It wouldn’t be Charing Cross without a little controversy. The talk on clot lysis and thrombolytic therapy raised some interesting issues and stimulated good audience discussion.
Jacob Cynamon (New York, NY) started by talking about combination (pharmo-mechanical) thrombolysis using the Angiojet from Possis. “Severe lesions can lead to deep vein thromboses (DVTs),” he observed. “But why venous lysis? We believe it helps prevent post-phlebitic syndrome and is most effective in patients with lilo-femoral DVT.” However, the time for the procedure – at anywhere between 24 and 72 hours – is a real drawback. Three days for one procedure is too much in many cases, therefore a mechanical device is very important. “However, more important than the devices is early stenting of the iliac system.”
The power pulse was initially employed in the arterial system, then moved into the venous system, Cynamon explained. The Angiojet device works by closing off the return so that instead of the fluid being sucked back into the catheter it is pulsed out, ensuring the lytic agent penetrates the clot. “We describe it in the dialysis world as ‘lyse-and-wait’,” he commented. “You allow the clot to dissolve for half an hour then go back and aspirate.” Plus, the device has been designed to prevent air from getting into the system. “In conclusion, venous thrombosis does lead to significant clinical sequalae. Thrombolysis is safe and effective, and power lysis is probably safe and effective and can be completed in a fraction of the time. Large series and long-term follow up is necessary.”However, existing thrombolytic agents are plasminogen activators that have untoward side effects. Gunnar Tepe (Tubingen, Germany) introduced alfimeprase (from Nuvelo), which is a novel direct-acting fibrinolytic and not a plasminogen activator. “There are several treatment options for acute thrombotic occlusion of the arteries. One is plasminogen activators, but there are limitations. Most are used off-label, there is a risk of major complications such as bleeding, there might be intracerebral bleeding, and it’s very time consuming.” Mechanical devices, he added, have questions around their efficacy. “Of course they work but they require big sheaths and they often require concomitant activators later on.” Surgery is also a limited treatment modality, he claimed.
Tepe presented alfimeprase, which is practical as it acts directly on the fibrin, so that its activity is confined to the site of delivery and is rapidly inactivated in the general circulation by alpha-2 macroglobulin. In terms of safety, lytic activity is confined to the delivery site and alfimeprase does not generate a systemic lytic state. “Correlated to these features, the drug might be quicker than other thrombolytic drugs and also safer,” he proposed.
Tepe spoke about the early safety trial of alfimeprase. “They found no serious adverse events related to the drug, and only minor bleeding events,” he revealed. “There were three minor adverse events related to the drug, including headache and rash.” He also introduced unpublished data from a Phase II dose escalation trial in 113 patients that showed a dose-dependent response (although non significant). “The results of this trial were that alfimeprase was safe and well tolerated with no systemic or intracranial bleeding. There were low rates of hypotension and peripheral embolisation, and very important no antibodies were detected against alfimeprase.”
Alfimeprase is currently in two multinational Phase III trials for acute peripheral arterial occlusion and two multinational Phase III trials for central venous catheter occlusion. “We await the data at the end of the year,” he concluded.
Finally, Kim Hodgson (Springfield, IL) spoke about his rationale for thrombolysis. “What exactly are we trying to achieve? Complete and stand-alone vessel recanalization would be ideal. However, that’s rarely achieved with supplemental angioplasty and other interventional procedures required. Perhaps this would be possible for embolic occlusions, but often the age of the clot is a limitation.” He added that chronic clot is considered stable and can be treated like plaque.
In contrast to the other speakers, Hodgson took a purely mechanical approach to clot busting with the Rotarex rotational thrombectomy system (Straub). Rotarex is not available in the US. “I have no personal experience with this device, but I won’t let that stop me from having an opinion about it,” he stated. The Rotarex is a coated stainless steel over the wire spiral rotating at 40,000rpm. It has a dual blade cutting crown to ‘detach’ the thrombus, and is available in 8Fr and 6Fr sizes; the former being associated with a high rate of complications. It is a wall-contact device.
Hodgson presented results from a recent trial in 19 patients. “I’d like to draw your attention to the 32% complication rate. 10% had perforations, 5% AV fistula, and 15% distal embolisation. And the results are not all that impressive in terms of long-term results,” he commented. A larger trial in Germany and Switzerland had a primary success rate of 92%, but again the complication rates were high. “I’m really concerned that this is not so much a rotational thrombectomy as more of an uncontrolled atheroectomy device,” Hodgson commented. He touched upon the Bacchus Vascular Trellis device for more localized treatment, but time was against him. “In conclusion I continue to use combination lysis.”
The audience discussion was started by a doctor from Aberdeen who questioned Cynamon on the need to place filters when lysing clots. “From the perspective of the NHS this adds considerable cost to the procedure.” Cynamon replied, “In America we don’t consider it to cost that much!” And while he admitted seeing clot matter in filters when removing them, this does lyse with a second Angiojet procedure. The questioner then turned to Hodgson to defend the Rotarex. “I always use the 6Fr size – the 8Fr is rather unwieldy. It’s very effective.”