Photo courtesy of CDC
Doctor and patient
MUNICH—Extended thromboprophylaxis with rivaroxaban does not significantly reduce the risk of fatal venous thromboembolism (VTE) in patients hospitalized for medical illness, according to new research.
In the MARINER trial, the combined rate of symptomatic VTE and VTE-related death was similar in patients who received placebo and those who received rivaroxaban for 45 days after hospital discharge.
Rates of VTE-related death were similar between the treatment groups, but the rate of nonfatal VTE was lower with rivaroxaban.
The researchers therefore concluded that some medically ill patients may benefit from extended thromboprophylaxis with rivaroxaban, although more research is needed.
Alex C. Spyropoulos, MD, of Northwell Health at Lenox Hill Hospital in New York, New York, presented these results at ESC Congress 2018.
The research was also published in NEJM. The study was funded by Janssen Research and Development.
The MARINER trial included 12,019 medically ill patients who had an increased risk of VTE and had been hospitalized for 3 to 10 days.
The patients were randomized to receive rivaroxaban (n=6007) at 10 mg daily (7.5 mg in patients with renal impairment) or daily placebo (n=6012) for 45 days after hospital discharge. In all, 11,962 patients (99.5%) received at least one dose of assigned treatment.
Results
The study’s primary endpoint was a composite of symptomatic VTE and VTE-related death. This endpoint was met in 0.83% (n=50) of patients in the rivaroxaban arm and 1.10% (n=66) of patients in the placebo arm (hazard ratio [HR]=0.76; P=0.136).
The incidence of VTE-related death was 0.72% (n=43) in the rivaroxaban arm and 0.77% (n=46) in the placebo arm (HR=0.93, P=0.751).
The incidence of symptomatic VTE was 0.18% (n=11) in the rivaroxaban arm and 0.42% (n=25) in the placebo arm (HR=0.44, P=0.023).
“We were able to reduce instances of non-fatal blood clots and pulmonary embolism by more than half, which shows that the use of direct oral anticoagulants . . . after the hospitalization of medically ill patients could help prevent clots from forming,” Dr. Spyropoulos said.
He and his colleagues also examined an exploratory secondary composite endpoint of symptomatic VTE and all-cause mortality and found that 1.30% (n=78) of patients in the rivaroxaban arm experienced an event, compared to 1.78% (n=107) of patients in the placebo arm (HR=0.73, P=0.033).
The study’s principal safety outcome was major bleeding. It occurred in 0.28% (n=17) of patients in the rivaroxaban arm and 0.15% (n=9) of those in the placebo arm (HR=1.88, P=0.124).
The difference in risk of major bleeding with rivaroxaban compared to placebo was 0.28 percentage points, and the difference in risk of symptomatic VTE with rivaroxaban vs placebo was -0.24 percentage points.
This suggests the number of patients needed to prevent one symptomatic VTE event is 430, and the number needed to cause one major bleed is 856.
Dr. Spyropoulos therefore concluded that thromboprophylaxis, when used in appropriate medically ill patients, might reduce the population health burden of symptomatic VTE with little serious bleeding.
“Our next course of research is to further identify and refine a post-discharge treatment program which would maximize the net clinical benefit across a defined spectrum of medically ill patients,” he said.