Paclitaxel-Eluting Stent Shines for Peripheral Artery Disease

WASHINGTON – Treating symptomatic femoropopliteal artery disease with a paclitaxel-eluting peripheral stent beat both percutaneous transluminal angioplasty and provisional bare-metal stenting in achieving vessel patency rates at 12 months in a prospective, randomized trial.

With the increasing development of dedicated devices for peripheral lesions, more interventional cardiologists have become interested in peripheral interventions. Other drug-eluting stents that were tested in previous trials failed, however, to show significant differences in outcome, compared with those of bare-metal stenting.

This trial was different. In one major finding of the multitiered study, patency rates at 12 months were 83.1% with Cook Medical Inc.’s paclitaxel-eluting Zilver stent and 67% with “standard” care (angioplasty with provisional bare-metal stenting). And in a head-to-head comparison of provisional stenting, the patency rate was 89.9% with the Zilver PTX stent and 73% with the bare-metal stent.

“This is the largest randomized trial ever performed for the endovascular management of peripheral artery disease,” said principal investigator Dr. Michael D. Dake, who presented the results of the industry-sponsored Zilver PTX trial at the Transcatheter Cardiovascular Therapeutics 2010.

“I think it’s a signal that it’s possible to improve the results of current therapies for PAD with a combination of both drugs and mechanical devices,” he said in a press conference.

The trial enrolled 479 patients at 55 sites in the United States, Germany, and Japan. Patients had symptomatic disease of the above-the-knee femoropopliteal artery (most were moderately to severely symptomatic), as well as lesions up to 14 cm. The average lesion length was 6.6 cm, and vessel diameter was 4-9 mm.

In the first of two randomization protocols, patients were randomized to treatment with either conventional percutaneous transluminal angioplasty (PTA) or with the Zilver PTX stent, a self-expanding nitinol stent with a polymer-free paclitaxel coating. After 1 year, 83.1% of the vessels that were treated with the paclitaxel-eluting stent were still patent, compared with 32.8% of the vessels in the PTA-treated group.

Patency was defined as peak systolic velocity ratio less than 2.0 as measured by duplex ultrasonography, or diameter stenosis less than 50% as determined by angiography.

However, PTA failed to restore primary patency in approximately half of the patients in the PTA group – a rate seen in other trials. When the Zilver PTX stent was compared with “optimal” PTA (only those who achieved optimal results after primary PTA), the Zilver stent still performed significantly better, at 83.1% vs. 65.3%.

In the secondary randomization, the “suboptimal” PTA group (those who failed primary PTA) was randomized again to receive either a bare-metal Zilver stent or the paclitaxel-eluting version. In this comparison of provisional stenting, 12-month patency rates were 89.9% in the Zilver PTX group and 73% in the bare-metal stent group.

In other words, the 12-month restenosis rates were 10.1% with the Zilver PTX stent and 27% with the bare-metal stent, said Dr. Dake of Stanford (Calif.) University.

In another analysis crossing both tiers, the investigators compared primary use of the paclitaxel-eluting stent with the “real-world standard of care” in a group that comprised patients whose PTA treatment was optimal as well as those who received bare-metal stents after their PTA had failed. This “standard of care” group had a patency rate of 67%, significantly less than the 83.1% patency rate of the primary Zilver PTX group.

The primary safety end point was 12-month, event-free survival, which included freedom from amputation, target lesion revascularization, and significant worsening of claudication. Event-free survival was 90.4% in the patients who were initially randomized for treatment with the Zilver PTX stent and 82.6% in the PTA group.

There was “only a 0.9% stent fracture rate through 12 months,” and none of the four stent fractures that occurred had any clinical sequelae, said Dr. Dake.

Moreover, subgroup studies with intravascular ultrasound and angiography showed “no evidence of untoward effects [of the drug] or complications of the device,” and there were no cases of acute stent thrombosis, he reported. Patients in the trial were on a dual antiplatelet regimen for at least 2 months. At 12 months, “61% of patients had remained on it,” Dr. Dake said.

Dr. John Laird of the University of California, Davis, Medical Center said that longer-term results are critical since “there’s potential for late restenosis” resulting from the “chronic injury and chronic irritation” caused by stents. “The big difference here is that there’s no polymer on the stent to be a source of irritation as well,” he said.

It is also uncertain whether the patency results can be replicated with the longer lesions that are typically seen in PAD in the “real world,” panelists said.

(Investigators in the current randomized trial were limited, per the Food and Drug Administration–approved study protocol, to treat lesions that were no longer than 14 cm, Dr. Dake said.)

Dr. Hans Krankenberg of the cardiovascular center at the University of Hamburg (Germany) said that an ongoing international Zilver PTX registry is showing, thus far, that “the findings from this trial can be transferred to almost all [other lesions].”

Patients in the randomized trial had an average age of 68 years, and almost half had diabetes.

Clinical outcomes, which will be presented later, mirror the patency findings, Dr. Dake said. There will be ongoing follow-up through 5 years.

Dr. William A. Gray, director of endovascular services at Columbia University Medical Center, New York, who moderated a discussion of the study at the meeting, noted that the Zilver PTX trial followed both the SIROCCO trial, which tested a sirolimus-eluting, durable polymer–coated SMART stent against a bare-metal stent in patients with femoropopliteal disease, and the STRIDES trial, which tested an everolimus-eluting, durable polymer–coated ABSOLUTE stent. Both studies failed to show any real efficacy at reducing restenosis.

The Zilver PTX stent lacks a durable polymer and delivers paclitaxel rather than a limus drug, which raises questions about the causal mechanisms for its unprecedented success, Dr. Gray said. There are also questions about how its effectiveness in the shorter lesions in this trial can be extrapolated to real-world lesion lengths of 20 cm and even 30 cm. Nevertheless, he noted, this positive trial is a critically important proof of concept, and potentially groundbreaking in the way superficial femoral artery disease and popliteal treatment will be viewed from now on.

The Zilver PTX stent is currently available in Europe. In the United States, Cook Medical has submitted a premarket approval application to the FDA, a company spokesperson said.

The trial was sponsored by Cook Medical, which manufactures the Zilver PTX stent. Dr. Dake disclosed that he had clinical trial support from Cook Medical, consulting fees/honoraria from W.L. Gore and Abbott Vascular, and equity interest/stock options in various device companies. Dr. Gray is a consultant for Cook Medical, which manufactures the Zilver PTX stent, as well as Abbott Vascular and Cordis/Johnson and Johnson.

* Correction, Oct. 20, 2010: The original version of this article incorrectly referred to Zilver PTX as Zenith PTX on several references. This version has been updated. 

WASHINGTON – Treating symptomatic femoropopliteal artery disease with a paclitaxel-eluting peripheral stent beat both percutaneous transluminal angioplasty and provisional bare-metal stenting in achieving vessel patency rates at 12 months in a prospective, randomized trial.

With the increasing development of dedicated devices for peripheral lesions, more interventional cardiologists have become interested in peripheral interventions. Other drug-eluting stents that were tested in previous trials failed, however, to show significant differences in outcome, compared with those of bare-metal stenting.

This trial was different. In one major finding of the multitiered study, patency rates at 12 months were 83.1% with Cook Medical Inc.’s paclitaxel-eluting Zilver stent and 67% with “standard” care (angioplasty with provisional bare-metal stenting). And in a head-to-head comparison of provisional stenting, the patency rate was 89.9% with the Zilver PTX stent and 73% with the bare-metal stent.

“This is the largest randomized trial ever performed for the endovascular management of peripheral artery disease,” said principal investigator Dr. Michael D. Dake, who presented the results of the industry-sponsored Zilver PTX trial at the Transcatheter Cardiovascular Therapeutics 2010.

“I think it’s a signal that it’s possible to improve the results of current therapies for PAD with a combination of both drugs and mechanical devices,” he said in a press conference.

The trial enrolled 479 patients at 55 sites in the United States, Germany, and Japan. Patients had symptomatic disease of the above-the-knee femoropopliteal artery (most were moderately to severely symptomatic), as well as lesions up to 14 cm. The average lesion length was 6.6 cm, and vessel diameter was 4-9 mm.

In the first of two randomization protocols, patients were randomized to treatment with either conventional percutaneous transluminal angioplasty (PTA) or with the Zilver PTX stent, a self-expanding nitinol stent with a polymer-free paclitaxel coating. After 1 year, 83.1% of the vessels that were treated with the paclitaxel-eluting stent were still patent, compared with 32.8% of the vessels in the PTA-treated group.

Patency was defined as peak systolic velocity ratio less than 2.0 as measured by duplex ultrasonography, or diameter stenosis less than 50% as determined by angiography.

However, PTA failed to restore primary patency in approximately half of the patients in the PTA group – a rate seen in other trials. When the Zilver PTX stent was compared with “optimal” PTA (only those who achieved optimal results after primary PTA), the Zilver stent still performed significantly better, at 83.1% vs. 65.3%.

In the secondary randomization, the “suboptimal” PTA group (those who failed primary PTA) was randomized again to receive either a bare-metal Zilver stent or the paclitaxel-eluting version. In this comparison of provisional stenting, 12-month patency rates were 89.9% in the Zilver PTX group and 73% in the bare-metal stent group.

In other words, the 12-month restenosis rates were 10.1% with the Zilver PTX stent and 27% with the bare-metal stent, said Dr. Dake of Stanford (Calif.) University.

In another analysis crossing both tiers, the investigators compared primary use of the paclitaxel-eluting stent with the “real-world standard of care” in a group that comprised patients whose PTA treatment was optimal as well as those who received bare-metal stents after their PTA had failed. This “standard of care” group had a patency rate of 67%, significantly less than the 83.1% patency rate of the primary Zilver PTX group.

The primary safety end point was 12-month, event-free survival, which included freedom from amputation, target lesion revascularization, and significant worsening of claudication. Event-free survival was 90.4% in the patients who were initially randomized for treatment with the Zilver PTX stent and 82.6% in the PTA group.

There was “only a 0.9% stent fracture rate through 12 months,” and none of the four stent fractures that occurred had any clinical sequelae, said Dr. Dake.

Moreover, subgroup studies with intravascular ultrasound and angiography showed “no evidence of untoward effects [of the drug] or complications of the device,” and there were no cases of acute stent thrombosis, he reported. Patients in the trial were on a dual antiplatelet regimen for at least 2 months. At 12 months, “61% of patients had remained on it,” Dr. Dake said.

Dr. John Laird of the University of California, Davis, Medical Center said that longer-term results are critical since “there’s potential for late restenosis” resulting from the “chronic injury and chronic irritation” caused by stents. “The big difference here is that there’s no polymer on the stent to be a source of irritation as well,” he said.

It is also uncertain whether the patency results can be replicated with the longer lesions that are typically seen in PAD in the “real world,” panelists said.

(Investigators in the current randomized trial were limited, per the Food and Drug Administration–approved study protocol, to treat lesions that were no longer than 14 cm, Dr. Dake said.)

Dr. Hans Krankenberg of the cardiovascular center at the University of Hamburg (Germany) said that an ongoing international Zilver PTX registry is showing, thus far, that “the findings from this trial can be transferred to almost all [other lesions].”

Patients in the randomized trial had an average age of 68 years, and almost half had diabetes.

Clinical outcomes, which will be presented later, mirror the patency findings, Dr. Dake said. There will be ongoing follow-up through 5 years.

Dr. William A. Gray, director of endovascular services at Columbia University Medical Center, New York, who moderated a discussion of the study at the meeting, noted that the Zilver PTX trial followed both the SIROCCO trial, which tested a sirolimus-eluting, durable polymer–coated SMART stent against a bare-metal stent in patients with femoropopliteal disease, and the STRIDES trial, which tested an everolimus-eluting, durable polymer–coated ABSOLUTE stent. Both studies failed to show any real efficacy at reducing restenosis.

The Zilver PTX stent lacks a durable polymer and delivers paclitaxel rather than a limus drug, which raises questions about the causal mechanisms for its unprecedented success, Dr. Gray said. There are also questions about how its effectiveness in the shorter lesions in this trial can be extrapolated to real-world lesion lengths of 20 cm and even 30 cm. Nevertheless, he noted, this positive trial is a critically important proof of concept, and potentially groundbreaking in the way superficial femoral artery disease and popliteal treatment will be viewed from now on.

The Zilver PTX stent is currently available in Europe. In the United States, Cook Medical has submitted a premarket approval application to the FDA, a company spokesperson said.

The trial was sponsored by Cook Medical, which manufactures the Zilver PTX stent. Dr. Dake disclosed that he had clinical trial support from Cook Medical, consulting fees/honoraria from W.L. Gore and Abbott Vascular, and equity interest/stock options in various device companies. Dr. Gray is a consultant for Cook Medical, which manufactures the Zilver PTX stent, as well as Abbott Vascular and Cordis/Johnson and Johnson.

* Correction, Oct. 20, 2010: The original version of this article incorrectly referred to Zilver PTX as Zenith PTX on several references. This version has been updated. 

WASHINGTON – Treating symptomatic femoropopliteal artery disease with a paclitaxel-eluting peripheral stent beat both percutaneous transluminal angioplasty and provisional bare-metal stenting in achieving vessel patency rates at 12 months in a prospective, randomized trial.

With the increasing development of dedicated devices for peripheral lesions, more interventional cardiologists have become interested in peripheral interventions. Other drug-eluting stents that were tested in previous trials failed, however, to show significant differences in outcome, compared with those of bare-metal stenting.

This trial was different. In one major finding of the multitiered study, patency rates at 12 months were 83.1% with Cook Medical Inc.’s paclitaxel-eluting Zilver stent and 67% with “standard” care (angioplasty with provisional bare-metal stenting). And in a head-to-head comparison of provisional stenting, the patency rate was 89.9% with the Zilver PTX stent and 73% with the bare-metal stent.

“This is the largest randomized trial ever performed for the endovascular management of peripheral artery disease,” said principal investigator Dr. Michael D. Dake, who presented the results of the industry-sponsored Zilver PTX trial at the Transcatheter Cardiovascular Therapeutics 2010.

“I think it’s a signal that it’s possible to improve the results of current therapies for PAD with a combination of both drugs and mechanical devices,” he said in a press conference.

The trial enrolled 479 patients at 55 sites in the United States, Germany, and Japan. Patients had symptomatic disease of the above-the-knee femoropopliteal artery (most were moderately to severely symptomatic), as well as lesions up to 14 cm. The average lesion length was 6.6 cm, and vessel diameter was 4-9 mm.

In the first of two randomization protocols, patients were randomized to treatment with either conventional percutaneous transluminal angioplasty (PTA) or with the Zilver PTX stent, a self-expanding nitinol stent with a polymer-free paclitaxel coating. After 1 year, 83.1% of the vessels that were treated with the paclitaxel-eluting stent were still patent, compared with 32.8% of the vessels in the PTA-treated group.

Patency was defined as peak systolic velocity ratio less than 2.0 as measured by duplex ultrasonography, or diameter stenosis less than 50% as determined by angiography.

However, PTA failed to restore primary patency in approximately half of the patients in the PTA group – a rate seen in other trials. When the Zilver PTX stent was compared with “optimal” PTA (only those who achieved optimal results after primary PTA), the Zilver stent still performed significantly better, at 83.1% vs. 65.3%.

In the secondary randomization, the “suboptimal” PTA group (those who failed primary PTA) was randomized again to receive either a bare-metal Zilver stent or the paclitaxel-eluting version. In this comparison of provisional stenting, 12-month patency rates were 89.9% in the Zilver PTX group and 73% in the bare-metal stent group.

In other words, the 12-month restenosis rates were 10.1% with the Zilver PTX stent and 27% with the bare-metal stent, said Dr. Dake of Stanford (Calif.) University.

In another analysis crossing both tiers, the investigators compared primary use of the paclitaxel-eluting stent with the “real-world standard of care” in a group that comprised patients whose PTA treatment was optimal as well as those who received bare-metal stents after their PTA had failed. This “standard of care” group had a patency rate of 67%, significantly less than the 83.1% patency rate of the primary Zilver PTX group.

The primary safety end point was 12-month, event-free survival, which included freedom from amputation, target lesion revascularization, and significant worsening of claudication. Event-free survival was 90.4% in the patients who were initially randomized for treatment with the Zilver PTX stent and 82.6% in the PTA group.

There was “only a 0.9% stent fracture rate through 12 months,” and none of the four stent fractures that occurred had any clinical sequelae, said Dr. Dake.

Moreover, subgroup studies with intravascular ultrasound and angiography showed “no evidence of untoward effects [of the drug] or complications of the device,” and there were no cases of acute stent thrombosis, he reported. Patients in the trial were on a dual antiplatelet regimen for at least 2 months. At 12 months, “61% of patients had remained on it,” Dr. Dake said.

Dr. John Laird of the University of California, Davis, Medical Center said that longer-term results are critical since “there’s potential for late restenosis” resulting from the “chronic injury and chronic irritation” caused by stents. “The big difference here is that there’s no polymer on the stent to be a source of irritation as well,” he said.

It is also uncertain whether the patency results can be replicated with the longer lesions that are typically seen in PAD in the “real world,” panelists said.

(Investigators in the current randomized trial were limited, per the Food and Drug Administration–approved study protocol, to treat lesions that were no longer than 14 cm, Dr. Dake said.)

Dr. Hans Krankenberg of the cardiovascular center at the University of Hamburg (Germany) said that an ongoing international Zilver PTX registry is showing, thus far, that “the findings from this trial can be transferred to almost all [other lesions].”

Patients in the randomized trial had an average age of 68 years, and almost half had diabetes.

Clinical outcomes, which will be presented later, mirror the patency findings, Dr. Dake said. There will be ongoing follow-up through 5 years.

Dr. William A. Gray, director of endovascular services at Columbia University Medical Center, New York, who moderated a discussion of the study at the meeting, noted that the Zilver PTX trial followed both the SIROCCO trial, which tested a sirolimus-eluting, durable polymer–coated SMART stent against a bare-metal stent in patients with femoropopliteal disease, and the STRIDES trial, which tested an everolimus-eluting, durable polymer–coated ABSOLUTE stent. Both studies failed to show any real efficacy at reducing restenosis.

The Zilver PTX stent lacks a durable polymer and delivers paclitaxel rather than a limus drug, which raises questions about the causal mechanisms for its unprecedented success, Dr. Gray said. There are also questions about how its effectiveness in the shorter lesions in this trial can be extrapolated to real-world lesion lengths of 20 cm and even 30 cm. Nevertheless, he noted, this positive trial is a critically important proof of concept, and potentially groundbreaking in the way superficial femoral artery disease and popliteal treatment will be viewed from now on.

The Zilver PTX stent is currently available in Europe. In the United States, Cook Medical has submitted a premarket approval application to the FDA, a company spokesperson said.

The trial was sponsored by Cook Medical, which manufactures the Zilver PTX stent. Dr. Dake disclosed that he had clinical trial support from Cook Medical, consulting fees/honoraria from W.L. Gore and Abbott Vascular, and equity interest/stock options in various device companies. Dr. Gray is a consultant for Cook Medical, which manufactures the Zilver PTX stent, as well as Abbott Vascular and Cordis/Johnson and Johnson.

* Correction, Oct. 20, 2010: The original version of this article incorrectly referred to Zilver PTX as Zenith PTX on several references. This version has been updated.