors, with no significant negative side effects.
Now researchers are working on a clinical trial called AMNEXA-4, recruiting patients having trouble with major bleeding as a result of taking Factor Xa inhibitors. Researchers are testing the drug for both safety and effectiveness, and so far the drug appears to be working well.
"This study is only focused on patients who are acutely bleeding, but there is also great interest in using a drug like andexanet for patients who come into a medical center on a Factor Xa inhibitor and require urgent surgery," Connolly said. "We hope to study that patient population in the future."