Author + information
- Received January 7, 2019
- Revision received January 16, 2019
- Accepted January 18, 2019
- Published online February 6, 2019.
- Peter A. Schneider, MDa,∗ (, )
- John R. Laird, MDb,
- Gheorghe Doros, PhDc,
- Qi Gao, MSd,
- Gary Ansel, MDe,
- Marianne Brodmann, MDf,
- Antonio Micari, MD, PhDg,
- Mehdi H. Shishehbor, DO, MPH, PhDh,
- Gunnar Tepe, MDi and
- Thomas Zeller, MD, PhDj
- aHawaii Permanente Medical Group, Kaiser Foundation Hospital, Honolulu, HI, USA
- bAdventist Heart and Vascular Institute, St. Helena, CA, USA
- cBaim Institute for Clinical Research, Boston, MA, USA
- dBaim Institute for Clinical Research, Boston, MA, USA
- eOhio Health, Riverside Methodist Hospital, Columbus, OH, USA
- 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, OH, USA
- iRoMed Clinic, Rosenheim, Germany
- jUniversitäts-Herzzentrum Freiburg–Bad Krozingen, Bad Krozingen, Germany
- ↵∗Address Correspondence to: Peter A. Schneider, MD Hawaii Permanente Medical Group, Kaiser Foundation Hospital 4644 Aukai Avenue Honolulu, Hawaii 96816 Telephone: 808-282-9953 Twitter: @KPHawaii
Background Five years of prospective clinical trials confirm that paclitaxel drug-coated balloons (DCB) is safe and effective to treat femoropopliteal artery disease. A recent meta-analysis of heterogenous trials of paclitaxel-based balloons and stents reported they are associated with increased mortality and higher doses are linked to higher mortality from 2-5 years.
Objectives: 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 four independently-adjudicated prospective studies of DCB (n=1837) and uncoated percutaneous transluminal angioplasty (PTA; n=143) were included. Extensive analyses of baseline, procedure, and follow-up data of individual patients were performed to explore correlations with long-term mortality. Time to survival by paclitaxel dose tercile was analyzed with adjustment of inverse probability weighting to correct baseline imbalances and study as random effect. Endpoint analyses by treatment were adjusted for study as random effect.
Results There was no statistically significant difference in all-cause mortality between DCB and PTA through 5 years (9.3% vs 11.2%, p=0.399). No deaths were adjudicated by an independent clinical events committee as device-related. A survival analysis stratified nominal paclitaxel dose by low, mid, and upper terciles; mean doses were 5,019.0 μg, 10,007.5 μg, and 19,978.2 μg. There was no statistically significant difference in all-cause mortality between the three groups through 5 years (p=0.700).
Conclusions This independent patient-level meta-analysis demonstrates that paclitaxel DCBs are safe. There is no correlation between any level of paclitaxel exposure and mortality.
Condensed Abstract A recent meta-analysis of heterogenous trials of paclitaxel-based balloons and stents reported they are associated with increased long-term mortality. Data from 4 independently-adjudicated prospective studies of DCBs (n=1837) and PTA (n=143) were included in this patient-level analysis. There was no statistically significant difference in all-cause mortality between DCB and PTA through five years (9.3% vs 11.2%, p=0.399). A survival analysis stratifying paclitaxel dose found no statistically significant difference in all-cause mortality through five years (p=0.700). Paclitaxel DCBs are safe. There is no correlation between any level of paclitaxel exposure and mortality.
Funding: Data was transferred for independent analysis to The Baim Institute for Clinical Research, formerly HCRI (Boston, Massachusetts). This analysis was funded by Medtronic.
Schneider is a member of the advisory board for Medtronic, Abbott, and Boston Scientific and a consultant for Surmodics, Silk Road Medical, Medtronic, Cardinal, CSI, and Profusa. He is a Chief Medical Officer for Intact Vascular and Cagent.
Laird is a member of the advisory board at Abbott Vascular and consults for Abbott Vascular, Bard, Boston Scientific, and Medtronic.
Doros is a full-time employee of the Baim Institute for Clinical Research.
Gao is a full-time employee of the Baim Institute for Clinical Research.
Ansel has provided advisory and consultation services: 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.
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.
Micari is a member of the Advisory Board for Medtronic and Boston Scientific Corp., and a consultant for Boston Scientific Corp, Bard, and Terumo.
Shishehbor is a consultant and a member of advisory board for Medtronic, Abbott Vascular, Boston Scientific, Philips, and Terumo.
Tepe has received research grants from Medtronic, Bard, Gore, Biotronik, Boston Scientific and is a compensated advisory board member for Medtronic, B Braun
Zeller declares honoraria received from Abbott Vascular, Veryan, Biotronik, Boston Scientific Corp., Cook Medical, Gore and Associates, Medtronic, Philips-Spectranetics, TriReme, and Shockwave, consults for Boston Scientific Corp., Cook Medical, Gore and Associates, Medtronic, Spectranetics, Veryan, Intact Vascular, B. Braun, Shockwave, and Bayer; 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; owns common stock in Veryan and QT Medical.
Tweet: Independent patient-level meta-analysis of DCB demonstrates that mortality is not correlated with #paclitaxel exposure
- Received January 7, 2019.
- Revision received January 16, 2019.
- Accepted January 18, 2019.
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