Mortality after Use of Paclitaxel-Coated Balloons Correlates with Total Cumulative Dosage of Paclitaxel in Real-World Analysis
Abstract
:1. Introduction
2. Methods
2.1. Treatment Details and Paclitaxel Dosage
2.2. Statistical Analysis
3. Results
3.1. Demographics, Clinical Characteristics, and Paclitaxel Dosages
3.2. Causes of Death
3.3. Predictors of Mortality after DCB Treatment
3.4. Subgroup Analyses for Predictors of Mortality in the Claudication and CLI Groups
3.5. Analyses for Optimal Cut-off Value of Total Paclitaxel Dosage for Predicting Mortality
4. Discussion
Study Limitations and Significance
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Conflicts of Interest
References
- Rosenfield, K.; Jaff, M.R.; White, C.J.; Rocha-Singh, K.; Mena-Hurtado, C.; Metzger, D.C.; Brodmann, M.; Pilger, E.; Zeller, T.; Krishnan, P.; et al. Trial of a Paclitaxel-Coated Balloon for Femoropopliteal Artery Disease. N. Engl. J. Med. 2015, 373, 145–153. [Google Scholar] [CrossRef] [PubMed]
- Katsanos, K.; Spiliopoulos, S.; Kitrou, P.; Krokidis, M.; Karnabatidis, D. Risk of Death Following Application of Paclitaxel-Coated Balloons and Stents in the Femoropopliteal Artery of the Leg: A Systematic Review and Meta-Analysis of Randomized Controlled Trials. J. Am. Heart Assoc. 2018, 7, e011245. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Food and Drug Administration. Treatment of Peripheral Arterial Disease with Paclitaxel-Coated Balloons and Paclitaxel-Eluting Stents Potentially Associated with Increased Mortality–Letter to Health Care Providers (7 August 2019UPDATE). Available online: www.fda.gov/medical-devices/letters-health-care-providers/update-treatment-peripheral-arterial-disease-paclitaxel-coated-balloons-and-paclitaxel-eluting (accessed on 1 January 2020).
- Nordanstig, J.; James, S.; Andersson, M.; Andersson, M.; Danielsson, P.; Gillgren, P.; Delle, M.; Engstrom, J.; Fransson, T.; Hamoud, M.; et al. Mortality with Paclitaxel-Coated Devices in Peripheral Artery Disease. N. Engl. J. Med. 2020, 383, 2538–2546. [Google Scholar] [CrossRef] [PubMed]
- Schneider, P.A.; Laird, J.R.; Doros, G.; Gao, Q.; Ansel, G.; Brodmann, M.; Micari, A.; Shishehbor, M.H.; Tepe, G.; Zeller, T. Mortality Not Correlated With Paclitaxel Exposure: An Independent Patient-Level Meta-Analysis of a Drug-Coated Balloon. J. Am. Coll. Cardiol. 2019, 73, 2550–2563. [Google Scholar] [CrossRef] [PubMed]
- Secemsky, E.A.; Kundi, H.; Weinberg, I.; Jaff, M.R.; Krawisz, A.; Parikh, S.A.; Beckman, J.A.; Mustapha, J.; Rosenfield, K.; Yeh, R.W. Association of Survival With Femoropopliteal Artery Revascularization With Drug-Coated Devices. JAMA Cardiol. 2019, 4, 332–340. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Behrendt, C.A.; Sedrakyan, A.; Peters, F.; Kreutzburg, T.; Schermerhorn, M.; Bertges, D.J.; Larena-Avellaneda, A.; L’Hoest, H.; Kolbel, T.; Debus, E.S. Editor’s Choice–Long Term Survival after Femoropopliteal Artery Revascularisation with Paclitaxel Coated Devices: A Propensity Score Matched Cohort Analysis. Eur. J. Vasc. Endovasc. Surg. 2020, 59, 587–596. [Google Scholar] [CrossRef] [PubMed]
- Freisinger, E.; Koeppe, J.; Gerss, J.; Goerlich, D.; Malyar, N.M.; Marschall, U.; Faldum, A.; Reinecke, H. Mortality after use of paclitaxel-based devices in peripheral arteries: A real-world safety analysis. Eur. Hearth J. 2020, 41, 3732–3739. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Hill, A.B. The environment and disease: Association or causation? Proc. R. Soc. Med. 1965, 58, 295–300. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Rocha-Singh, K.J.; Duval, S.; Jaff, M.R.; Schneider, P.A.; Ansel, G.M.; Lyden, S.P.; Mullin, C.M.; Ioannidis, J.P.A.; Misra, S.; Tzafriri, A.R.; et al. Mortality and Paclitaxel-Coated Devices: An Individual Patient Data Meta-Analysis. Circulation 2020, 141, 1859–1869. [Google Scholar] [CrossRef] [PubMed]
- AbuRahma, A.F.; AbuRahma, Z.T.; Scott, G.; Adams, E.; Beasley, M.; Davis, M.; Dean, L.S.; Davis, E. Clinical outcome of drug-coated balloon angioplasty in patients with femoropopliteal disease: A real-world single-center experience. J. Vasc. Surg. 2019, 70, 1950–1959. [Google Scholar] [CrossRef] [PubMed]
- Katsanos, K.; Spiliopoulos, S.; Kitrou, P.; Krokidis, M.; Paraskevopoulos, I.; Karnabatidis, D. Risk of Death and Amputation with Use of Paclitaxel-Coated Balloons in the Infrapopliteal Arteries for Treatment of Critical Limb Ischemia: A Systematic Review and Meta-Analysis of Randomized Controlled Trials. J. Vasc. Interv. Radiol. 2020, 31, 202–212. [Google Scholar] [CrossRef] [PubMed]
- Katsanos, K.; Spiliopoulos, S.; Teichgräber, U.; Kitrou, P.; Del Giudice, C.; Björkman, P.; Bisdas, T.; de Boer, S.; Krokidis, M.; Karnabatidis, D. Risk of major amputation following application of paclitaxel coated balloons in the lower limb arteries: A systematic review and meta-analysis of randomised controlled trials. Eur. J. Vasc. Endovasc. Surg. 2021, in press. [Google Scholar] [CrossRef] [PubMed]
- Scheinert, D.; Micari, A.; Brodmann, M.; Tepe, G.; Peeters, P.; Jaff, M.R.; Wang, H.; Schmahl, R.; Zeller, T. IN.PACT Global Study Investigators. Drug-Coated Balloon Treatment for Femoropopliteal Artery Disease. Circ. Cardiovasc. Interv. 2018, 11, e005654. [Google Scholar] [CrossRef] [PubMed]
- Brodmann, M.; Keirse, K.; Scheinert, D.; Spak, L.; Jaff, M.R.; Schmahl, R.; Li, P.; Zeller, T. IN.PACT Global Study Investigators. Drug-Coated Balloon Treatment for Femoropopliteal Artery Disease: The IN.PACT Global Study De Novo In-Stent Restenosis Imaging Cohort. JACC Cardiovasc. Interv. 2017, 10, 2113–2123. [Google Scholar] [CrossRef] [PubMed]
- Thieme, M.; Von Bilderling, P.; Paetzel, C.; Karnabatidis, D.; Perez Delgado, J.; Lichtenberg, M.; Lutonix Global SFA Registry Investigators. The 24-Month Results of the Lutonix Global SFA Registry: Worldwide Experience With Lutonix Drug-Coated Balloon. JACC Cardiovasc. Interv. 2017, 10, 1682–1690. [Google Scholar] [CrossRef] [PubMed]
Patient Characteristics | Survived (n = 169) | Died (n = 56) | p |
---|---|---|---|
Age, years (mean ± SD, range) | 69.57 ± 8.90 (38–88) | 76.27 ± 8.84 (55–93) | <0.001 * |
Male (%) | 140 (82.84) | 42 (75.00) | 0.196 ** |
Hypertension | 139 (82.25) | 48 (85.71) | 0.549 ** |
Diabetes | 117 (69.23) | 43 (76.79) | 0.280 ** |
Coronary artery disease | 74 (43.79) | 22 (39.29) | 0.555 ** |
Smoking | 76 (44.97) | 16 (28.57) | 0.031 ** |
Smoking (current) | 48 (28.40) | 12 (21.43) | 0.306 ** |
Chronic kidney disease | 62 (36.69) | 38 (67.89) | <0.001 ** |
On hemodialysis | 19 (11.24) | 15 (26.79) | 0.005 ** |
Hyperlipidemia | 87 (51.48) | 17 (30.36) | 0.006 ** |
Cerebrovascular attack | 35 (20.71) | 10 (17.86) | 0.644 ** |
Chronic obstructive pulmonary disease | 2 (3.57) | 9 (5.33) | 0.736 † |
Cancer | 30 (17.75) | 17 (30.36) | 0.044 ** |
Cancer newly diagnosed after treatment | 5 (2.96) | 4 (7.14) | |
Active cancer | 13 (7.69) | 7 (12.50) | |
Cured of cancer | 12 (7.10) | 6 (10.71) | |
Previous peripheral revascularization | 20 (11.83) | 12 (21.43) | 0.160 † |
Treatment indication | |||
Claudication | 130 (76.92) | 19 (33.93) | <0.001 ** |
Critical limb ischemia | 39 (23.08) | 37 (66.07) | |
TASC classification | |||
A | 44 (26.04) | 13 (23.21) | 0.967 † |
B | 93 (55.03) | 32 (57.14) | |
C | 24 (14.20) | 8 (14.29) | |
D | 8 (4.73) | 3 (5.36) | |
F/U duration, months | |||
Mean ± SD | 39.81 ± 16.60 | 22.77 ± 17.14 | <0.001 * |
Initial dosage of paclitaxel (mg) | |||
Mean ± SD | 8.65 ± 5.29 | 10.37 ± 6.75 | 0.066 * |
Median (Q1, Q3) | 6.95 (4.75, 10.43) | 8.45 (5.12, 13.60) | |
Min, Max | 1.97, 28.16 | 3.00, 36.41 | |
Total dosage of paclitaxel (mg) | 0.023 * | ||
Mean ± SD | 10.92 ± 7.94 | 14.05 ± 9.88 | |
Median (Q1, Q3) | 8.60 (5.81, 13.61) | 10.43 (6.92, 19.15) | |
Min, Max | 1.97, 52.37 | 3.00, 43.46 | |
Repeated use of DCB | |||
Yes | 37 (21.89) | 16 (28.57) | 0.307 ** |
No | 132 (78.11) | 40 (71.43) | |
Frequency of DCB use | 0.162 * | ||
Mean ± SD | 1.27 ± 0.59 | 1.34 ± 0.61 | |
1 | 135 (79.88) | 41 (73.21) | |
2 | 25 (14.79) | 11 (19.64) | |
3 | 7 (4.14) | 4 (7.14) | |
4 | 2 (1.18) | 0 |
Cause of Death | N (%) |
---|---|
Malignancy | 8 (14.3) |
Lung cancer | 2 (25.0) |
Lymphoma | 2 (25.0) |
Bladder cancer | 1 (12.5) |
Pancreas cancer | 1 (12.5) |
Colon cancer | 1 (12.5) |
Glottic cancer | 1 (12.5) |
Respiratory failure with pneumonia | 7 (12.5) |
Septic shock | 7 (12.5) |
Acute MI or heart failure | 5 (8.9) |
Sudden cardiac arrest | 4 (7.1) |
Senility | 2 (3.6) |
Gastrointestinal bleeding | 1 (1.8) |
Cerebral infarction | 1 (1.8) |
Brain hemorrhage | 1 (1.8) |
Undetermined | 20 (35.7) |
Effect | Hazard Ratio | 95% CI | p-Value | Type 3 Analysis of Effects p-Value | ||
---|---|---|---|---|---|---|
Sex (Female) | 1.525 | 0.832 | 2795 | 0.1721 | 0.1721 | |
Age | 1.086 | 1049 | 1124 | <0.0001 | <0.0001 | |
Critical limb ischemia | 6.040 | 3362 | 10.854 | <0.0001 | <0.0001 | |
Diabetes | 1.581 | 0.847 | 2.951 | 0.1505 | 0.1505 | |
Hypertension | 1.303 | 0.616 | 2.756 | 0.4889 | 0.4889 | |
Hyperlipidemia | 0.446 | 0.252 | 0.790 | 0.0056 | 0.0056 | |
Coronary artery disease | 0.823 | 0.481 | 1.407 | 0.4756 | 0.4756 | |
Smoking | 0.527 | 0.294 | 0.943 | 0.0310 | 0.4756 | |
Smoking (current) | 0.748 | 0.393 | 1.422 | 0.3754 | 0.3754 | |
Chronic kidney disease | 2.881 | 1643 | 5.052 | 0.0002 | 0.0002 | |
Chronic kidney disease on HD | 2.723 | 1498 | 4.949 | 0.0010 | 0.0010 | |
Cerebrovascular attack | 0.831 | 0.419 | 1.647 | 0.5957 | 0.5957 | |
Chronic obstructive pulmonary disease | 0.766 | 0.186 | 3.146 | 0.7112 | 0.7112 | |
Cancer * | 2.159 | 1111 | 4.197 | 0.0233 | 0.0233 | |
Previous peripheral revascularization | 1.638 | 0.863 | 3.109 | 0.1313 | 0.1313 | |
TASC | B vs. A | 1.036 | 0.471 | 2.280 | 1.0000 | 0.9529 |
C vs. A | 0.837 | 0.283 | 2.472 | 1.0000 | ||
D vs. A | 1.131 | 0.243 | 5.258 | 1.0000 | ||
Initial dosage of paclitaxel (mg) | 1.032 | 0.992 | 1.073 | 0.1238 | 0.1238 | |
Total dosage of paclitaxel (mg) ** | 1.040 | 0.996 | 1.086 | 0.0731 | 0.0731 | |
Frequency of DCB use** | 2.021 | 1351 | 3.022 | 0.0006 | 0.0006 |
Effect | Adjusted Hazard Ratio | 95% CI | p-Value | |
---|---|---|---|---|
Age | 1.057 | 1.019 | 1.096 | 0.0032 |
Critical limb ischemia | 4.135 | 2.171 | 7.876 | <0.0001 |
Hyperlipidemia | 0.545 | 0.295 | 1.007 | 0.0526 |
Smoking | 0.993 | 0.523 | 1.886 | 0.9825 |
Chronic kidney disease | 1.784 | 0.933 | 3.410 | 0.0799 |
Chronic kidney disease on HD | 1.340 | 0.635 | 2.830 | 0.4429 |
Cancer * | 1.189 | 0.583 | 2.427 | 0.6336 |
Frequency of DCB use ** | 1.031 | 0.647 | 1.643 | 0.8981 |
Total dosage of paclitaxel (mg) ** | 1.040 | 1.006 | 1.074 | 0.0210 |
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Heo, S.-H.; Woo, S.-Y.; Choi, S.-H.; Park, T.-K.; Do, Y.-S.; Park, K.-B.; Kim, D.-I.; Kim, Y.-W.; Park, Y.-J. Mortality after Use of Paclitaxel-Coated Balloons Correlates with Total Cumulative Dosage of Paclitaxel in Real-World Analysis. J. Clin. Med. 2021, 10, 3747. https://doi.org/10.3390/jcm10163747
Heo S-H, Woo S-Y, Choi S-H, Park T-K, Do Y-S, Park K-B, Kim D-I, Kim Y-W, Park Y-J. Mortality after Use of Paclitaxel-Coated Balloons Correlates with Total Cumulative Dosage of Paclitaxel in Real-World Analysis. Journal of Clinical Medicine. 2021; 10(16):3747. https://doi.org/10.3390/jcm10163747
Chicago/Turabian StyleHeo, Seon-Hee, Shin-Young Woo, Seung-Hyuk Choi, Taek-Kyu Park, Young-Soo Do, Kwang-Bo Park, Dong-Ik Kim, Young-Wook Kim, and Yang-Jin Park. 2021. "Mortality after Use of Paclitaxel-Coated Balloons Correlates with Total Cumulative Dosage of Paclitaxel in Real-World Analysis" Journal of Clinical Medicine 10, no. 16: 3747. https://doi.org/10.3390/jcm10163747