A Word of Warning on Lysis Therapy

(Leipzig, Germany) January 31, 2020 -- Options for improving outcomes after catheter-directed intra-arterial thrombolysis, or lysis therapy, were discussed by Ulrich Beschorner, MD*, an executive senior physician within the Angiology Department at the University Heart Centre, Freiburg-Bad Krozingen, Germany.

Dr Beschorner, who is also the medical director of imaging analysis firm coreLab Black Forest GmbH, based in Bad Krozingen, explained there are particular contradictions in the use of this therapy. “Catheter-directed intra-arterial thrombolysis is a rational and well-used method for therapy of chronic limb ischemia (CLI) patients with thrombotic occlusions of lower extremity arteries or bypass grafts,” he said. “Unfortunately, the complication rate for lysis is not low.”

As a result, measures need to be taken to improve outcomes, continued Dr Beschorner. “It is important to systematically question our current treatment algorithms – ones that are often based only on personal experience. We should systematically examine which patients could really benefit from this therapy, and those who do not.”

Indeed, last year, a review¹ of 106 trials looked at the results and outcomes of different catheter-directed thrombolysis techniques. The researchers agreed that lysis is an effective treatment for peripheral arterial occlusions, but the main concern is bleeding complications. The review also suggested, although no meta-analysis could be done, that lower doses of fibrinolytics might lead to a longer treatment duration, but with similar success rates and, crucially, less bleeding.

Dr Beschorner recounted a recent case where lysis was considered a viable option. “It is quite easy to find examples of this,” he said. “Recently I saw an 85-year-old, multimorbid patient with CLI and long thrombotic occlusions of partially ectatic and partially stented superficial femoral and popliteal arteries. What would be the best endovascular treatment strategy for such a patient?”

Local lysis, possibly in combination with rotational thrombectomy and/or Gore Viabahn Endoprosthesis with Heparin Bioactive Surface (W.L. Gore & Associates) are options for the patient, said Dr Beschorner. “But perhaps we should still go open surgery?” he said. “If we go with lysis therapy, the question is should it be via continuous infusion or bolus technique? And at what dose? And for how long?”

In other words, there are many possibilities, but no evidence pointing to which might be most appropriate. “Everyone thinks they do it right, but then everyone does it differently, and nobody knows which is the right way,” said Dr Beschorner. “Unfortunately, we are far away from an evidence-based standardised therapy across different centers.”

The lysis method was developed in the early 1990s, said Dr Beschorner, and most of the data, such as the Thrombolysis or Peripheral Arterial Surgery (TOPAS) study², dates from this period. TOPAS compared recombinant urokinase with vascular surgery as initial treatment for acute arterial occlusion of the legs.  

Of course, much has changed since TOPAS, said Dr Beschorner.  “Endovascular therapy has developed considerably, and local lysing takes place in a completely different environment today using different techniques and thrombolytic agents,” he explained. Despite this, there are few studies that deal with local lysis therapy in the current context. “The evidence for local lysis treatment is even worse than it was in the late ‘90s,” he added.

However, there have been a few interesting findings recently, said Dr Beschorner, for example Grip et al’s study, looking at whether additional administration of heparin with ongoing lysis is of benefit or whether it only increases the risk of bleeding.³ “The group attempted to find risk factors for complications,” he commented.

In the study, the authors used a retrospective analysis of databases from two vascular centers. Importantly, one center used a higher dose of heparin and recombinant tissue plasminogen activator (rtPA) than the other. The group concluded that both treatment strategies were successful in achieving revascularization with acceptable complication rates. In other words, continuous heparin infusion during intra-arterial thrombolysis appeared to offer no advantage.

Dr Beschorner’s own center has also prospectively recorded the course of disease in lysis-treated patients over recent years. His team has summarized data from two years and, in addition to the prospectively collected data, retrospectively tried to obtain as much information as possible about their lysis patients from the patient curves and files.

With 5,676 percutaneous transluminal balloon angioplasties during this period, a total of 365 lysis procedures were consecutively included in the analysis and evaluated in detail with regards to all possible clinical and procedural parameters, said Dr Beschorner. “With this we tried to find out more about the possible risks of this therapy and to get information on which patient group is particularly at risk,” he explained.

“First analysis of this data reveals, among other things, that there is a significantly increased peri-interventional mortality, especially in elderly patients,” he said.

The results were unexpected: “I was surprised at the high complication rate this therapy still has, despite the use of more modern drugs, and the latest endovascular technology,” he said. “Compared to historical data from the 1990s, the risk of serious bleeding continues to be alarmingly high, but the success rate of the procedures has nevertheless improved significantly.”

As such, Dr Beschorner said the findings have made him more wary of using the technique. “I now have a great deal of respect for those initiating local lysis therapy,” he commented. “I use alternative thrombectomy methods whenever possible.”

 These include the Rotarex S (Straub Medical) mechanical atherectomy system, said Dr Beschorner. “Unfortunately, there will always be situations in which local lysis is unavoidable,” he added.

Looking forward, Dr Beschorner would like to see findings emerge from sufficiently large prospective randomized studies in order to confirm that when lysis therapy is mandated, it must be utilized as gently as possible. “We need a prospective, multicenter, randomized study that clarifies whether continuous heparin administration during ongoing local low-dose rtPA lysis really makes sense, or whether we should use other – or even no – concomitant anticoagulation,” he explained.

“In addition, the research must establish whether the additional use of modern mechanical thrombectomy systems could achieve a higher success rate with fewer complications,” he concluded.

[*Note: Dr. Beschorner was unable to present; Prof. Thomas Zeller presented on his behalf. This article is based on a pre-session interview with Dr. Beschorner.]

References

1. Ebben HP, Jongkind V, Wisselink W, et al. Catheter Directed Thrombolysis Protocols for Peripheral Arterial Occlusions: a Systematic Review. Eur J Vasc Endovasc Surg. 2019 May;57(5):667–675

2. Ouriel K, Veith FJ, Sasahara AA. A comparison of recombinant urokinase with vascular surgery as initial treatment for acute arterial occlusion of the legs. Thrombolysis or Peripheral Arterial Surgery (TOPAS) Investigators. N Engl J Med. 1998 Apr 16;338(16):1105–11.

3. Grip O, Kuoppala M, Acosta S, et. al. Outcome and complications after intra-arterial thrombolysis for lower limb ischaemia with or without continuous heparin infusion. Br J Surg. 2014 Aug;101(9):1105–12