Dr. Sam Goldhaber discusses the results of the MARINER trial. As an added bonus, Dr. James Welker provides his commentary.
This is Dr. Sam Goldhaber for Clot Chronicles, speaking to you about the results of the MARINER trial, which were presented at the European Society of Cardiology meeting in Munich. MARINER was a 12,000 patient trial designed to reduce death, pulmonary embolism (PE), and deep vein thrombosis (DVT) during the first month after hospitalization in patients hospitalized with medical illness.
In this trial, at the time of hospital discharge, patients were randomized either to receive rivaroxaban or its placebo. Then, they were followed to see whether they survived, whether they developed a clinical episode of PE, or a clinical episode of DVT. It turned out that the primary endpoint of reducing the venous thromboembolism-related (VTE) mortality and reducing the PE and DVT, all as a combined endpoint, was not met. However, a secondary endpoint of reducing symptomatic DVT and PE was met in the MARINER trial, where rivaroxaban was superior to placebo.
I think this gives us an interesting option. It’s not an FDA-approved regimen for patients being discharged from the hospital, but it’s something that I think should be considered by the FDA. We already have one FDA-approved anticoagulation regimen with betrixaban. Betrixaban in the APEX trial of medically ill hospitalized patients actually started the betrixaban during hospitalization, rather than at the conclusion of hospitalization, and continued betrixaban for a total of 35-42 days and found a reduction in asymptomatic PE and DVT, a reduction symptomatic PE and DVT, a reduction in stroke, a reduction in fatal and irreversible events, and a reduction in VTE-related re-hospitalization within 30 days.
So, I think that the APEX trial with betrixaban and the MARINER trial with rivaroxaban are both telling us that this one month after hospital discharge is a critically important month with a high PE and DVT event rate. Now, we have anticoagulation regimens that address this specific issue.
This is Dr. Sam Goldhaber signing off for the Clot Chronicles.
Bonus: Dr. James Welker weighs in.
Hello, this is Dr. James Welker, I am the Director of Advanced Medical Therapeutics for Anne Arundel Health System and have been given the opportunity to comment on the VTE prevention population and trials for which Dr. Goldhaber has provided an excellent review in today’s Clot Chronicles.
The MARINER trial is the most recent of five high-quality studies assessing medical prophylaxis in patients with recent hospitalization due to a non-surgical illness. These began with the EXCLAIM trial, and includes ADOPT, MAGELLAN, APEX and now MARINER trials. We began with the idea that post-hospitalization anticoagulation may be helpful for medical patients, but initially found that any reduction in VTE was offset by excess bleeding in early trials.
In today’s Clot Chronicles, Dr. Goldhaber described the MARINER and APEX trials that, by optimizing the treatment selection and patient population, were able to demonstrate the described benefits with a reduction of the bleeding risk. In addition to Dr. Goldhaber’s review, it is notable that the APEX trial accepted a broader range of patients of the two trials. MARINER’s patient selection was dependent on the IMPROVE score, excluded patients with GFR <30 mL/min and reduced the dose for GFR 30-50 mL/min, whereas the APEX patient population was heavily influenced by age and D-dimer and included a broader range of chronic kidney disease (CKD) patients by including patients with a GFR as low as 15 mL/min and dose adjustment for those 15-30 mL/min. Both trials cautiously excluded patients with an increased risk of bleeding, and while patients with active cancer were included in the APEX trial, these were excluded from the MARINER trial. While continued review of APEX trial data identified the described broad range of patient benefits, the MARINER trial has just completed it primary data analysis.
As we consider how to utilize this new information, I believe the following questions will help us:
- What additional benefits will be identified with further analysis of the rivaroxaban trial data that may include data from both the MARINER and MAGELLAN trials? These two trials provide a large data set to analyze for rivaroxaban. How will these additional findings compare to those found from the APEX trial? How will the regulatory bodies analyze the data? These questions will impact labeling and clinician medication selection.
- Finally, how will hospitals deal with patient selection? These trials have become increasingly selective of the patient population, which has resulted in the demonstration of benefits in more narrow populations. This creates the need for health systems to develop methods of applying these refined treatments to a population with a similarly low bleeding risk to realize this same patient outcomes.
This is Dr. James Welker signing off from the Clot Chronicles.