The audience in the CIRSE 2014 “Controversies in superficial femoral artery treatment” session failed to endorse two motions pertaining to drug-elution in this anatomical segment in the annual meeting (12–17 September, Glasgow, UK). The first motion was “drug-eluting stents will show better five-year patency rates than percutaneous transluminal angioplasty” and the other was “Drug-eluting balloons in all superficial femoral artery lesions”. While the majority vote went against both motions, leaving the proponents of drug-eluting devices disappointed, experts have questioned whether a motion that was more specific with respect to lesion type and length might have elicited a different voting result.
At CIRSE 2014, an unexpected voting turnaround was brought about by Nick Chalmers, Manchester, UK, who debated against Konstantinos Katsanos, London, UK, in the session. Chalmers was speaking against the motion “drug-eluting stents will show better five-year patency rates than percutaneous transluminal angioplasty”.
A pre-debate poll showed that 74% voted in favour of the motion, just before the debaters took to the podium, which suggested that Katsanos would have an easy task ahead. Katsanos first outlined the armamentarium (in which drug-eluting stents and drug-eluting balloons are the latest entrants) available to the interventionist in the fight against restenosis. The fight against restenosis, Katsanos said, was akin to a Sisyphean task. He drew attention to the fact that drug-eluting stents conferred a slow-release of paclitaxel or rapamycin in the superficial femoral artery and that both drugs had a proven effectiveness in coronary arteries. He also outlined the differences between paclitaxel and “olimus” drugs such as everolimus or sirolimus which were the drugs eluted from the drug-eluting stents in the STRIDES and SIROCCO trials (which did not show a benefit for drug-eluting stents over bare metal stents) and compared this to the ZILVER PTX trial whose four-year results have shown that freedom from target lesion revascularisation using drug-eluting stents is far greater than that achieved with bare metal stents.
Chalmers then based his arguments around the importance of clinically relevant endpoints and cost-effectiveness to persuade a large section of the audience to change their minds. He argued that drug-eluting stents offer “some reduction in reintervention rate in the first year”, but offer no real clinical benefit, no improvement in secondary patency and no additional benefit beyond year one, and all at substantial additional cost.”
At the end of the debate, just 41% voted for the motion and 59% were against the motion.
Jim A Reekers, Amsterdam, The Netherlands, told Interventional News that he thought the pre-debate vote of 74% in favour of drug-eluting stents showing better five-year patency rates was rather surprising, and that he believed that this showed that “marketing works”. He referred to the results of a recent publication by his group in The Netherlands (Randomised trials for endovascular treatment of infrainguinal arterial disease: Systematic review and meta-analysis (part 1: above the knee, S Jens et al, published online in February in the European Journal of Vascular and Endovascular Surgery) which set out to evaluate one to 36-month follow-up outcomes of different endovascular treatment strategies in above-the-knee arterial segments in patients with intermittent claudication and critical limb ischemia. The paper highlighted that 23 trials including 3314 patients in total were identified. Eighty five per cent patients had intermittent claudication and 15% critical limb ischaemia. The paper also showed that 15 trials showed no systematic benefit of bare metal stenting over percutaneous transluminal angioplasty. One trial comparing drug-eluting stents and angioplasty reported no significant differences in walking capacity or Rutherford classification. Four trials showed a beneficial effect on target lesion revascularisation rate, but not on Rutherford classification of drug-eluting balloons compared with angioplasty. In four trials, drug-eluting stents did not systematically perform better than bare stents. Jens et al concluded that in general, performing percutaneous transluminal angioplasty with optional bailout stenting for lesions above the knee is currently still the preferred strategy in patients with intermittent claudication. For critical limb ischaemia, more studies are needed for recommending an optimal treatment strategy, the authors wrote.
One of the most pressing issues of the day is clarity on the place of various technologies for the superficial femoral artery segment and this will be a focus at the next Charing Cross International Symposium (28 April – 1 May 2015, London, UK).
Brian Stainken, one of the editors-in-chief of Interventional News commented that the voting results could reflect the growing maturity of interventional radiologists with regard to the embracing of new technologies. “In the past, we have seen the cycle of new technologies being taken up and endorsed too quickly before there is clear-cut evidence to support their use and this voting perhaps shows that interventional radiologists now want to see high-quality evidence with long-term follow-up before they cast their vote in support of widespread use for newer technologies,” he noted.
The majority of voters at the same session at CIRSE 2014 did not also agree with the motion “Drug-eluting balloons in all superficial femoral artery lesions”. Before the debate, 76% of voters did not agree with the motion, and just 24% did. Gunnar Tepe, Rosenheim, Germany, who spoke for the motion managed to convince a further 6% of the voters to switch to voting for the motion leaving the final vote at 70% against and 30% for.
Tepe made the point that there was not only a high degree of enthusiasm but also a high grade of evidence that drug-eluting balloons are safe and effective in the superficial femoral artery. “Best outcomes have been reported by the IN.PACT drug-coated balloons in the femoropopliteal region through one of the broadest and highest quality clinical programmes so far,” he said. “Based on the results of the two control groups seen in ongoing drug-coated balloon trials, I cannot justify not using these devices,” he told delegates.
In the first-ever presentation of 12-month data from the randomised multicentre IN.PACT SFA trial at the Charing Cross Symposium earlier in April this year, Tepe revealed that treatment with the IN.PACT Admiral drug-eluting balloon (Medtronic) was significantly superior to percutaneous transluminal angioplasty in terms of reinterventions and patency.
The randomised controlled IN.PACT SFA trial which is as-yet unpublished showed that clinically-driven target lesion revascularisation rates were significantly lower with the drug-eluting balloon as compared to those achieved with angioplasty (2.4% vs. 20.6%, p<0.001). Similarly, the primary patency rate achieved with the IN.PACT Admiral drug-eluting balloon was 82.2%, while the primary patency achieved with angioplasty was 52.45% (p<0.001). Primary patency at 360 days was also calculated by Kaplan-Meier survival estimates; at this specific time point, it was 89.8% for the drug-eluting balloon group and 66.8% for the angioplasty group.
At Charing Cross, Tepe, Rosenheim, Germany, said: “There is robust level 1 evidence to show that the IN.PACT Admiral drug-eluting balloon has achieved the lowest target lesion revascularisation and highest patency rates ever reported with an endovascular therapy in the superficial femoral artery.”
Following the presentation of the IN.PACT SFA data, the voting results at the Charing Cross Symposium 2014 captured a shift in audience perception regarding the value of drug-eluting balloons in peripheral arterial disease. While just two years ago, a poll identified that 27% viewed drug-eluting balloons as an alternative to stents, in 2014, 72% voted that they did so.
The audience response polls also revealed that nearly 90% voted that drug-elution was worthwhile in the superficial femoral artery. In 2013, just 57% cast their vote stating that drug-elution was worthwhile in this anatomical region.
At CIRSE 2014, Marcus Katoh, Krefeld, Germany, referred to the published data so far from the randomised controlled trials which include the THUNDER, FEMPAC, PACIFIER, DEBELLUM and DEBATE-SFA in the superficial femoral artery.
He pointed out some of the limitations of these studies such as the small sizes of the cohorts (that make meaningful subgroup analysis not possible) and high drop-out rate seen in these trials. Katoh also stated that these trials included a heterogeneous patient population with respect to Rutherford classification, de novo and restenotic lesions, in-stent restenosis etc. “Other aspects to be considered were the short follow-up periods and the lack of patient-related endpoints,” he maintained.
Other limitations with the trials published so far include: no or insufficient blinding; no allocation concealment; dearth of information on intention-to-treat, per protocol and as-treated analysis, all of which result in the fact that published data in support of drug-eluting balloons are of low to moderate quality of evidence, Katoh told delegates.