Extended rivaroxaban cuts post-discharge VTE, but not mortality, in medically ill patients
Treatment with rivaroxaban for 45 days after hospital discharge reduces symptomatic venous thromboembolism (VTE), but not VTE-related mortality, in medically ill patients, results of the MARINER trial have shown.
In the trial, medically ill patients (mean age, 69.7 years) at increased risk for VTE were assigned at hospital discharge to receive rivaroxaban 10 mg/day (7.5 mg/day for renal insufficiency) (n=6,007) or placebo (n=6,012) for 45 days. The primary efficacy outcome of symptomatic VTE or VTE-related death occurred in 0.83 percent of patients in the rivaroxaban group vs 1.1 percent of patients in the placebo group (hazard ratio [HR], 0.76; 95 percent confidence interval [CI], 0.52 to 1.09; p=0.136). [N Engl J Med 2018, doi: 10.1056/NEJMoa1805090]
“We found no significant between-group difference in the primary efficacy endpoint when results were analyzed by dose stratum and patients’ baseline renal function,” said investigator Professor Alex Spyropoulos of Northwell Health at Lenox Hill Hospital, New York, US, at the European Society of Cardiology (ESC) Congress 2018.
In patients with normal renal function, the primary efficacy outcome occurred in 0.65 percent of those receiving rivaroxaban 10 mg/day vs 0.98 percent of those receiving placebo (p=0.075). In patients with creatinine clearance of 30 to <50 mL/min, the rate of the primary efficacy outcome was 1.64 percent in those receiving rivaroxaban 7.5 mg/day vs 1.64 percent of those receiving placebo (p=0.994).
“The lower dose of rivaroxaban used in study participants with renal impairment might have been insufficient to afford protection from VTE,” Spyropoulos noted.
Exploratory analysis of secondary efficacy outcomes showed no significant reduction in VTE-related mortality with rivaroxaban vs placebo (0.72 percent vs 0.77 percent for placebo; HR, 0.93; 95 percent CI, 0.62 to 1.42; p=0.751). However, patients who received extended thromboprophylaxis with rivaroxaban did have a significant reduction in symptomatic VTE (0.18 percent vs 0.42 percent; HR, 0.44; 95 percent CI, 0.22 to 0.89; p=0.023) as well as a significant reduction in the composite of symptomatic VTE and all-cause mortality (1.3 percent vs 1.78 percent; HR, 0.73; 95 percent CI, 0.54 to 0.97; p=0.033).
Major bleeding, a primary safety outcome of the trial, occurred at low rates in both groups and was not significantly increased with rivaroxaban vs placebo (0.28 percent vs 0.15 percent; HR, 1.88; 95 percent CI, 0.84 to 4.23; p=0.124). However, an increase in non-major clinically relevant bleeding was noted with rivaroxaban vs placebo (1.42 percent vs 0.85 percent; HR, 1.66; 95 percent CI, 1.17 to 2.35; p=0.004).
The trial included patients who had been hospitalized for 3–10 days for heart failure with a left ventricular ejection fraction of ≤45 percent (40.6 percent in rivaroxaban group vs 39.9 percent in placebo group), respiratory insufficiency or exacerbation of chronic obstructive pulmonary disease (26.2 percent vs 26.8 percent), infectious disease (17.5 percent vs 17.4 percent), ischaemic stroke (14.3 percent vs 14.4 percent), or inflammatory disease (1.4 percent vs 1.5 percent).Despite their strategy to enrich the trial with a high-risk population, the investigators noted that the incidence of events remained relatively low. The low event rates, together with the lack of effect on VTE-related mortality, suggest that the usefulness of extended thromboprophylaxis remains uncertain, they noted.