New data on the IN.PACT Admiral drug-coated balloon (DCB; Medtronic) in patients with peripheral arterial disease (PAD) in the superficial femoral (SFA) and popliteal arteries finds no statistically significant difference in all-cause mortality when the DCB or plain balloon angioplasty (PTA) is used.
This is the headline result of the IN.PACT DCB paclitaxel safety analysis, an independent, patient-level survival analysis inclusive of all IN.PACT DCB clinical programmes, presented at the Leipzig Interventional Course (LINC) in Leipzig, Germany (22–255 January 2019) following clinical discussions around the safety of paclitaxel-coated and eluting technologies in the treatment of PAD. A Medtronic press release states that these data reiterate the company’s commitment to patient safety and data transparency.
A manuscript detailing outcomes from the IN.PACT DCB paclitaxel safety analysis was also accepted and is in press with the Journal of the American College of Cardiology (JACC).
Key data highlights include:
- At five years, there was no statistically significant difference in all-cause mortality between the DCB and PTA arms (9.3% vs. 11.2% respectively, p=0.399)
- Data found no correlation between paclitaxel dose and long-term survival. Patients treated in the DCB arm were classified by upper, mid, and lower dose ranges. Freedom from all-cause mortality based on Kaplan-Meier estimates was 91.7% in the upper range, 90.6% in the mid-range, and 90% in the lower range (p=0.700).
- Data demonstrated no difference in mean nominal dose of paclitaxel between overall survival in patients treated with DCB (n=1,696) and those who died (n=140). Mean nominal paclitaxel doses were 11,829.8μg±7,347.6μg and 11,419.6μg±7,414.8μg respectively (p=0.529).
Patient-level safety analysis
Peter Schneider, vascular surgeon at Kaiser Permanente Clinic in Honolulu, USA, presented data from the IN.PACT safety analysis at LINC. The independent, patient-level analysis evaluated the relationship between nominal dose of paclitaxel and mortality in all 1,837 DCB patients enrolled across the IN.PACT Admiral clinical programme, including IN.PACT SFA, IN.PACT SFA Japan, IN.PACT SFA China, and IN.PACT Global. The analysis was independently performed by the Baim Institute for Clinical Research (formerly the Harvard Clinical Research Institute) and led by Gheorghe Doros, professor of Biostatistics, Boston University School of Public Health and director, Statistical Consulting, Baim Institute of Clinical Research, Boston, USA.
“This independently adjudicated analysis includes 1,837 patients treated with IN.PACT Admiral and followed long-term,” explains Schneider. “In contrast to a recently published summary-level meta-analysis—which included 28 trials with different devices, designs, levels of monitoring, and follow-up periods—the findings from this study showed neither paclitaxel use, nor dose had any effect on mortality at five years.”
The analysis evaluated all-cause mortality across IN.PACT studies. This included device- or procedure-related death through five years and paclitaxel-related events through 12 months. Upon review of other endovascular therapies in published literature, it was found that the mortality rates across IN.PACT DCB studies are comparable to or lower than what would be expected in similar patient populations. Authors also found no significant difference between nominal dose in those with overall survival through five years. Furthermore, patients who died were older and shared a statistically higher level of co-morbidities at baseline, including coronary artery disease, diabetes, and chronic kidney disease, versus those with higher overall survival rates. Across all studies, results were reviewed and adjudicated by an independent clinical events committee.
“Individual patient data meta-analysis (IPD-MA) offers several advantages over the aggregate data meta-analysis (AD-MA) that renders it as a more powerful statistical approach, allowing for more thorough and more appropriate analyses,” comments Doros. “The advantages are realised by being able to utilise more accurate outcome data, such as time of event and time of drop-out, individual patient covariates, such as paclitaxel dose, patient comorbidities, as well as lesion and procedural characteristics, and more sophisticated statistical models, such as frailty Cox regression and inverse probability of treatment weighting (IPTW).”
“In light of recent discussions around the safety of paclitaxel-coated and -eluting technologies, it is now more important than ever for Medtronic and our industry peers to be forthcoming with all our clinical data,” says Mark Pacyna, vice president and general manager of the Peripheral business, which is part of the Aortic, Peripheral, and Venous division at Medtronic. “The evidence presented today at LINC underscores our ongoing commitment to patient safety, improved long-term outcomes, and data transparency.”
IN.PACT SFA Japan three-year results
New data from the IN.PACT SFA Japan study were also presented by Osamu Iida, of Kansai Rosai Hospital, Amagasaki, Japan. The data demonstrated continued safety, durability, and efficacy compared to PTA at three years. The study enrolled 100 patients across 11 sites in Japan and randomised treatment to either DCB (n=68) or PTA (n=32). Results showed a consistently low clinically-driven target lesion revascularisation (CD-TLR) rate and high patency rate.
IN.PACT SFA Japan demonstrated a 68.9% primary patency in the DCB group compared to 46.9% in the PTA group at three years based on Kaplan-Meier estimates (p=0.001). The three-year freedom from CD-TLR rates based on Kaplan-Meier estimates were 84.4% in the DCB group compared to 81.3% in the PTA group (p=0.451). In IN.PACT SFA Japan, major adverse events were also lower in the DCB group at three years with a rate of 20.9% compared to 31% in the PTA group (p=0.306), with no major target limb amputations in either study arm. The mortality rate was also lower in the DCB arm at 6%, versus 6.9% in the PTA group.
“We stand behind IN.PACT Admiral DCB, which is well supported by evidence from our robust clinical programme,” says Simona Zannetti, vice president, Clinical Research, Medical Affairs, and Education, Medtronic Aortic, Peripheral, and Venous. “In line with our commitment to timely data dissemination—and the physicians and patients we serve—it is critical that we continue to review, report, and publish our findings.”
