Speaking on the FLAME, FLASH and PEERLESS trials that each collected data on the FlowTriever (Inari Medical) device for the treatment of pulmonary embolism (PE), Ripal Gandhi, MD, Miami Cardiac & Vascular Institute & Miami Cancer Institute, Miami, elaborated on the presiding safety and efficacy that is consistent throughout the research, and how these studies may shape future guidelines to better standardize the PE care pathway for physicians and patients.
Presenting at the 2023 International Vein Conference (April 27–29, Miami), Gandhi began by foregrounding the central focus of this work, stating that PE is the third leading cause of cardiovascular death worldwide, which often renders anticoagulation insufficient for patients with intermediate- or high-risk PE and/or long-term complications. Although several thrombotic therapies are known to be effective, Gandhi noted that there is a risk of bleeding, meaning not all patients are deemed eligible. As a knock-on effect of this, more devices have been brought to market to treat these patients, such as the FlowTriever device.
Speaking to Vascular Specialist about his presentation at IVC, Gandhi briefly discussed the main aims of the three studies and their results. First concerning the FLAME trial—the largest interventional trial done in high-risk PE patients Gandhi noted—he explained that the study was intended to enroll more participants but was concluded early after meeting the prespecified interim analysis criterion.
Principal investigator for the FLAME trial James Horowitz, MD, NYU Grossman School of Medicine, New York, and his team found that large-bore mechanical thrombectomy with the FlowTriever system in patients with high-risk PE was associated with a significantly lower occurrence of meaningful in-hospital adverse clinical outcomes compared to other contemporary treatments. In the FlowTriever arm, a mortality rate of 1.9% was recorded, compared to 29.5% in the context arm.
“It had to be [concluded prematurely]—the study was stopped at 50 patients because the results were so compelling. With the 17% endpoint in the FlowTriever arm versus 63.9% in the context arm, this was lower than the performance goal of 32%—much lower”, said Gandhi, commenting on FLAME’s results.
Turning his attention to the FLASH registry—the “largest interventional study ever done in PE”— Gandhi explained how the analysis drew from an 800-patient, prospective, multicenter, real-world registry. Led by Caitlin Toma, MD, University of Pittsburgh School of Medicine, Pittsburgh, the researchers’ main objective was to assess the safety and effectiveness of large-bore thrombectomy in an all-comer patient population through to six months.
Their primary endpoints were defined as any composite of major adverse events (MAE) within 48 hours. Their results showed a 1.8% MAE rate, with no device-related deaths. “This was quite remarkable,” Gandhi opined. “However, one of the most important things to look at is all-cause mortality at 30 days in this patient population, which was only 0.8%.”
“[In the FLASH registry] most of the patients did not require an intensive care unit day—as an interventionist the thing that is most gratifying when treating a patient who is very sick, is seeing immediate changes in their hemodynamic parameters on the table,” Gandhi described. “In treating patients with large bore thrombectomy, we see immediate changes in pulmonary artery pressures, improvement in their cardiac index and heart rate, and to see that in real-time is quite remarkable. It is extremely valuable.”
Briefly sketching out the intent for the currently ongoing PEERLESS trial, led by Wissam Jaber, MD, Emory University, Atlanta and Carin Gonsalves, MD, Thomas Jefferson University, Philadelphia, Gandhi averred that it is the “first and only” head-to-head randomized clinical trial comparing large-bore thrombectomy—via the FlowTriever system—with catheter-directed thrombolysis in PE patients.
“We happen to be one of the enrolling sites,” Gandhi said, noting that enrolment is currently at its halfway point. “[PEERLESS] is one of several randomized clinical trials that are being done in this space right now and this is an important one, however we definitely need more research.”
Amongst the research emerging for the treatment of PE, Gandhi makes clear that better standardized care pathways are the “goal”, although it will not “happen overnight”. “In most of our hospitals we have rapid care pathways for patients who present with ST elevation myocardial infarction or stroke, but we should have similar pathways for patients presenting with high-risk PE”. Gandhi emphasized the invaluable nature of trials such as these in helping to “guide” physicians in the future, and to inform them on how best to manage these patients.