Apixaban Shows Lower Rate of Bleeding in Large French Real-World Data Study

Real-world data released earlier today in Paris, France, show that the oral anticoagulant apixaban, sold as Eliquis, was associated with lower rates of major bleeding than its competitors in the class, while delivering comparable protection against strokes and blood clotting events in patients with nonvalvular atrial fibrillation (NVAF).

Data from the study, called NAXOS, (EvaluatioN of ApiXaban in strOke and Systemic embolism prevention in patients with nonvalvular atrial fibrillation in the real-life setting in France), also show that apixaban plus aspirin was linked with lower rates of major bleeding, stroke, and systemic thromboembolic events than a vitamin K antagonist (VKA), according to a statement.

Results from NAXOS were presented in a late-breaking session September 1, 2019, at the European Society of Cardiology 2019 Congress. The study examined records from more than 320,000 patients in France age 18 or older who started taking an anticoagulant for NVAF between 2014 and 2016.

“The large-scale NAXOS retrospective observational analysis is significant because it included nearly the entire French population with NVAF and is the first nationwide analysis that has evaluated the effectiveness and safety of all available OACs in France,” Philippe Gabriel Steg, MD, FESC, FACC, head of the Cardiology Department at Hôpital Bichat, Assistance Publique-Hôpitaux de Paris and a professor at Université de Paris, said in a statement. “Being able to analyze data from routine clinical practice from a large patient population may help characterize the effectiveness and safety of available anticoagulants.”

Specifically, the data showed:

• Apixaban was associated with a lower rate of major bleeding than a VKA, with a hazard ratio (HR) of 0.49, 95% CI: 0.46-0.52. By comparison, the oral anticoagulant rivaroxaban had an HR of 0.63, 95% CI: 0.58-67; and dabigatran had an HR of 0.85, 95% CI: 0.76-0.95.
• Apixaban was associated with reduced rates of stroke and systemic thromboembolic events compared with VKA, with an HR of 0.67, 95% CI: 0.62-0.72; results for rivaroxaban were similar, with an HR of 0.97, 95% CI: 0.89-1.05), as were results for dabigatran, HR 0.92, 95% CI: 0.81-1.06.
• Apixaban was also associated with lower rates of all-cause mortality relative to a VKA, results were comparable for rivaroxaban and dabigtran.

Real-world evidence is becoming increasingly important to both health plans and regulators to help fill in knowledge gaps, especially for groups of patients who might be less likely to take part in randomized clinical trials. FDA released a framework last year to guide development of criteria for future use of real-world evidence in the regulatory process.

When asked by The American Journal of Managed Care® if there were any noteworthy subgroup results from NAXOS, Danny Wiederkehr, MPH, Global HEOR Team Lead at Pfizer speaking on behalf of the Pfizer/BMS Alliance, which funded the study, noted that a substantial share of the study population was over 80 years of age.

Wiederkehr said that on average, apixaban patients were slightly older (74.7 years) than those taking rivaroxaban (72.0) and dabigatran (72.7) and younger than those taking VKA (78.5 years). Of the apixaban group, 38.5% were over age 80, compared with 29.6% for rivaroxaban, 32.1% for dabigatran, and 54.5% for VKA. Many of these patients have comorbidities that would keep them out of clinical trials, he said.

“Those older, frailer patients aren’t represented in randomized clinical trials, yet are often the types of patients that physicians see in their everyday medical practices,” Wiederker noted in response to an email question. “As such, data generated from real-world studies like NAXOS can play an important role in their treatment decisions.”

Specifically, Wiederker noted that the study population included a substantial share of patients with coronary artery disease (8.5% for apixaban), history of cancer (14% for apixaban), diabetes (15.6% for apixaban), and prior stroke (9.9% for apixaban). The overall population was at high risk of stroke, and three-quarters had been hospitalized in the previous 2 years.

More subgroup analyses are planned to understand apixaban’s benefits in special populations. “These data add to the growing real-world evidence supporting the clinical benefits of Eliquis and are complimentary to the robust clinical trial data, and which we share with regulators and payors around the world,” he said.

Data from NAXOS are under review for publication in a peer-reviewed journal.

Reference

Steg PG. Apixaban in the prevention of stroke and systemic embolism in patients with atrial fibrillation in real-life setting in France SNIIRAM study. Presented at the European STudy of Cardiology 2019 Congress, September 1, 2019; Abstract 1362.