Fatal Bleeding Still Occurring With New Blood Thinners Despite Antidotes: Study

The findings of a new study reveal many bleeding events among users of a new generation of blood thinners, such Pradaxa, Xarelto and Eliquis, still end in death, despite the introduction of “reversal agents” intended to stop their blood thinning effects.

Direct Oral Anticoagulants (DOACs) cause major bleeding in 2% to 3.5% of all patients, according to new data from Spanish researchers. When the drugs were first introduced several years ago, however, there were no medications specifically designed to halt their blood thinning effects, often leaving doctors with no way to prevent patients from bleeding out.

In 2017 and 2018, that changed, first with a reversal agent for Pradaxa, and then with a reversal agent for Xarelto, Eliquis and other Factor Xa inhibitors. However, according to the new study published in the Journal of the American College of Cardiology on June 14, the risk of death from bleeding events still remains high, even for patients given the reversal agents.

Researchers looked at data from 60 studies, involving 4,735 patients who suffered severe bleeding related to the use of Pradaxa, Xarelto, Eliquis and other DOACs. They were given either the reversal agent for Pradaxa or the reversal agent for Xarelto and Eliquis. However, the mortality rate was still high, at just under 18%, and was more than 20% for those who suffered intracranial bleeding, or brain bleeds. The rebleeding rate was 13.2%, with 78% of those rebleeds occurring after the patients were put back on the blood thinners.

Researchers also found a high rate of thromboembolism, potentially fatal blood clots, were associated with AndexXa; the reversal agent for Xarelto and Eliquis.

At issue was the rate of effective hemostasis, the ability for the reversal agents to cancel out the blood thinning effects, which was only 78.5%. The rate was similar regardless of which reversal agent was used, and researchers found that patient risk of death was “markedly and significantly” tied to whether the patients achieved effective hemostasis.

“The risk of death after severe DOAC-related bleeding remains significant despite a high rate of effective hemostasis with reversal agents,” the researchers determined. “Failure to achieve effective hemostasis strongly correlated with a fatal outcome.”

Incidents of unstoppable bleeding have resulted in thousands of reports involving injury or death for patients using the new drugs. About 30,000 Xarelto lawsuits were filed against the drug makers, alleging that users and the medical community were not adequately warned about the risk of problems linked to the drug.

Following a handful of early bellwether trials, which were held before U.S. District Judge Eldon Fallon in the Eastern District of Louisiana to help gauge how juries may respond to certain evidence and testimony that was likely to be repeated throughout the litigation, a global Xarelto settlement was reached in March 2019, resolving nearly all claims.