Randomized trial results show no benefit of treatment with rivaroxaban (Xarelto, Bayer/Janssen) over placebo in reducing a composite endpoint of symptomatic venous thromboembolism (VTE) or death in patients at increased risk for VTE after discharge from a medical hospitalization.

The primary safety outcome, major bleeding, including was low and not significantly increased with treatment, the researchers said.

Results of the Medically Ill Patient Assessment of Rivaroxaban Versus Placebo in Reducing Post-Discharge Venous Thrombo-Embolism Risk (MARINER) trial were presented here at the European Society of Cardiology Congress 2018, to coincide with their publication online in the New England Journal of Medicine.

"In conclusion, our trial did not show a significant benefit of this rivaroxaban regimen started at hospital discharge with regard to the composite outcome of fatal or symptomatic venous thromboembolism in medically ill patients," said the researchers, with lead author Alex C.  Spyropoulos, MD, the Donald and Barbara Zucker School of Medicine.  

However, they add, given the relatively low incidence of events despite their strategy to enrich the trial with a high-risk population, and a lack of effect seen on VTE-related death, "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 may benefit from anticoagulant prophylaxis," they said.

"What this means from a population and other points of view, is that we now can optimize thromboprophylaxis in appropriately selected medically ill patients, and we may reduce by half or more the incidence of symptomatic venous thrombosis at the cost of little to no serious bleeding," he said.

"When we look at modeling estimations of 6 million at-risk patients that would likely qualify for MARINER inclusionary criteria, we could prevent annually up to about 10,000 fatal or nonfatal pulmonary embolic events in these patient populations annually at the cost of one-tenth that number of life-threatening or fatal bleeds."

Professor Stephan Achenbach, MD, from the University of Erlangen, Germany, chairperson of the ESC Congress Programme Committee and ESC president-elect, who co-moderated the session at which MARINER was presented, said these results "will be an aid to decision making for the discharging physician to make decisions, probably not in the way that would change guidelines that would be my current estimate."

Major bleeding, the primary safety endpoint, was defined as overt bleeding associated with a decrease in the hemoglobin level of 2 g/dL or more, bleeding that required transfusion of 2 or more units of packed red cells or whole blood, bleeding that occurred at a critical site or fatal bleeding.

MARINER: Primary Safety Endpoint

"These differences in risk suggest that the number of patients needed to treat to prevent one symptomatic venous thromboembolism event is 430, whereas the number needed to cause one major bleed is 856," they noted.

"Thus, although the benefit-risk decision for the individual patient is finely tuned, the implementation of extended thromboprophylaxis with appropriate selection of medically ill patients may reduce the health burden of nonfatal venous thromboembolism in this population," the researchers said.