FLARE: Mechanical Thrombectomy Effective in Intermediate-Risk PE

Patrice Wendling

May 01, 2018

Upfront catheter-directed mechanical thrombectomy without use of thrombolytics appears to improve right ventricular strain in patients presenting with intermediate-risk acute pulmonary embolism (PE), results of the Flowtriever Pulmonary Embolectomy Clinical (FLARE) study suggest.  

Right-to-left ventricular (RV/LV) ratio, which has reliably correlated with symptomatic improvement and PE-related mortality, declined 0.39 from baseline when assessed 48 hours after thrombectomy with the investigational Flowtriever device (Inari Medical) (mean, 1.53 to 1.15; P < .0001).

Among the 106 patients, there was no intracranial hemorrhage, access-site VARC-2 major bleeding, or device-related deaths or injuries. There were four major adverse events, Thomas Tu, MD, Baptist Health, Louisville, Kentucky, reported at the Society for Cardiovascular Angiography and Interventions (SCAI) 2018 Scientific Sessions.

"I think it's a huge breakthrough because we're always searching for better treatments for this very morbid and mortal disease," Tu said in an interview. "Pulmonary embolism is the number three cause of cardiovascular mortality, and it's one of these disease states that we haven't really done a lot of new stuff with for quite some time. We've had anticoagulation, and maybe some new anticoagulants, but really a rethink of the whole disease process and how to approach it has just started."

He noted that the concept of the PE response team (PERT) and arrival of new devices, however, are drawing people out of a kind of therapeutic nihilism.

"I was just involved in a pulmonary embolism breakout-session at 6:30 am today and I was shocked that it was standing room only," Tu said. "Three or four years ago, there would be a handful of people in the room interested in pulmonary embolism, but now I think finally cardiologists are really taking an interest in this disease state and I think we're going to see things move forward very rapidly."

Rapid Flow Restoration

The Flowtriever system features an aspiration-guide catheter that is advanced through the veins into the pulmonary artery, disks that engage and macerate the clot, and a retraction aspirator that withdraws the clot back into the catheter.

From April 2016 to October 2017, trialists at 18 sites enrolled 106 patients with PE symptoms for 14 days or less and an RV/LV ratio at least 0.9.

Main exclusion criteria were thrombolytic use within 30 days, pulmonary hypertension with peak pulmonary artery pressure more than 70 mm Hg, vasopressor requirement after fluids to keep pressure at least 90 mm Hg, fraction of inspired oxygen requirement more than 40% room air or more than 6 L per minute to keep oxygen saturation greater than 90%, hematocrit less than 28%, platelets less than 100,000/μL, serum creatinine more than 1.8 mg/dL, international normalized ratio more than 3, cardiovascular or pulmonary surgery within 7 days, or actively progressing cancer. There was no specific exclusion for increased bleeding risk.

The patients' mean age was 55.6 years, 54.7% were male, 82.1% were white, and 17% were African American. Bilateral PE was present in 50.9%, bilateral plus central PE in 39.6%, and concurrent deep-vein thrombosis in 68.9%; 9.4% had a prior PE.

The mean procedure time was 1 hour 39 minutes and 95.3% of procedures were right femoral access. Unfractionated and low-molecular-weight heparin were used preprocedure in 83% and 20.8% of patients, respectively. Only two patients received lytics during the procedure.

"The patients I would say quite often will feel better immediately on the table. In fact, not even just on the table, but at the time that the clot is removed they feel it, they feel better," Tu said. "Patients are leaving the cath lab saying, 'I feel like I'm breathing back to normal.'"

The reduction in RV/LV ratio at 48 hours compares favorably with those observed in two ultrasound-assisted, catheter-directed thrombolysis trials, SEATTLE 2 (ratio 0.42) and ULTIMA (ratio 0.29).

The median intensive care unit (ICU) stay was 1 day, with 44 patients having no ICU stay. Median time to discharge was 3 days.

Jay Giri, MD, MPH, Hospital of the University of Pennsylvania, Philadelphia, who was not involved with the study, told theheart.org | Medscape Cardiology, "What I think this tells us, which is useful information, is that you can reliably walk into a symptomatic patient's room and say that they are likely to feel better faster with this device than if managed with conservative anticoagulation alone."

The ability to skip thrombolytics is "huge" and "almost certainly" eliminates the concomitant risk for intracranial hemorrhage, he said. But there's also a lot of information the single-arm study doesn't provide, such as whether patients will feel better long-term or whether the therapy provides any differences in short- or long-term mortality or the development of chronic thromboembolic pulmonary hypertension, compared with conservative therapy.

Giri said it is similarly difficult to make decisions based on longer-term outcomes with systemic lysis and ultrasound-assisted, catheter-directed lysis, the only other options that have been tested to the same degree in this population. But in both of those options, "what you can say to the patient is almost the same" in terms of feeling better, faster, than with anticoagulation.

"To be breakthrough therapy, which means being utilized in a fairly wide array of patients, I would argue you need to show fairly ongoing and impeccable results for safety," he said. "And those safety metrics are safe in the lungs, safe from a cardiopulmonary standpoint from cardiopulmonary decompensation, and safe from a bleeding standpoint, most importantly intracranial bleeding but also off-target bleeding," particularly given Flowtriever's large-bore catheter, he said.

Tu said the FLARE trial "gets at the question of whether this form of therapy is safe and effective, and the answer is 'yes.' I think it remains to be seen from a strategic standpoint where people feel most comfortable because some people would say in an intermediate-risk population, 'I only want to do something that is extremely safe.' And where they are going to draw the line is up for debate."

Major Adverse Events

Four patients had major adverse events (3.8%), which included pulmonary infarction with possible reperfusion injury, worsening PE requiring surgical embolectomy, cardiogenic shock, and respiratory arrest requiring cardioversion in an agitated patient.

"There is definitely a learning curve to this procedure," Tu said. "The placement of a 20-French sheath in the pulmonary artery is not something that even experienced interventionalists do on a regular basis. Additionally, imaging of the clot and precise placement of the Flowtriever disks and evacuation catheter are critical for success."

Tu suggested it would take about five cases for an experienced physician to become facile with the technique and that their procedure time is now around 60 minutes.

"I think the learning curve helps with patient selection, speed of procedure, and technique —  all of which could play a role in preventing these types of events," he said.

Andrew John Klein, MD, Piedmont Heart Institute, Atlanta, Georgia, said in an interview that these were highly skilled interventionalists and "If you put this in a large registry I think there will be some device-related complications, obviously. That's going to happen. It's a large device."

That said, he noted that FLARE was performed with an older, bigger, and bulkier iteration of the device, yet the Flowtriever is still easier to traverse and better tolerated than the large-bore AngioVac device (AngioDynamics).

Fitting Into the PE Paradigm

Klein agreed that catheter-directed therapy for PE is still in its infancy, likening it to the early 1980s when coronary intervention and angioplasty first came on board. Until there's a large randomized trial showing a hard outcome like mortality benefit, he said, the FLARE results are unlikely to shift the naysayers, "but it is going to perhaps provide us with another tool on the table."

Exactly where mechanical thrombectomy fits into the PE treatment paradigm remains to be seen, but Klein said reserving the Flowretriever for failed lytics cases would be a mistake and result in poor outcomes. Also, the novel device should not be overlooked in the 2.5% to 5% of patients with massive PE, whose in-hospital mortality rates range from 25% to as high as 70%.

"For patients that are going to go on to catheter-directed therapy who are in the massive group, I think this is going to be a great device," Klein said. "These are the patients that are literally dying in front of you. So getting that clot out as quickly as possible is going to help improve your hemodynamics; it's going to make your patients feel better."

Nationally, these high-risk patients are tremendously undertreated with advanced therapies, whether it's systemic or catheter-directed lytic therapy or surgery, said Giri, a member of the PERT Consortium board of directors. Part of the problem is that they tend to have high rates of relative or absolute contraindications to thrombolytic therapy, which the Flowtriever avoids.

"How patients react, especially sicker patients when you have this large-bore device in there, is still an open question," he said. "That being said, if it ends up getting an FDA clearance based on this, it wouldn't surprise me if different institutions were thinking in some of these very difficult clinical scenarios this is an option to try to do something to save this person…especially the ones with relative or absolute contraindications to thrombolysis."

Tu disclosed no relevant relationships. Stein reported serving on an advisory board for Medtronic. Giri serves on the board of directors for the PERT Consortium.

Society for Cardiovascular Angiography and Interventions 2018 Scientific Sessions. Presented April 27, 2018.

Follow Patrice Wendling on Twitter: @pwendl. For more from theheart.org | Medscape Cardiology, follow us on Twitter and Facebook.

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