Data on one paclitaxel-coated balloon (DCB) failed to support suspicions that such devices cause harm when used for peripheral artery disease (PAD), researchers found from a meta-analysis.
Clinical trial participants who received the IN.PACT Admiral from Medtronic had a 9.3% rate of all-cause mortality within 5 years, similar to the 11.2% among peers who got uncoated percutaneous transluminal angioplasty (PTA; P=0.399), according to a group led by Peter Schneider, MD, of Hawaii Permanente Medical Group and Kaiser Foundation Hospital in Honolulu.
And none of the deaths, which were adjudicated by an independent clinical events committee, were considered device-related, the researchers reported in the Journal of the American College of Cardiology.
Dividing the DCB cohort by paclitaxel dose (averaging 5.2 mg, 10.0 mg, and 20.0 mg from low to high terciles), the investigators also saw no difference in mortality rates among these groups (P=0.700).
“This independent patient-level meta-analysis demonstrates that paclitaxel DCBs are safe. There is no correlation between any level of paclitaxel exposure and mortality,” Schneider and colleagues concluded. The findings were also recently presented at the Leipzig Interventional Course.
A composite of all-cause mortality, major target limb amputation, clinically-driven target vessel revascularization, and thrombosis yielded an advantage to DCB recipients (35.2% vs 45.4% for PTA, P=0.036).
“Differences in post-index procedure care may have played a role in mortality and urgently requires further investigation,” Schneider’s group suggested. They cautioned, though, that their meta-analysis suffered from lack of blinding in the included studies and a small number of PTA patients.
The meta-analysis used patient-level data from four studies of DCBs (n=1,837) and PTA (n=143) use: randomized trials IN.PACT SFA and IN.PACT SFA Japan, and the single-arm studies IN.PACT SFA China and IN.PACT Global.
“These four studies comprise the largest, most complete, and fully-adjudicated database of longitudinally-followed DCB patients to date. This provides added statistical power to evaluate whether paclitaxel played a role in mortality and whether paclitaxel dose had an impact on safety, though there is patient and lesion heterogeneity across studies,” the authors said.
Their conclusions appear to contradict those of another meta-analysis in December.
Back then, researchers showed an uptick in 5-year mortality among those receiving paclitaxel-eluting DCBs and drug-eluting stents for femoropopliteal artery disease.
“Due to the broad variety of lesion subsets and devices used in these trials, and the small sample size, the only way to properly evaluate the safety and efficacy outcomes in these trials is by using patient-level data. I think that actually combining trials using different devices and patients with different comorbid conditions (especially when sample size is small and groups not properly balanced) is very dangerous,” said Juan Granada, MD, president and CEO of the Cardiovascular Research Foundation in New York City.
“The bottom line is that we really need to link the science with the outcomes, and if you actually look at dosing and tissue distribution … I don’t really think that there is a scientific explanation for a difference in mortality at 5 years with the data that we have right now,” Granada told MedPage Today.
The FDA recently announced that it is investigating the safety of these devices.
“Additional patient-level analyses are underway by the FDA, independent physicians, and industry, and SCAI [Society for Cardiovascular Angiography and Interventions] is closely monitoring this evolving situation,” the society commented in a press release.
“At present, SCAI concurs with the FDA that the benefits of paclitaxel devices continue to outweigh any potential risks. However, we strongly encourage our members to discuss the findings of the [December] meta-analysis with their patients and to report any safety concerns to the FDA,” SCAI President David Cox, MD, said in the statement.
Granada said he is part of a group now seeking to design a study powered to confirm or refute a DCB mortality signal.
“We’re working hard on trying to figure out if these findings are real. The issue is that none of the studies included in these meta-analysis were designed to find differences in mortality. It has been discussed that a study designed to answer this question would require between 4,000 to 6,000 patients, something that will be difficult to achieve in the near term,” according to him.
Medtronic funded the study.
Schneider reported being on the advisory board for Medtronic, Abbott, and Boston Scientific; and consulting for Surmodics, Silk Road Medical, Medtronic, Cardinal, CSI, and Profusa. He is a Chief Medical Officer for Intact Vascular and Cagent.