Rivaroxaban for Thromboprophylaxis after Hospitalization for Medical Illness (MARINER)

Trial References

Spyropoulos AC, Ageno W, Albers GW, et al.; MARINER Investigators. Rivaroxaban for Thromboprophylaxis after Hospitalization for Medical Illness. N Engl J Med. 2018 Aug 26. doi: 10.1056/NEJMoa1805090.

Abstract | Full Text

Expert Comment

Pablo del Castillo Vazquez,  Antoni Martínez-Rubio: Department of Cardiology, University Hospital of Sabadell (Univ. Autonoma of Barcelona)


It is known that patients hospitalized for medical illnesses remain at risk for venous thromboembolism (VTE) after discharge and this can severely modify their long-term outcome. The role of extended out-of-hospital thromboprophylaxis in the treatment of these patients remains controversial. Several studies with different anticoagulants have shown either excess major bleeding or a benefit that is based mainly on reducing the risk of asymptomatic deep-vein thrombosis. Therefore, the authors analyzed the efficacy and safety of rivaroxaban versus placebo initiated after discharge and during 45 days in medically ill patients who had increased risk for VTE.

Trial design

MARINER is a randomised, double-blind, placebo-controlled, multicentric trial done in 36 countries. Eligible patients were aged >40 years, who had been hospitalized for 3 to 10 consecutive days (receiving thromboprophylaxis with heparin) and had one of the following conditions: heart failure (40% of included patients), respiratory insufficiency or exacerbation of chronic obstructive pulmonary disease (26%), ischemic stroke (14%), infectious disease (18%), inflammatory disease (2%). Also, they had additional risk factors for VTE as indicated by a total modified International Medical Prevention Registry on Venous Thromboembolism (IMPROVE) score of >4 or a risk score of 2-3 plus a plasma D-dimer level of more than twice the upper normal limit. The authors excluded patients who had a condition treated with anticoagulant or dual antiplatelet therapy, if they had active cancer, a history of recent bleeding (<3 months) or a high risk of bleeding. Patients were randomly assigned (1:1) to receive either placebo or 10 mg rivaroxaban once-daily if the creatinine clearance was >50 ml/minute or reduced to 7.5mg once daily if it was 30-50 ml/ minute. The trial agent was taken for 45 days. The primary efficacy endpoint was a composite outcome of any symptomatic VTE or death related to VTE. The secondary efficacy outcome was any symptomatic nonfatal VTE. The principal safety endpoint was major bleeding.


From June 2014 to January 2018, 12019 patients were enrolled and randomly assigned to receive rivaroxaban (n=6007) or placebo (n=6012) at 671 study sites. The primary endpoint occurred in 50 (0.83%) patients in the rivaroxaban group versus 66 (1.10%) in the placebo group (hazard ratio 0.76; 95% CI 0.52-1.09; p=0.14). The secondary (exploratory) endpoint occurred in 0.18% and 0.42% in the rivaroxaban and placebo-treated groups, respectively (hazard ratio, 0.44; 95% CI, 0.22-0.89, p<0.05). The safety endpoint of major bleeding occurred in 17 (0.28%) in the rivaroxaban group versus 9 (0.15%) in the placebo group (HR 1.88; 95% CI 0.84-4.23). There were 71 deaths in the rivaroxaban group (1.18%) versus 89  in the placebo group (1.48%) (HR 0.80; 95% CI 0.58–1.09).


Extended thromboprophylaxis with rivaroxaban to medical patients for 45 days after hospital discharge was not associated with a significant lower risk of symptomatic VTE and death than placebo. Major bleeding rates were low in both arms of treatment.


Based on the MARINER trial data and population, the number of patients needed to treat to prevent one symptomatic VTE event is 430, whereas the number needed to cause one major bleed is 856. Usually, patients with renal insufficiency have a higher incidence of thrombotic and bleeding events than patients with normal renal function. However, in this trail the results were concordant for patients with and without renal dysfunction. Overall, the trial included participants with lower thrombotic risk than expected. Thus, it remains to clarify which medical patients would really benefit from preventive out-of-hospital anticoagulation and the duration of the treatment.

Leave a Reply

Your email address will not be published. Required fields are marked *