In the Journals

No 5-year mortality signal in trial of PCB for below-the-knee lesions

Thomas Zeller

A paclitaxel-coated balloon was not associated with elevated mortality risk in patients who underwent revascularization for critical limb ischemia, according to 5-year data from the IN.PACT DEEP trial.

As Healio previously reported, at 1 year in IN.PACT DEEP, the paclitaxel-coated balloon (PCB; IN.PACT Amphirion, Medtronic) was noninferior to percutaneous transluminal angioplasty in efficacy, but was associated with a signal for major amputation. The PCB has since been discontinued.

For the present project, researchers analyzed freedom from clinically driven target lesion revascularization, amputation and all-cause death at 5 years in the trial population of 358 patients. A recent meta-analysis found a signal of lower rates of amputation-free survival at 1 year for PCB compared with PTA in patients with below-the-knee lesions, as Healio previously reported.

No safety signals

Thomas Zeller, MD, associate professor of angiology at Universitaets-Herzzentrum Freiburg, Bad Krozingen, Germany, and colleagues found no differences between the groups at 5 years in freedom from clinically driven TLR (PCB, 70.9%; PTA, 76%; log-rank P = .406) or in incidence of the safety composite endpoint of clinically driven TLR/major amputation/all-cause death (PCB, 59.8%; PTA, 57.5%; log-rank P = .309).

Major amputation occurred in 15.4% of the PCB group compared with 10.6% of the PTA group (log-rank P = .108), according to the researchers.

All-cause mortality rates did not differ between the groups at 5 years (PCB, 39.4%; PTA, 44.9%; log-rank P = .727), Zeller and colleagues wrote.

Independent predictors of mortality at 5 years included age (HR = 1.04; 95% CI, 1.02-1.07), Rutherford category of 5 or 6 (HR = 2.7; 95% CI, 1.45-5) and previous peripheral revascularization (HR = 1.53; 95% CI, 1.05-2.23), but not tertile of paclitaxel dosage, according to the researchers.

New research needed

“The paclitaxel-coated IN.PACT Amphirion DCB was not efficient in terms of reducing restenosis and TLR rates compared with PTA,” Zeller and colleagues wrote. “However, in the long term, no statistically significantly increased amputation or all-cause mortality rates were found. Further studies using more effective drug coatings in this challenging patient population are warranted.”

In a related editorial, Jos C. van den Berg, MD, PhD, head of the interventional radiology service at Centro Vascolare Ticino, Ospedale Regionale di Lugano, Sede Civico, Lugano Switzerland, wrote: “Given the small number of patients in the control group and the important number of patients who were lost to follow-up, it is necessary to pool all patient-level data that have been published thus far and perform a new meta-analysis. ... When designing new prospective studies, it will be important to include mortality risk as one of the endpoints, even when this would mean that thousands of patients must be enrolled.” – by Erik Swain

Disclosures: The analysis was funded by Medtronic. Zeller reports he has financial ties with 480 Biomedical, Abbott Vascular, Bard Peripheral Vascular, Bayer, B. Braun, Biotronik, Boston Scientific, Cook Medical, Intact Vascular, Med Alliance, Medtronic, Philips/Spectranetics, QT Medical, Shockwave, Terumo, TriReme, Veryan and W.L. Gore & Associates. Please see the study for all other authors’ relevant financial disclosures. Van den Berg reports no relevant financial disclosures.

Thomas Zeller

A paclitaxel-coated balloon was not associated with elevated mortality risk in patients who underwent revascularization for critical limb ischemia, according to 5-year data from the IN.PACT DEEP trial.

As Healio previously reported, at 1 year in IN.PACT DEEP, the paclitaxel-coated balloon (PCB; IN.PACT Amphirion, Medtronic) was noninferior to percutaneous transluminal angioplasty in efficacy, but was associated with a signal for major amputation. The PCB has since been discontinued.

For the present project, researchers analyzed freedom from clinically driven target lesion revascularization, amputation and all-cause death at 5 years in the trial population of 358 patients. A recent meta-analysis found a signal of lower rates of amputation-free survival at 1 year for PCB compared with PTA in patients with below-the-knee lesions, as Healio previously reported.

No safety signals

Thomas Zeller, MD, associate professor of angiology at Universitaets-Herzzentrum Freiburg, Bad Krozingen, Germany, and colleagues found no differences between the groups at 5 years in freedom from clinically driven TLR (PCB, 70.9%; PTA, 76%; log-rank P = .406) or in incidence of the safety composite endpoint of clinically driven TLR/major amputation/all-cause death (PCB, 59.8%; PTA, 57.5%; log-rank P = .309).

Major amputation occurred in 15.4% of the PCB group compared with 10.6% of the PTA group (log-rank P = .108), according to the researchers.

All-cause mortality rates did not differ between the groups at 5 years (PCB, 39.4%; PTA, 44.9%; log-rank P = .727), Zeller and colleagues wrote.

Independent predictors of mortality at 5 years included age (HR = 1.04; 95% CI, 1.02-1.07), Rutherford category of 5 or 6 (HR = 2.7; 95% CI, 1.45-5) and previous peripheral revascularization (HR = 1.53; 95% CI, 1.05-2.23), but not tertile of paclitaxel dosage, according to the researchers.

New research needed

“The paclitaxel-coated IN.PACT Amphirion DCB was not efficient in terms of reducing restenosis and TLR rates compared with PTA,” Zeller and colleagues wrote. “However, in the long term, no statistically significantly increased amputation or all-cause mortality rates were found. Further studies using more effective drug coatings in this challenging patient population are warranted.”

In a related editorial, Jos C. van den Berg, MD, PhD, head of the interventional radiology service at Centro Vascolare Ticino, Ospedale Regionale di Lugano, Sede Civico, Lugano Switzerland, wrote: “Given the small number of patients in the control group and the important number of patients who were lost to follow-up, it is necessary to pool all patient-level data that have been published thus far and perform a new meta-analysis. ... When designing new prospective studies, it will be important to include mortality risk as one of the endpoints, even when this would mean that thousands of patients must be enrolled.” – by Erik Swain

Disclosures: The analysis was funded by Medtronic. Zeller reports he has financial ties with 480 Biomedical, Abbott Vascular, Bard Peripheral Vascular, Bayer, B. Braun, Biotronik, Boston Scientific, Cook Medical, Intact Vascular, Med Alliance, Medtronic, Philips/Spectranetics, QT Medical, Shockwave, Terumo, TriReme, Veryan and W.L. Gore & Associates. Please see the study for all other authors’ relevant financial disclosures. Van den Berg reports no relevant financial disclosures.