Kuo, Stanford, USA, argued that the lack of level 1 data should not be used to withhold catheter-directed therapy, since it is a live-saving manoeuvre like using a parachute. “Just imagine a world in which crucial decisions were based solely on the availability of prospective level 1 data,” he said.
He said that ongoing studies such as the PERFECT (Pulmonary embolism response to fragmentation, embolectomy and catheter thrombolysis) registry for massive and submassive pulmonary embolism and the SEATTLE II trial for submassive pulmonary embolism would help refine current treatment protocols and provide further evidence supporting catheter-directed thrombolysis.
“Despite its labelled indication, systemic tissue plasminogen activator (tPA) is not a safe and effective treatment for acute pulmonary embolism and it is contraindicated in most patients with acute massive and submassive pulmonary embolism,” he said. Kuo then drew attention to the American College of Chest Physicians (ACCP) Guidelines on antithrombotic therapy for venous thromboembolism. He pointed out that while in 2008, the ACCP had harshly recommended against catheter intervention for pulmonary embolism, the updated 2012 guidelines have downgraded their recommendation for intravenous (IV) tPA based on best current evidence (grade 1C in 2008; 2C in 2012) and upgraded their recommendation for catheter intervention which is safer and more effective according to best current evidence.
Kuo said, “Acute pulmonary embolism patients are poor surgical candidates and the treatment can be worse than the disease. Surgical management of acute pulmonary embolism has been abandoned at most centres because of high morbidity and mortality from the operation. Systemic tPA is standard FDA-approved treatment for the lysis of pulmonary embolism accompanied by unstable haemodynamics. Since patients in shock from massive pulmonary embolism are at greater risk of haemorrhagic complications, full dose IV tPA is actually contraindicated in most patients with acute pulmonary embolism. Catheter intervention is much better as it is less invasive than open surgery, can quickly debulk the central pulmonary embolus (no two-hour IV tPA infusion is required), can be initiated mechanically with low or no dose thrombolytic (which is safer than full-dose tPA) and useful when intravenous tPA is contraindicated. A 2009 meta-analysis showed that the pooled clinical success rate of catheter-directed therapy was 86.5% [82.1%–90.2%] (JVIR, Kuo et al).”
Trerotola, Philadelphia, USA, made the point that the arguments against catheter directed thrombolyisis for pulmonary embolism were based on the current evidence (or lack thereof). He told delegates that to date, there was no randomised controlled trial proving the efficacy of the therapy over the standard of care. “One trial is underway, ULTIMA, which randomised ultrasound-assisted tPA lysis to heparin therapy. “We must prove that we can change the course of the disease. The burden of proof rests on interventional radiology, and a registry will not accomplish this. A randomised controlled trial is absolutely ethical given the standard of care,” he noted.
In terms of resources, Trerotola asked delegates in the room, “If you were dying of pulmonary embolism, would you rather be in the intensive care unit or in an interventional radiology suite, from a support standpoint?” Referring to time to therapy in massive pulmonary embolism, he questioned how quickly an interventional radiology team could mobilise. Also, “Transporting patients to interventional radiology risks death in an elevator,” he said.
“With regard to industry influence, interventional radiology needs support and possibly funding. The industry should not be promoting off-label use, and should not be designing trials. They should be our partners, not drivers,” Trerotola said.
“We must obey the principle of ‘first do no harm’, with catheter-directed thrombolysis, there is a lot of opportunity for harm and no proven benefit. Agents of change carry the burden of proof to show that this procedure is not just for volume and money. We need evidence to show that this is not just a costly unproven, risky procedure vs. a lifesaving innovation,” he added.
Then, Angle, Virginia, USA, made the point that anticoagulation (eg heparin) has been around for over 75 years. “IV tPA has been available to, and promoted by intensivists for over 35 years. Still there are roughly 300,000 deaths a year in the USA due to pulmonary embolism, so the current plan (heparin with occasional IV therapy) is not working.” He also noted that it was a common misperception that only randomised trials form evidence-based medicine. “Evidence-based medicine stresses finding the best available evidence to answer a question,” he noted citing Straus SE, Canadian Medical Association Journal, 2000.
Vedantham, St Louis, USA, then took the podium to share some “home truths” for the interventional radiology innovator. He told delegates that interventional radiology should not personify the failings of American Medicine. “Methodology matters, and the meta-analysis by Kuo et al included some deeply flawed studies including open label studies with non-blinded assessors, six prospective studies and small sample numbers. Publication bias is certain when the physician assesses their own treatment results, and decides whether to publish, how to report and which cases to omit,” he said.
Vedantham also cautioned that innovation by itself is overrated. As an example, he noted that while thrombolysis for deep venous thrombosis may ultimately prove to offer great clinical value, its premature promotion was viewed as irresponsible by medical physicians, delaying meaningful scientific collaboration for many years. He cautioned that "since pulmolary embolism thrombolysis also presents potential risks to the patient, it is important to demonstrate its efficacy before promoting the procedure."