Author + information
- Michael R. Jaff, DO∗ ()
- ↵∗Reprint requests and correspondence:
Dr. Michael R. Jaff, Massachusetts General Hospital, 55 Fruit Street, Warren 905, Boston, Massachusetts 02114.
With the overwhelming expansion of diabetes mellitus across the world (1), it is of no surprise that peripheral artery disease (PAD) is now a worldwide health hazard (2). With improved diagnostic methods and increasing awareness, more patients are being considered for revascularization strategies. Classically, revascularization in the form of surgical bypass was reserved for patients with manifestations of critical limb ischemia (rest pain, nonhealing ischemic ulcerations, gangrene). With the rapid advances in minimally invasive technologies over the past 2 decades, “endovascular first” strategies have become prevalent. As one observes the evolution of devices from uncoated percutaneous transluminal angioplasty (3), bare nitinol stents (4), atherectomy (5), to drug-eluting stents (6), optimism for our ability to improve functional limitations and reduce the risk of limb loss has increased.
The ability to coat a balloon angioplasty catheter with an antiproliferative agent, however, has resulted in tremendous anticipation and enthusiasm by investigators and clinicians alike as a potential primary management of femoropopliteal PAD. This was sparked by the initial publication of the THUNDER (Local Taxan With Short Time Contact for Reduction of Restenosis in Distal Arteries) trial (7). In this pilot randomized trial, the primary endpoint of late lumen loss (a measure adopted from percutaneous coronary intervention trials) favored the balloon catheter coated with a concentrated film of paclitaxel. In this issue of JACC: Cardiovascular Interventions, the investigators extend the experience from the THUNDER trial by reporting 5-year outcomes (8). The authors, who represent some of the most important and influential PAD investigators worldwide, continue to expand our knowledge of the role of interventional management in patients with symptomatic PAD.
Only 2 of the 3 previously randomized arms in the THUNDER trial were included in this analysis, representing 102 patients. Unfortunately, this follow-up was not always performed with an in-person evaluation, but rather via telephone assessments. This immediately limits our ability to generalize these results to larger patient cohorts. In addition, formal anatomic follow-up was not mandated in all patients at 5 years, and therefore, only those patients who actually had arteriography and/or duplex ultrasonography and could actually obtain those images were analyzed. Independent core laboratories did not interpret these images.
The authors do a commendable job of demonstrating the consistent advantages of the drug-coated balloon to bare balloon angioplasty, including a reduction in late lumen loss, fewer target lesion revascularizations (TLR), longer time periods from the initial intervention to TLR, and despite the small numbers and limitations of the analysis, improved binary patency at 5 years. These impressive findings were associated with no increase in adverse events, including arterial toxicity, amputations, or mortality rates.
The combination of devices and drugs for the management of PAD appears to hold considerable appeal for clinicians, researchers, and commercial manufacturers alike (9). Although the results of drug-eluting stents are superior to percutaneous transluminal angioplasty (6), there remain concerns about permanent implantable devices. Bioresorbable scaffolds hold tremendous hope (10); however, at least in the peripheral artery segments, no large-scale trials are near completion, and the early results are awaiting peer-reviewed publication.
Drug-coated balloons, however, have been widely available in Europe, and the first trial data presented to a U.S. Food and Drug Administration panel was completed earlier this summer (11). Another large-scale randomized trial presented its data at an international meeting in April 2014 (12). It is therefore anticipated that drug-coated balloons will enter the U.S. marketplace within the next 12 to 18 months.
The enthusiasm for drug-coated balloons rests with the lack of a permanent implantable device, an antiproliferative agent to lessen restenosis, and the ability to offer a full spectrum of revascularization strategies should the initial intervention fail. With the recently reported randomized data (still pending peer-reviewed publication at the time this paper was written) and the results of the THUNDER 5-year follow-up, it appears that drug-coated balloons will have an impact on the patients with PAD who require intervention. One factor that will undoubtedly impact the uptake of this class of technologies is the cost effectiveness compared with other revascularization and medical strategies. The data on this are quite limited but suggest a potential advantage to payers because of the low TLR rates of drug-coated balloons (13).
The 5-year THUNDER trial data unfortunately do not shed light on the actual cost impact of the 2 arms reported. In addition, we have no insights into the optimal drug, the optimal dose concentration of the drug, effective adjuvant medical therapy, including the role of antiplatelet therapy, cholesterol lowering, and tobacco cessation. Finally, there remain no comparisons of drug-coated balloons for treatment of claudication as a result of femoropopliteal artery disease to supervised exercise and optimal medical therapy, as studied in iliac artery disease (14).
Are there lessons here? Undoubtedly. We need to determine what endpoints for trials in patients with claudication truly matter, and to which constituency. Each trial must demonstrate objective functional benefits following intervention, as that is why patients want these procedures—they choose to walk farther with less discomfort. We are obligated, in this era of accountable care, to measure episodes of care and total medical expense, and consider comparative costs and outcomes. We need to consider what is really cost effective for the claudicant (15). If we don’t, I am afraid that the THUNDER we hear will not represent advancing data but rather, doors closing to adoption of new technologies and outcomes by payers, ultimately limiting options for our PAD patients.
↵∗ Editorials published in JACC: Cardiovascular Interventions reflect the views of the authors and do not necessarily represent the views of JACC: Cardiovascular Interventions or the American College of Cardiology.
Dr. Jaff is a noncompensated advisor to Abbott Vascular, Boston Scientific, Cordis, Covidien Vascular, Medtronic Vascular; a paid consultant to Cardinal Health; an equity shareholder of PQ Bypass; and a board member of VIVA Physicians, a 501 c 3 not-for-profit education and research organization.
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