Alex C. Spyropoulos
MUNICH — In medically ill patients at risk for venous thromboembolism, rivaroxaban did not improve the composite endpoint of symptomatic VTE or death due to VTE, according to the results of the MARINER study.
However, rivaroxaban (Xarelto, Janssen) was superior to placebo in reducing symptomatic VTE alone, and bleeding rates were low, researchers reported at the European Society of Cardiology Congress.
“There’s a very large unmet medical need in acutely medically ill patients, especially in the post-discharge period,” Alex C. Spyropoulos, MD, professor of medicine at the Donald and Barbara Zucker School of Medicine at Hofstra/Northwell and professor at the Feinstein Institute for Medical Research, told Cardiology Today. “The standard of care … is actually doing nothing. Less than 1% of these patients get anything in terms of post-discharge prophylaxis. Yet, about 80% of VTE events in this population occur in the post-discharge period.”
He noted this population, which includes patients with HF, stroke, inflammatory diseases and other conditions, tends to experience worse VTE events than the surgical population due to being older, having more comorbidities and having limited cardiopulmonary reserve.
Spyropoulos and colleagues randomly assigned 12,024 medically ill patients at elevated risk for VTE based on an IMPROVE score of 4 or higher or a score of 2 or 3 if they also had a plasma D-dimer level more than twice the upper limit of normal to receive rivaroxaban 10 mg daily (adjusted to 7.5 mg per day for moderate renal insufficiency if necessary) or placebo for 45 days. Patients were followed for 30 days after the 45-day period.
The primary endpoint was symptomatic VTE or VTE-related death. The key secondary endpoint was nonfatal symptomatic VTE. The key safety endpoint was major bleeding.
There was no significant difference in the primary endpoint in the intention-to-treat population (rivaroxaban group, 0.83%; placebo group, 1.1%; HR = 0.76; 95% CI, 0.52-1.09), according to the researchers.
However, nonfatal symptomatic VTE was lower in the rivaroxaban group (0.18% vs. 0.42%; HR = 0.44; 95% CI, 0.22-0.89), Spyropoulos said.
Major bleeding rates were low and did not significantly differ between the groups (rivaroxaban group, 0.28%; placebo group, 0.15%; HR = 1.88; 95% CI, 0.84-4.23), according to the researchers.
In addition, Spyropoulos said, the rivaroxaban group had a 27% reduction in symptomatic VTE and all-cause mortality (HR = 0.73; 95% CI, 0.54-0.97).
The treatment effect for the primary outcome was stronger among those given the 10-mg dose of rivaroxaban vs. the 7.5-mg dose; during a press conference, Spyropoulos said there was “no future” for the 7.5-mg dose in this population.
“We achieved reductions in two important secondary outcomes, which should be considered exploratory,” Spyropoulos said in an interview. “These, combined with the low rates of bleeding, show that the strategy is very safe. If one is able to identify the appropriate patients, such as was done with the individualized approach in MARINER, especially in the U.S. hospital system with shorter lengths of stay, we could expect a reduction in symptomatic VTE, about half of which are nonfatal pulmonary emboli. Even though the absolute risk difference was small, we probably could save about 10,000 nonfatal PEs in the U.S. and European Union annually at the cost of one-tenth of that number of fatal or critical bleeds.”
The data were simultaneously published in The New England Journal of Medicine. – by Erik Swain
Spyropoulos AC, et al. Hot Line Session 1. Presented at: European Society of Cardiology Congress; Aug. 25-29, 2018; Munich.
Spyropoulos AC, et al. N Engl J Med. 2018;doi:10.1056/NEJMoa1805090.
Disclosures: The study was funded by Janssen. Spyropoulos reports he consults for Boehringer Ingelheim, Janssen and Portola. Please see the study for a list of the other authors’ relevant financial disclosures.