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Rivaroxaban (Xarelto) was not linked with a significantly lower risk of symptomatic venous thromboembolism (VTE) and death due to VTE, versus placebo when given to medical patients for 45 days after hospital discharge, researchers reported.

The primary efficacy outcome -- a composite of symptomatic VTE or death due to VTE -- occurred in 0.83% who were given rivaroxaban and in 1.10% who were given placebo (hazard ratio 0.76, 95% CI 0.52-1.09, P=0.14), according to Alex Spyropoulos, MD, of Northwell Health at Lenox Hill Hospital in New York City, and colleagues.

The prespecified secondary outcome of symptomatic nonfatal VTE occurred in 0.18% of patients on rivaroxaban and 0.42% of patients on placebo (HR 0.44, 95% CI 0.22-0.89), they reported at the European Society of Cardiology annual meeting and simultaneously in the .

The enrolled 12,019 medically ill patients -- 6,007 were assigned to rivaroxaban at once-daily dose of 10 mg (adjusted for renal insufficiency) and 6,012 to placebo for 45 days. The intention-to-treat analysis included 12,019 patients.

Patients were at increased risk for VTE based on a modified International Medical Prevention Registry on Venous Thromboembolism (IMPROVE) of ≥4 or a score of 2 or 3 plus a plasma D-dimer level of more than twice the upper limit of the normal range, the authors noted.

The principal safety outcome of major bleeding occurred in 0.28% of 5,982 patients in the rivaroxaban group and in 0.15% of 5,980 patients in the placebo group (HR 1.88, 95% CI 0.84-4.23).

"The difference in risk (rivaroxaban minus placebo) was 0.13 percentage points (95% CI -0.03 to 0.30)," the authors wrote.

In a subgroup analysis of major bleeding, "there were no significant interactions between the trial regimen and any subgroup variable, with the exception of the duration of the index hospitalization (P=0.02) and in-hospital receipt of thromboprophylaxis (P=0.03)," they added.

Finally, adverse events occurred with similar frequency in the two groups, with 160 patients dying during the 45-day treatment phase, specifically 71 in the rivaroxaban arm and 89 in the placebo arm.

Rivaroxaban may still be worthwhile in selected subgroups, the authors noted, writing that "Optimizing thromboprophylaxis based on appropriate selection of medically ill patients may reduce the population health burden of symptomatic VTE post-discharge at the cost of little serious bleeding. Treatment with rivaroxaban could prevent about 10,000 fatal or non-fatal pulmonary embolic events in medically ill patients. 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."

However, Ileana Pina, MD, MPH, of Albert Einstein College of Medicine in New York City, told 番茄社区app that she was not convinced there was a role for rivaroxaban in this patient population.

"This was a neutral trial," she said. "There is some interest in a subgroup analysis in this trial. But we get burned a lot with subgroup analyses that appear very promising, but when you go and test it [in clinical practice], it is not there. If they are really interested in this subgroup, they need to go and test it prospectively."

Pina, who was not involved in the research, said that the study population does have unmet clinical needs.

"We do worry about patients post-discharge -- I call it the perilous times post-discharge," she said. "Patients are getting back home; they are back on their diets, good or bad; back on their previous medicines...sometimes people are very confused about whether they should take their old medicine or their new medicine. They are likely not to start their cardiac rehab, even though they should. They rest and sit around more and are not as active. So there are people who are very vulnerable to development of venous thromboembolism."

In MARINER, "they were given a very potent drug, but it showed nothing," Pina added. "And it is an expensive drug as well. The only comforting thing was that the bleeding rate was low," she noted. "Even so, gastrointestinal bleeding is deeply disturbing to us and to the patient because you can't always just say 'It's the drug.' You have to work it up and try to find out what is causing the bleeding. That means you have to do endoscopy or even capsule studies because bleeding can be profound."

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