Medtronic hopes newly presented five-year survival data put to rest any concerns about the long-term safety of the company’s IN.PACT Admiral drug-coated balloon (DCB).
Paclitaxel-coated balloons and stents—used to treat patients with femoropopliteal artery disease—have come under scrutiny since a meta-analysis published in December concluded the devices were associated with significantly increased mortality rates at two and five years post-implantation. Specifically, that analysis of 28 randomized controlled trials found all-cause death rates were 7.2 percent at two years for the drug-eluting or drug-coated devices and 3.8 percent in a control group treated with uncoated balloons or bare-metal stents. At five years, the corresponding mortality rates were 14.7 percent and 8.1 percent.
After those results were published, two trials designed to evaluate drug-coated devices for patients with peripheral artery disease (PAD) were paused, and the FDA announced it was going to investigate the signal of increased late mortality associated with paclitaxel-coated devices.
But data presented Jan. 22 at the Leipzig Interventional Course (LINC) in Leipzig, Germany, suggest those poor outcomes don’t apply to the IN.PACT Admiral. Vascular surgeon Peter Schneider, MD, who served as principal investigator in a U.S. trial of the device, presented patient-level results from 1,837 people treated with the DCB in relation to patients treated with plain balloon angioplasty (PTA).
That analysis incorporated four different studies including IN.PACT SFA, IN.PACT SFA Japan, IN.PACT SFA China and IN.PACT Global. Key results were as follows:
- There was no statistically significant difference in all-cause mortality at five years between those treated with the paclitaxel-coated device (9.3 percent) versus PTA (11.2 percent).
- Paclitaxel dose wasn’t significantly correlated to long-term survival. When DCB patients were broken into three groups based on the paclitaxel dose delivered, Kaplan-Meier estimates calculated freedom from all-cause mortality at 91.7 percent for the upper dose range, 90.6 percent for the middle range and 90 percent for the lower range.
- The 140 patients who died during follow-up averaged similar nominal doses of paclitaxel to the 1,696 who survived.
"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,” Schneider, a member of Medtronic’s scientific advisory board, said in a press release.
The analysis was independently performed by the Baim Institute for Clinical Research and led by Gheorghe Doros, PhD, who said the individual patient data meta-analysis was a more appropriate measure of safety for the particular device than the aggregate data meta-analysis that raised the mortality concerns.
"The advantages are realized by being able to utilize 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,” Doros said.
Three-year data from the IN.PACT SFA Japan study were also presented. That study found a lower mortality rate in the 68 patients randomized to DCB treatment (6.0 percent) compared to the 32 who were treated with PTA (6.9 percent).
Primary patency was also higher in the DCB group (68.9 percent versus 46.9 percent) based on three-year Kaplan-Meier estimates, and so was freedom from clinically driven target lesion revascularization (84.4 percent versus 81.3 percent).
"In light of recent discussions around the safety of paclitaxel-coated and -eluting technologies, it's now more important than ever for Medtronic and our industry peers to be forthcoming with all our clinical data," said Mark Pacyna, vice president and general manager of Medtronic’s Peripheral business. "The evidence presented today at LINC underscores our ongoing commitment to patient safety, improved long-term outcomes, and data transparency."