Krishna Rocha-Singh, Prairie Vascular Institute, Springfield, USA, questioned the clinical relevance of the DESTINY, ACHILLES and YUKON trial designs at the annual LINC meeting in Leipzig, Germany.
He told delegates, “Marc Bosiers, Thomas Zeller and Dierk Scheinert are to be congratulated for their excellent work demonstrating that…
- Interventions using coronary drug-eluting stents below the knee in claudicants (Rutherford category 2 to 3) is a new, emerging study inclusion criteria
- You can do trials in patients with ischaemic limbs while excluding Rutherford Category 6 patients
- Coronary drug-eluting stents have superior binary patency rates compared to percutaneous transluminal angioplasty/bare metal stents in patients with so-called “ischaemic limbs” with mean lesion lengths less than 3cm.
“Was anyone in this audience really surprised that coronary drug-eluting stents would have a superior technical success rate compared to angioplasty? Or that the binary patency rates of coronary drug-eluting stents were going to be superior to angioplasty or bare metal stents? Or even that we continue to do below-the-knee drug-eluting stents studies which focus on stent patency as a primary endpoint, rather than “patient-centric” outcomes in patients with critical limb ischaemia?” Rocha-Singh asked.
Going beyond the coronary paradigm in study design
“How clinically relevant is six to 12-month index vessel patency? How does it translate into more ‘patient-centric’ surrogates such as limb preservation, pain control, maintenance of function and mobility and wound healing?” Rocha-Singh argued.
“Patients do not necessarily want to know whether the stent I have put in is patent or not. They want to know about their limb preservation, they want to know about their pain control, they want to know about their maintenance of mobility and function and they want to know about wound healing. At this stage I must acknowledge that Marc Bosiers did look at wound healing and my hope is that Dierk Scheinert in his primary manuscript will look deeper at that because I do think that it is essential. So I am suggesting here that all of us look beyond the coronary paradigm when we start dealing with below-the-knee study designs,” he said.
He also pointed out that there were patient vs. physician-centred outcomes and that lessons learned from the surgical literature had shown that graft patency is equated with a successful clinical outcome and amputation-free survival.
“However, graft patency and its association with other ‘patient-centric’ outcomes such as symptom relief, wound healing and mobility are poorly correlated and these are very complex patients,” he said.
Patency is only part of the answer, he said. Pointing to the literature, Rocha-Singh highlighted that in a 2007 study (Taylor et al, Journal of American College of Surgery) which set out to determine success after bypass for critical limb ischaemia, clinical success was defined as achieving all of the following: graft patency to the point of wound healing, limb salvage at one year, maintenance of ambulatory status at one year and survival for six months.
The results of this study which enrolled 331 patients with Rutherford class 3–6 lesion, showed that graft patency and limb salvage at three years was 73%, but the total clinical success when combining all four of the parameters was only 44%.
“For below-the-knee lesions, expensive technologies should yield better patient-relevant outcomes—perhaps an adequate percutaneous transluminal angioplasty result alone is sufficient. Although an important element, in the USA, payers will not reimburse for ‘stent patency’. We must challenge each other to promote rigorous trial designs to advance this field beyond technology-driven surrogates,” Rocha-Singh said.