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Paclitaxel-coated balloon not tied to mortality in patient-level analysis
In a patient-level meta-analysis of the IN.PACT studies, a paclitaxel-coated balloon was not associated with elevated risk for mortality, according to data presented at the Leipzig Interventional Course.
As Cardiology Today’s Intervention previously reported, a summary-level meta-analysis published in the Journal of the American Heart Association indicated that patients with peripheral artery disease who received paclitaxel-coated devices had elevated risk for mortality at 2 and 5 years compared with patients in control arms. After the publication, two trials of paclitaxel-coated devices temporarily halted enrollment pending further review and the FDA announced it would conduct its own investigation.
The news also prompted researchers to conduct the patient-level meta-analysis from four studies of the paclitaxel-coated balloon (IN.PACT Admiral, Medtronic) — IN.PACT SFA I and II and IN.PACT Japan, which were randomized controlled trials; and IN.PACT Global and IN.PACT China, which were single-arm studies — presenter Peter Schneider, MD, vascular surgeon and chief of the vascular therapy division at Kaiser Foundation Hospital, Honolulu, told Cardiology Today’s Intervention.
“We owe it to the patients and ourselves that whenever there is an issue like this, we consider it an urgent matter until it’s resolved,” Schneider said in an interview. “It is such an important commitment to do no harm and to only offer patients treatments that we truly believe in and that we think are going to dramatically improve their lives.”
Included in the studies were 1,837 patients treated with the paclitaxel-coated balloon (mean age, 69 years; 68% men) and 143 patients treated with percutaneous transluminal angioplasty (mean age, 69 years; 71% men). The researchers reviewed baseline, procedure and follow-up data of all individual patients, compared mortality rates between treatment groups, assessed whether there was a relationship between paclitaxel dose and mortality and tested for alternative hypotheses. All events were adjudicated by a clinical events committee.
Unlike the JAHA meta-analysis, the current study included raw patient-level data, including calculation of paclitaxel doses, and included complete data sets with longer-term data, Schneider said.
“This was a perfect set of raw data upon which to test the hypothesis” generated by the JAHA meta-analysis, he said in an interview. “Patient-level data are vastly different from summary-level data. With summary-level data, you have to make certain assumptions about how much paclitaxel the patient received and about what happened with censored patients and patients who were lost to follow-up. With patient-level data, you can actually calculate the paclitaxel dose and read dedicated summaries for each patient to understand what happened to them. This also affords you the opportunity to look at multiple different variables associated with safety and efficacy issues.”
Schneider noted that compared with the PTA group, the paclitaxel-coated balloon group had more in-stent restenosis, had longer lesions, were more likely to have calcified lesions and occluded lesions and more often needed a provisional stent.
Nonetheless, he said, at 5 years, there was no significant difference between the groups in all-cause mortality (paclitaxel-coated balloon, 9.3%; PTA, 11.2%).
The researchers also found there was no significant difference in mean nominal dose of paclitaxel between patients who died and patients who did not.
When patients were stratified into tertiles by paclitaxel dose, there was no significant difference in freedom from 5-year mortality between the groups (highest dose, 91.7%; middle dose, 90%; lowest dose, 90.6%).
According to the researchers, predictors of 5-year mortality included older age (adjusted HR = 1.051; 95% CI, 1.031-1.072), renal insufficiency (aHR = 2.205; 95% CI, 1.446-3.363), previous target limb amputation (aHR = 3.418; 95% CI, 1.542-7.58) and higher Rutherford category (aHR = 1.793; 95% CI, 1,156-2.781).
“What I see is not suggesting to me that there is a safety issue or a mortality issue,” Schneider told Cardiology Today’s Intervention. “But when an issue of this nature comes up, we need to be secure about whatever conclusion we come to.”
In the paclitaxel-coated balloon group, compared with those who died, those who survived had a higher compliance rate, meaning the number of completed visits was equal to or greater than the number of expected visits (88.3% vs. 82.9%; P < .001), which Schneider said may suggest an alternative hypothesis.
“The FDA is currently saying the benefits outweigh the risks, but they are on guard for any new information,” Schneider said in an interview. “This patient-level data is currently the only really new information, and if anything, it gives me more confidence to include paclitaxel-containing devices in my algorithm for patient treatment, especially since the efficacy is such an improvement compared with purely mechanical treatments.”
The study will be published in the Journal of the American College of Cardiology, Schneider said.
“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,” Mark Pacyna, vice president and general manager of the peripheral business for Medtronic, said in a press release. “The evidence presented today at [Leipzig Interventional Course] underscores our ongoing commitment to patient safety, improved long-term outcomes and data transparency.” – by Erik Swain
Reference:
Schneider P, et al. Long-term safety of drug-eluting technologies in the leg — recent findings, controversies, and future outlook. Presented at: Leipzig Interventional Course; Jan. 22-25, 2019; Leipzig, Germany.
Disclosure: The IN.PACT studies were funded by Medtronic, but the patient-level meta-analysis was not. Schneider reports he serves on scientific advisory boards for Abbott, Boston Scientific and Medtronic, consults for Cardinal Health, Cardiovascular Systems Inc., Medtronic, Profusa, Silk Road Medical and Surmodics, and serves as chief medical officer for Cagent and Intact Vascular.