For patients hospitalized for medical illness, giving rivaroxaban after discharge does not significantly reduce the risk of venous thromboembolism, investigators reported.
Previous research suggested that the risk of major bleeding from rivaroxaban outweighed its benefits; however, major bleeding was uncommon in the MARINER trial, reported lead author Alex C. Spyropoulos, MD, of Hofstra University in Hempstead, N.Y., and his colleagues.
“Patients who are hospitalized for acute medical illnesses, such as heart failure, respiratory insufficiency, stroke, and infectious or inflammatory diseases, are at increased risk for venous thromboembolism,” they wrote in the New England Journal of Medicine. The results were also presented at the annual congress of the European Society of Cardiology.
Although the increased risk of thromboembolism continues for at least 6 weeks after hospitalization, postdischarge anticoagulants, such as rivaroxaban, are controversial.
“Studies of extended thromboprophylaxis have shown either excess major bleeding or a benefit that is based mainly on reducing the risk of asymptomatic deep-vein thrombosis,” the investigators wrote.
The researchers aimed to clarify the benefits of rivaroxaban after hospitalization while modifying previous study regimens to limit major bleeding risk.
The double-blind MARINER study involved 12,019 patients who were hospitalized for medical illness and had an increased risk of venous thromboembolism. Hospitalization lasted 3-10 consecutive days. Sufficient risk of thromboembolism was defined by a modified International Medical Prevention Registry on Venous Thromboembolism (IMPROVE) score of 4 or higher (range, 0-10), or an IMPROVE score of 2 or 3 with a plasma D-dimer measurement more than double the upper normal limit.
Patients were randomized to receive either 10 mg of rivaroxaban daily (n = 6,007) or placebo (n = 6,012) for 45 days after discharge. Patients with renal impairment had a reduced dose of 7.5 mg rivaroxaban.
A composite of symptomatic or fatal venous thromboembolism was the primary efficacy outcome. Major bleeding was the safety benchmark.
Efficacy was similar in both groups. Symptomatic or fatal venous thromboembolism occurred in 50 patients (0.83%) in the rivaroxaban group, compared with 66 patients (1.10%) in the placebo group (P = .14). These findings suggest that rivaroxaban provides a minor and insignificant benefit.
Although major bleeding was slightly more common in patients receiving rivaroxaban, compared with patients receiving placebo (0.28% vs. 0.15%), the researchers suggested that, in large populations, the marginal benefit of rivaroxaban might outweigh the increased bleeding risk. Still, the authors noted that “the usefulness of extended thromboprophylaxis remains uncertain.”
“Future studies should more accurately identify deaths caused by thrombotic mechanisms and focus on the patients who are at highest risk and who may benefit from anticoagulant prophylaxis,” the researchers wrote.
Funding was provided by Janssen Research and Development. Most of the study authors reported fees or grants from Janssen during the study, and relationships with other companies outside of the submitted work.
SOURCE : Spyropoulos AC et al. N Engl J Med. 2018 Aug 26. doi: 10.1056/NEJMoa1805090.