Recent trial results from the EINSTEIN CHOICE study, published in the New England Journal of Medicine and presented at the American College of Cardiology’s 66th Annual Scientific Session and Expo, revealed important new information about extended anticoagulation treatment that could change how doctors treat venous thromboembolism (VTE).
“The EINSTEIN CHOICE trial focuses on extended therapy for VTE,” explained Dr. Jeffrey Weitz, executive director of the Thrombosis & Atherosclerosis Research Institute and Professor of Medicine and Biochemistry at McMaster University. The goal of the trial was to uncover the best form of extend treatment for VTE by compare different doses of rivaroxaban with aspirin.
“The issue is that many patients with VTE benefit from extended therapy, but the ideal form of extended therapy was uncertain. Attempts to reduce the bleeding liability have included using lower doses of anticoagulants or putting patients on aspirin,” Dr. Weitz continued. “What the EINSTEIN CHOICE study did for the first time is compare these strategies.”
The study was a multicenter, randomized, double-blind, event driven, superiority study. Researchers worked with 3,365 patients who had been diagnosed with venous thromboembolism and had received anticoagulation treatment for six to twelve months after. The trial compared two doses of rivaroxaban (10 mg or 20 mg daily) with 100 mg of aspirin.
“Patients with VTE, who had completed at least six to 12 months of anticoagulation treatment and for whom there was equipoise about the need for continued anticoagulation therapy, were randomized to full dose rivaroxaban (2 mg once daily), prophylaxis dose rivaroxaban (10mg once daily) or to aspirin (100 mg once daily),” said Dr. Weitz.
The results of the study were significant.
“What we showed was that both doses of rivaroxaban were superior to aspirin in the prevention of the recurrence of VTE and were associated with similar rates of bleeding,” Dr. Weitz concluded.
What do the results mean for patients?
EINSTEIN CHOICE is a significant trial that could change the way many doctors and clinicians view extended VTE therapy. It could also change the role they see aspirin playing in VTE treatment.
“I think what this study does is it shows that we have more options for extended treatment. We can use full dose rivaroxaban or prophylaxis rivaroxaban, and we can tailor the dose to the risk profile of the patient,” Dr. Weitz remarked. “Rivaroxaban at those doses is much more effective than aspirin and just as safe. Unless cost is an issue, there’s really little rational in giving aspirin for secondary prevention because once daily rivaroxaban is simple, safe, and more effective.”
“I think that in general with the advent of the DOACs… they’ve led physicians to treat more patients with extended anticoagulation because we have a safe simple approach,” he said, highlighting the growing importance of direct oral anticoagulants (DOACs). “Now with the EINSTEIN CHOICE results, I think it gives you more information and says that you’re better off with an anticoagulant than you are with aspirin, and now it gives you the choice of either the 20mg dose or the 10 mg dose.”
The trial results showed that 60 percent of the patients in the trial were considered to have a provoked VTE. Dr. Weitz pointed out that patients are often divided into provoked and unprovoked VTE, but that even doctors can mislabel these two subdivisions of VTE
The EINSTEIN CHOICE trial showed that both types of VTE patients benefit from extended anticoagulation therapy.
“We show in the EINSTEIN CHOICE publication that regardless of whether patients had provoked or unprovoked VTE, there was a significant reduction in the risk of recurrence with rivaroxaban,” Dr. Weitz explained. “The rates of recurrence weren’t that different in the provoked patients than in the unprovoked patients”
The aspirin arm of the EINSTEIN CHOICE trial presented a challenge for researchers. While it provided valuable data and was a major part of the trial, it caused certain participants to be ruled out.
The use of aspirin led to the exclusion of patients who are on aspirin to treat a cardiovascular disease, as well as patients who are at the highest risk of having a recurrent VTE.
“The problem with having an aspirin in the trial [was that] this led to the exclusion of the highest risk patients because their doctors may have feared them being placed on aspirin,” Dr. Weitz explained. These patients would have been negatively affected by being on the aspirin.
“That’s why I’m hesitant to say that all patients with VTE, who have been treated for 6-12 months…might be eligible for the reduced dose,” he remarked, acknowledging certain gaps that the EINSTEIN CHOICE trial faced. “I think we had under-representation of the highest risk patients.”
The EINSTEIN CHOICE trial may be completed, but its researchers plan on continuing their study through a trial extension. They will be looking to dig deeper into subgroups of provoked and unprovoked VTE and how this affects extended anticoagulation therapy.
“I think the main thing that we discovered was that 60 percent of the patients got defined as having provoked VTE,” Dr. Weitz answered when asked if he was surprised by any of the research findings. “We now have the opportunity to drill down more into that. Stay tuned, we hope to have that out soon.”