Durable Clinical Effectiveness With Paclitaxel-Eluting Stents in the Femoropopliteal Artery: 5-Year Results of the Zilver PTX Randomized Trial

Abstract

Background: This randomized controlled trial evaluated clinical durability of Zilver PTX, a paclitaxel-coated drug-eluting stent (DES), for femoropopliteal artery lesions. Outcomes compare primary DES versus percutaneous transluminal angioplasty (PTA), overall DES (primary and provisional) versus standard care (PTA and provisional Zilver bare metal stent [BMS]), and provisional DES versus provisional BMS.

Methods and results: Patients with symptomatic femoropopliteal artery disease were randomly assigned to DES (n=236) or PTA (n=238). Approximately 91% had claudication; 9% had critical limb ischemia. Patients experiencing acute PTA failure underwent secondary randomization to provisional BMS (n=59) or DES (n=61). The 1-year primary end points of event-free survival and patency showed superiority of primary DES in comparison with PTA; these results were sustained through 5 years. Clinical benefit (freedom from persistent or worsening symptoms of ischemia; 79.8% versus 59.3%, P<0.01), patency (66.4% versus 43.4%, P<0.01), and freedom from reintervention (target lesion revascularization, 83.1% versus 67.6%, P<0.01) for the overall DES group were superior to standard care in nonrandomized comparisons. Similarly, clinical benefit (81.8% versus 63.8%, P=0.02), patency (72.4% versus 53.0%, P=0.03), and freedom from target lesion revascularization (84.9% versus 71.6%, P=0.06) with provisional DES were improved over provisional BMS. These results represent >40% relative risk reduction for restenosis and target lesion revascularization through 5 years for the overall DES in comparison with standard care and for provisional DES in comparison with provisional BMS.

Conclusions: The 5-year results from this large study provide long-term information previously unavailable regarding endovascular treatment of femoropopliteal artery disease. The Zilver PTX DES provided sustained safety and clinical durability in comparison with standard endovascular treatments.

Clinical trial registration: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00120406.

Keywords: angioplasty; drug-eluting stents; paclitaxel; peripheral artery disease; stents.

Figure 1.

Patient flow diagram. Enrollment by original random assignment, death (all-cause), withdrawal, and loss to follow-up through 5 years are shown. BMS indicates bare metal stent; DES, drug-eluting stent; and PTA, percutaneous transluminal angioplasty.

Figure 2.

Five-year freedom from TLR outcomes comparing overall DES (primary DES + provisional DES) with standard care (provisional BMS placement + optimal PTA). The black curve shows 67.6% freedom from TLR for the standard care group, and the red curve shows the significantly higher (P<0.01) 83.1% freedom from TLR rate for the DES group. The life table is included. BMS indicates bare metal stent; DES, drug-eluting stent; PTA, percutaneous transluminal angioplasty; and TLR, target lesion revascularization.

Figure 3.

Five-year primary patency outcomes comparing overall DES (primary DES + provisional DES) to standard care (provisional BMS placement + optimal PTA). The black curve shows 43.4% primary patency for the standard care group, and the red curve shows the significantly higher (P<0.01) 66.4% primary patency rate for the DES group. The life table is included. BMS indicates bare metal stent; DES, drug-eluting stent; and PTA, percutaneous transluminal angioplasty.

Figure 4.

Restenosis hazard ratio for overall DES in comparison with standard care among subgroups of interest through 5 years. The diamonds indicate the hazard ratios, and the lines indicate the 95% confidence intervals (CIs). DES indicates drug-eluting stent.

Figure 5.

Five-year freedom from TLR outcomes comparing provisional DES with provisional BMS. The black curve shows 71.6% freedom from TLR for the provisional BMS group, and the red curve shows the 84.9% freedom from TLR rate for the provisional DES group. The life table is included. BMS indicates bare metal stent; DES, drug-eluting stent; and TLR, target lesion revascularization.

Figure 6.

Five-year primary patency outcomes comparing provisional DES with provisional BMS. The black curve shows 53.0% primary patency for the provisional BMS group, and the red curve shows the significantly higher (P=0.03) 72.4% primary patency rate for the provisional DES group. The life table is included. BMS indicates bare metal stent; and DES, drug-eluting stent.

Figure 7.

Five-year posttreatment clinical benefit outcomes comparing overall DES (primary DES + provisional DES) with standard care (provisional BMS placement + optimal PTA). Clinical benefit was defined as freedom from persistent or worsening claudication, rest pain, ulcer, or tissue loss after the initial study treatment. The black curve shows that 59.3% of patients in the standard care group maintained clinical benefit, and the red curve shows that 79.8% of patients in the DES group maintained clinical benefit (P<0.01). The life table is included. BMS indicates bare metal stent; DES, drug-eluting stent; and PTA, percutaneous transluminal angioplasty.

Figure 8.

Five-year posttreatment clinical benefit outcomes comparing provisional DES with provisional BMS. Clinical benefit was defined as freedom from persistent or worsening claudication, rest pain, ulcer, or tissue loss after the initial study treatment. The black curve shows that 63.8% of patients in the provisional BMS group maintained clinical benefit, and the red curve shows that 81.8% of patients in the provisional DES group maintained clinical benefit (P=0.02). The life table is included. BMS indicates bare metal stent; and DES, drug-eluting stent.