麻豆传媒

MUNICH -- A 45-day course of rivaroxaban (Xarelto) had no effect in terms of extended thromboprophylaxis for patients leaving the hospital after an acute medical illness, investigators reported from the MARINER trial.

Symptomatic venous thromboembolism (VTE) and death caused by VTE over this period were no less likely when patients had been randomized to take the oral anticoagulant instead of placebo (0.83% vs 1.10%, HR 0.76, 95% CI 0.52-1.09), according to Alex Spyropoulos, MD, of Northwell Hospital at Lenox Hill Hospital in New York City, and colleagues.

At least the odds of major bleeding by day 75 were not a disadvantage for the rivaroxaban group (0.28% vs 0.15%, HR 1.88, 95% CI 0.84-4.23), Spyropoulos told the audience at a late-breaking trial session at the European Society of Cardiology (ESC) annual meeting. The findings were simultaneously published in the .

"In a previous trial involving medically ill patients, treatment with rivaroxaban at a dose of 10 mg once daily started in the hospital and continued for 35 days reduced VTE but increased major bleeding [to 4.1% by day 35]. Therefore, one goal of the current trial was to improve the safety of rivaroxaban in this population," he said.

The 0.28% incidence of major bleeding meant that they achieved that safety goal, the authors said, noting that they did it by reducing the rivaroxaban dose to 7.5 mg in patients with moderate renal impairment, excluding patients at high bleeding risk, and initiating the drug at discharge.

A significant reduction in symptomatic but non-fatal VTE suggested that the study wasn't a total loss for rivaroxaban in extended thromboprophylaxis (0.18% vs 0.42%, HR 0.44, 95% CI 0.22-0.89).

Moreover, the investigators might have seen a treatment effect if the study go out to 60 days, Spyropoulos suggested.

Additionally, although the trial suggested that non-vitamin K antagonist oral anticoagulants should not be prescribed post-discharge to medically ill patients in general, specific subgroups —namely heart failure patients — may still benefit from standard VTE prophylaxis, speculated ESC discussant Malte Kelm, MD, of University Hospital Dusseldorf in Germany.

This would have to be proven with future trials, Kelm cautioned.

MARINER included 12,024 patients ages ≥40 who were considered at increased risk of deep vein thrombosis or pulmonary embolism. To be eligible, they had to score ≥4 on the modified International Medical Prevention Registry on Venous Thromboembolism scale (or 2-3 if they also had a high plasma D-dimer level).

All participants had been hospitalized for 3-10 days because of an acute medical illness such as heart failure, respiratory insufficiency, stroke, and infectious disease.

The trial was conducted in 36 countries. Randomization took place at hospital discharge or the day after. Events were adjudicated by an independent clinical events committee.

Before the ESC presentation, a poll among audience members revealed that low-dose, low-molecular weight heparin upon admission is currently the most common prophylactic strategy for patients at high risk for pulmonary embolism.

The MARINER data left most of the audience saying in another poll that the trial wouldn’t change their practice, or that they didn’t believe the results were conclusive.

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