Author + information
- Received January 7, 2019
- Revision received January 16, 2019
- Accepted January 18, 2019
- Published online May 20, 2019.
- Peter A. Schneider, MDa,∗ (, )
- John R. Laird, MDb,
- Gheorghe Doros, PhDc,d,
- Qi Gao, MSc,
- Gary Ansel, MDe,
- Marianne Brodmann, MDf,
- Antonio Micari, MD, PhDg,
- Mehdi H. Shishehbor, DO, MPH, PhDh,
- Gunnar Tepe, MDi and
- Thomas Zeller, MD, PhDj
- aDivision of Vascular and Endovascular Surgery, University of California at San Francisco, San Francisco, California
- bAdventist Heart and Vascular Institute, St. Helena, California
- cBaim Institute for Clinical Research, Boston, Massachusetts
- dSchool of Public Health, Boston University, Boston, Massachusetts
- eOhio Health, Riverside Methodist Hospital, Columbus, Ohio
- fDivision of Angiology, Medical University Graz, Graz, Austria
- gHumanitas Gavazzeni Hospital, Bergamo, Italy
- hHeart & Vascular Institute, University Hospitals Cleveland Medical Center, and Case Western Reserve University School of Medicine, Cleveland, Ohio
- iRoMed Clinic, Rosenheim, Germany
- jUniversitäts-Herzzentrum Freiburg–Bad Krozingen, Bad Krozingen, Germany
- ↵∗Address for correspondence:
Dr. Peter A. Schneider, Division of Vascular and Endovascular Surgery, University of California at San Francisco, 400 Parnassus Avenue, Suite A-501, San Francisco, California 94143.
Background Five years of prospective clinical trials confirm that the paclitaxel drug-coated balloon (DCB) (IN.PACT Admiral, Medtronic, Dublin, Ireland) is safe and effective to treat femoropopliteal artery disease. A recent meta-analysis of heterogeneous trials of paclitaxel-based balloons and stents reported that they are associated with increased mortality and that higher doses are linked to higher mortality from 2 to 5 years.
Objectives The purpose of this study was to determine if there is a correlation between paclitaxel exposure and mortality by conducting an independent patient-level meta-analysis of 1,980 patients with up to 5-year follow-up.
Methods Data from 2 single-arm and 2 randomized independently adjudicated prospective studies of a paclitaxel DCB (n = 1,837) and uncoated percutaneous transluminal angioplasty (PTA) (n = 143) were included. Analyses of baseline, procedure, and follow-up data of individual patients were performed to explore correlations of paclitaxel dose with long-term mortality. Survival time by paclitaxel dose tercile was analyzed with adjustment of inverse probability weighting to correct baseline imbalances and study as random effect. A standard cohort was defined to compare DCB- and PTA-treated patients with similar characteristics by applying criteria from pivotal studies (n = 712 DCB, n = 143 PTA).
Results A survival analysis stratified nominal paclitaxel dose by low, mid, and upper terciles; mean doses were 5,019.0, 10,007.5, and 19,978.2 μg, respectively. Rates of freedom from all-cause mortality between the 3 groups through 5 years were 85.8%, 84.2%, and 88.2%, respectively (p = 0.731). There was no significant difference in all-cause mortality between DCB and PTA through 5 years comparing all patients (unadjusted p = 0.092) or patients with similar characteristics (adjusted p = 0.188).
Conclusions This independent patient-level meta-analysis demonstrates that this paclitaxel DCB is safe. Within DCB patients, there was no correlation between level of paclitaxel exposure and mortality. (Randomized Trial of IN.PACT Admiral® Drug Coated Balloon vs Standard PTA for the Treatment of SFA and Proximal Popliteal Arterial Disease [INPACT SFA I], NCT01175850; IN.PACT Admiral Drug-Coated Balloon vs. Standard Balloon Angioplasty for the Treatment of Superficial Femoral Artery [SFA] and Proximal Popliteal Artery [PPA] [INPACT SFA II], NCT01566461; MDT-2113 Drug-Eluting Balloon vs. Standard PTA for the Treatment of Atherosclerotic Lesions in the Superficial Femoral Artery and/or Proximal Popliteal Artery [MDT-2113 SFA], NCT01947478; The IN.PACT SFA Clinical Study for the Treatment of Atherosclerotic Lesions in the Superficial Femoral Artery and/or Proximal Popliteal Artery Using the IN.PACT Admiral™ Drug-Eluting Balloon in a Chinese Patient Population, NCT02118532; and IN.PACT Global Clinical Study, NCT01609296)
Data was transferred for independent analysis to the Baim Institute for Clinical Research, formerly HCRI. This analysis was funded by Medtronic. Dr. Schneider has served as a member of the advisory board for Medtronic, Abbott, and Boston Scientific; has served as a consultant for Surmodics, Silk Road Medical, Medtronic, Cardinal, CSI, and Profusa; and is a Chief Medical Officer for Intact Vascular and Cagent. Dr. Laird has served on the advisory board for Abbott Vascular and Boston Scientific; has served as a consultant for Abbott Vascular, Philips, Bard/Becton Dickinson, Boston Scientific, and Medtronic; and has received speaking fees from Medtronic. Dr. Doros is a full-time employee of the Baim Institute for Clinical Research; has served as a consultant for Pfizer and Supernus; and has served on the data safety monitoring board for Takeda, Alnylam, and NeoSync. Dr. Gao is a full-time employee of the Baim Institute for Clinical Research. Dr. Ansel has provided advisory and consultation services for Medtronic, CR Bard, Boston Scientific, Cook Medical, Philips Medical, WL Gore, Veryan Medical, Reflow Medical, Shockwave, Intact Vascular, Abbott Vascular, Alucent, Contego Medical, Cardiovascular Systems. Surmodics, Vascular Dynamics, Vatrix, and VIVA Physicians. Dr. Brodmann has received speaking honoraria from Bard Peripheral Vascular, Biotronik, Medtronic, Philips-Spectranetics, Shockwave, Bayer Healthcare, and VIVA Physicians; and is a consultant for Bard Peripheral Vascular, Biotronik, Medtronic, Shockwave, Intact Vascular, Bayer, Sanofi, and Philips-Spectranetics. Dr. Micari has served as a member of the Advisory Board for Medtronic and Boston Scientific; and has served as a consultant for Boston Scientific, Bard, and Terumo. Dr. Shishehbor has served as a consultant and a member of advisory board for Medtronic, Abbott Vascular, Boston Scientific, Philips, and Terumo. Dr. Tepe has received research grants from Medtronic, Bard, Bayer, Gore, Biotronik, and Boston Scientific; and has served as a compensated advisory board member for Medtronic and B Braun. Dr. Zeller has received honoraria from Abbott Vascular, Veryan, Biotronik, Boston Scientific, Cook Medical, Gore and Associates, Medtronic, Philips-Spectranetics, TriReme, and Shockwave; has served as a consultant for Boston Scientific, Cook Medical, Gore and Associates, Medtronic, Spectranetics, Veryan, Intact Vascular, B. Braun, Shockwave, Bayer, and Vesper Medical; has received research, clinical trial, or drug study funds from 480 biomedical, Bard Peripheral Vascular, Veryan, Biotronik, Cook Medical, Gore and Associates, Medtronic, Philips, Terumo, TriReme, Shockwave, Med Alliance, Intact Vascular, and B. Braun; and owns common stock in Veryan and QT Medical.
Listen to this manuscript's audio summary by Editor-in-Chief Dr. Valentin Fuster on JACC.org.
- Received January 7, 2019.
- Revision received January 16, 2019.
- Accepted January 18, 2019.
- 2019 The Authors