Edoxaban, an oral anticoagulant, was equally or more effective than warfarin in reducing the risk of stroke and blood clots for patients after heart valve replacement surgery, according to preliminary late-breaking science presented today at the American Heart Association's Scientific Sessions 2024. The meeting, Nov. 16-18, 2024, in Chicago, is a premier global exchange of the latest scientific advancements, research and evidence-based clinical practice updates in cardiovascular science.
Patients who receive a heart valve replacement are well-known to be at a high risk for stroke, blood clots and deep vein thrombosis, especially during the weeks immediately after surgery. Current treatment guidelines recommend anticoagulant therapy with medication to prevent and treat blood clots.
People who receive a mechanical heart valve require lifelong anticoagulant therapy to prevent thrombus (blood clot) formation on the valve. Patients who receive a bioprosthetic (made with human or animal tissue) heart valve typically need anticoagulants for three to six months after surgery.
The standard medication for anticoagulation in these patients is warfarin, which decreases the body's ability to form blood clots by blocking the formation of clotting factors dependent on vitamin K.
Currently, we can use only vitamin K antagonists such as warfarin for patients early after bioprosthetic valve surgery. However, warfarin has a narrow therapeutic range requiring frequent blood testing to monitor clotting activity, and it also interacts with other medications and food, which can be a challenge for patients and the health care professionals treating them."
Chisato Izumi, M.D., Ph.D., lead study author of the National Cerebral and Cardiovascular Center in Suita, Japan
The ENBALV trial evaluated the effectiveness and safety of edoxaban, an oral anticoagulant that was approved by the FDA in 2015 for patients with non-valvular atrial fibrillation, compared to warfarin within three months after bioprosthetic valve surgery. Edoxaban works by blocking factor Xa, a clotting factor that plays a key role in the coagulation (blood clotting) process. Edoxaban is taken in a fixed dose and has a predictable pharmacokinetic profile, which means that its effects are not impacted by diet or other medications.
The randomized, multi-center trial included approximately 400 adults in Japan who had bioprosthetic heart valve replacement surgery at the aortic and/or mitral position. Researchers randomized the participants into two equal groups to receive either edoxaban or warfarin for 12 weeks after surgery.
The analysis found:
- Edoxaban was equally or more effective than warfarin at preventing stroke and blood clots: 0.5% of patients receiving edoxaban had a stroke or systemic embolism, compared to 1.5% of patients receiving warfarin.
- Major bleeding occurred in 4.1% of the edoxaban group and in 1% of the warfarin group. However, no fatal bleeding or intracranial hemorrhage was observed in patients treated with edoxaban, whereas one fatal cerebral hemorrhage occurred in the warfarin group.
- Intracardiac thrombus (a blood clot in the heart) did not occur in any of the patients in the edoxaban group, but did occur in 1% of patients in the warfarin group.
- Patients who received edoxaban did experience higher instances of gastrointestinal bleeding compared to patients who received warfarin (2.1% vs. 0%, respectively).
"Our findings show that edoxaban could help prevent blood clots and stroke as effectively as warfarin, indicating it is a viable post-surgery treatment alternative to consider for patients who have received a bioprosthetic heart valve replacement," Izumi said. "Edoxaban could make life easier for patients recovering from heart valve surgery. Since this medication does not require regular blood tests to monitor anticoagulation activity and can be taken in a fixed dose, without fears of interaction with food or other medications, it reduces the burden on patients and improves their quality of life, especially in those crucial first few months after surgery."
The researchers said future research is needed to understand which patients have the highest risk of bleeding with the use of edoxaban and how to mitigate this risk while still offering effective treatment options in post-surgery treatment and recovery. The effectiveness and safety of other direct oral anticoagulants besides edoxaban also warrants further investigation.
The study had several limitations including that it was open label, meaning all health care professionals and participants knew which medication they were receiving, which may have resulted in bias. In addition, the study did not include patients undergoing transcatheter valve replacements (aortic valve replacement with a man-made valve).
Study details, background and design:
- The study enrolled 410 patients at 24 institutions in Japan who had bioprosthetic valve replacement at the aortic and/or mitral position between May 2022 and January 2024; 389 patients were included in the final analysis.
- Participants were randomized to receive either edoxaban (60 mg or 30 mg taken orally, once daily) or warfarin (administered orally, with dosing adjusted by monitoring the time taken for the patient's blood to clot) for 12 weeks after surgery.
- Patients were ages 41-84 years old, with an average age of 73 years. The edoxaban group was 51% male and 49% female; the warfarin group was 63% male and 37% female.
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