EINSTEIN CHOICE Studies Low-Dose Rivaroxaban to Reduce VTE Recurrence

March 18, 2017—The American College of Cardiology (ACC) announced that findings from the EINSTEIN CHOICE study demonstrated that a low dose of the oral anticoagulant rivaroxaban in patients at elevated risk for a recurrence of venous thromboembolism (VTE) reduced recurrences by more than threefold compared with aspirin, with no significant increase in bleeding side effects.

The study was presented by Philip S. Wells, MD, during a Late-Breaking Trials session at ACC.17, the American College of Cardiology’s 66th annual scientific session in Washington, DC. The study was simultaneously published online by Jeffrey I. Weitz, MD, et al in The New England Journal of Medicine.

In the ACC announcement, Dr. Wells commented, “We have shown that practitioners can safely prescribe rivaroxaban for patients at risk for a recurrent VTE without being concerned that doing so will increase risk for bleeding side effects.” Dr. Wells is chief of the department of medicine at the University of Ottawa and Ottawa Hospital in Ottawa, Ontario.

Dr. Wells noted that patients who have had a VTE generally are treated with an anticoagulant for 6 to 12 months after the event; however, some patients remain at elevated risk for another blood clot, as well as for a heart attack or stroke, if anticoagulant therapy is stopped. The most common risk factors for VTE are cancer and immobility due to surgery or illness. In addition, some patients develop "unprovoked” VTEs, which occur in the absence of known risk factors.

He explained in the ACC announcement that this study was the first to directly compare the safety and effectiveness of rivaroxaban and aspirin in patients at risk for a recurrent VTE.

The background of the EINSTEIN CHOICE study is that previous studies have suggested that extended treatment with an anticoagulant such as warfarin or rivaroxaban reduced risk for a recurrent VTE, while other studies have shown that aspirin also reduced risk for a recurrent VTE and might present a lower risk for bleeding side effects than extended treatment with an anticoagulant.

As summarized by ACC, the international multicenter EINSTEIN CHOICE study, which was sponsored by Bayer AG, enrolled 3,396 patients who had completed 6 to 12 months of anticoagulant therapy for a VTE. The study patients' average age was 59 years, 55% were men,  77% were Caucasian, 14% were Asian, and 4% were African-American. Patients were randomly assigned to receive 10 mg of rivaroxaban, 20 mg of rivaroxaban, or 100 mg of aspirin once daily for up to 12 months.

The study’s primary efficacy endpoint was recurrence of VTE. Secondary efficacy endpoints were deaths caused by VTE and unexplained deaths for which VTE could not be excluded as a cause. The primary safety endpoint was major bleeding. The secondary safety endpoint was nonmajor bleeding that caused an interruption in treatment, a minor medical intervention, physician visit, or disruption to daily quality of life.

The ACC reported that after a median follow-up of 351 days, 1.2% of patients receiving 10 mg of rivaroxaban and 1.5% of those receiving 20 mg of rivaroxaban had a recurrence of VTE, compared with 4.4% of patients receiving aspirin. The difference was statistically significant for both rivaroxaban groups compared with aspirin. There were no statistically significant differences on the secondary efficacy endpoints.

Major bleeding occurred in 0.4% of those receiving 10 mg of rivaroxaban, 0.5% of those receiving 20 mg of rivaroxaban, and 0.3% of patients receiving aspirin. The differences that were not statistically significant. There were no statistically significant differences on the secondary safety endpoint. 

Dr. Wells explained, “Rivaroxaban had significantly greater efficacy in preventing VTE recurrence without significantly increasing risk for major bleeding. Our findings show that it’s [a safe option] and appears to be highly protective against potentially life-threatening recurrent VTE.” He advised that a limitation of the study is that the results may not be generalizable to other patients at risk for recurrent VTE. For example, study participants were younger than the typical patient with a VTE. The investigators plan to conduct a follow-up study to examine whether low-dose rivaroxaban is equally effective in other patient populations, stated Dr. Wells in the ACC announcement.