An analysis of the MARINER trial is diving deeper into the impact of post-discharge prophylaxis with rivaroxaban in patients with more severe renal impairment.
Gary Raskob, PhD
Results of an exploratory analysis of the phase 3 MARINER study indicates post-discharge prophylaxis with rivaroxaban (Xarelto) could reduce the risk of both fatal and major thromboembolic events in medically ill patients.
Findings from the analysis, which only included data on patients with a baseline creatinine clearance level (CrCl) of 50 ml/min or greater, suggests 10 mg rivaroxaban is superior to placebo for the prevention of a composite of symptomatic venous thromboembolism (VTE), myocardial infarction (MI), nonhemorrhagic stroke, and cardiovascular (CV) death in medically ill patients.
While the original MARINER trial established the safety and efficacy profile of post-discharge rivaroxaban 7.5 and 10 mg for prevention of symptomatic VTE in high-risk medical ill patients, a team of investigators led by Gary Raskob, PhD, dean of Hudson College of Public Health at The University of Oklahoma Health Sciences Center, sought to investigate the effects of 10 mg rivaroxaban in patients with more severe renal impairment. Unlike the original trial, the primary endpoint of this exploratory analysis was a composite of symptomatic VTE, MI, nonhemorrhagic stroke, and CV death.
Raskob and colleagues also assessed major bleeding, as defined by the International Society on Thrombosis and Haemostasis bleeding criteria, as the primary safety outcome of their analysis.
Using a baseline CrCl level of 50 ml/min or greater as the primary inclusion criteria, investigators identified cohorts of 4,909 patients assigned to rivaroxaban and 4,913 patients assigned to placebo for inclusion in their analysis. The entire study population had a mean age of 67.8 years, 55.5% were men, and 96.5% were white—investigators pointed out baseline characteristics were well-balanced between the 2 arms.
Upon analysis, investigators found the composite endpoint occurred in 1.28% of patients receiving rivaroxaban and in 1.77% of those randomized to placebo (HR, 0.72; 95% CI, 0.52-1.00; P=.049). Additionally, incidence of all the components included in the composite endpoint, with the exception of MI, tended to favor rivaroxaban.
Investigators also pointed out symptomatic lower-extremity deep vein thrombosis (HR, 0.20; 95% CI, 0.04-0.91) and symptomatic nonfatal pulmonary embolism (HR, 0.36; 95% CI, 0.12-1.14) showed greater relative risk reduction with rivaroxaban.
In regard to the safety of rivaroxaban versus placebo, the primary safety endpoint of major bleeding occurred in 0.27% (n=13) of patients receiving rivaroxaban and 0.18% (n=9) patients in placebo group (HR, 1.44; 95% CI, 0.62-3.37; P=.398).
In an editorial comment published in JACC, Samuel Goldhaber, MD, director of the Thrombosis Research Group at Brigham and Women’s Hospital, noted the findings from MARINER and trials such as the betrixaban substudy APEX may be impressive but implementation will be an arduous process.
“The findings with rivaroxaban and betrixaban suggest that we should abandon a silo approach for the prevention of venous or arterial thrombosis and promote a holistic strategy to vascular disease,” Goldhaber wrote. “Implementation of the lessons from APEX and MARINER will be an uphill journey. The American Society of Hematology guidelines recommend against the use of extended-duration anticoagulant prophylaxis after hospital discharge.”
This study, “Post-Discharge Prophylaxis With Rivaroxaban Reduces Fatal and Major Thromboembolic Events in Medically Ill Patients,” was published in the Journal of the American College of Cardiology.