Five-Year Comparative Efficacy of Everolimus-Eluting vs. Resolute Zotarolimus-Eluting Stents in Patients with Acute Coronary Syndrome Undergoing Percutaneous Coronary Intervention
Abstract
1. Introduction
2. Methods
2.1. Study End Points
2.2. Statistical Analysis
3. Results
3.1. Primary Endpoint
3.2. Secondary Endpoints
All-Cause Mortality
3.3. Myocardial Infarction
3.4. Repeat PCI and Stroke
3.5. DES Performance in Pre-Specified Subgroups
4. Discussion
5. Limitations
6. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
Abbreviations
ACS | acute coronary syndrome |
ACTION-ACS | international acute coronary syndrome registry |
BMS | bare metal stents |
CAD | coronary artery disease |
CCS | Canadian Cardiovascular Society Grading Angina |
DES | drug-eluting stents |
EES | everolimus-eluting stents |
MACCE | major adverse cardiovascular and cerebrovascular events |
MI | myocardial infarction |
NSTEMI | Non-ST-Segment Elevation Myocardial Infarction |
NYHA | New York Heart Association heart failure classification |
PCI | percutaneous coronary intervention |
R-ZES | Resolute zotarolimus-eluting stents |
STEMI-ST | Segment Elevation Myocardial Infarction |
UA | unstable angina |
References
- Navarese, E.P.; Kowalewski, M.; Kandzari, D.; Lansky, A.; Górny, B.; Kołtowski, Ł.; Waksman, R.; Berti, S.; Musumeci, G.; Limbruno, U.; et al. First-generation versus second-generation drug-eluting stents in current clinical practice: Updated evidence from a comprehensive meta-analysis of randomised clinical trials comprising 31 379 patients. Open Heart 2014, 1, e000064. [Google Scholar] [CrossRef] [PubMed]
- Fox, K.A.; Carruthers, K.F.; Dunbar, D.R.; Graham, C.; Manning, J.R.; De Raedt, H.; Buysschaert, I.; Lambrechts, D.; Van De Werf, F. Underestimated and under-recognized: The late consequences of acute coronary syndrome (GRACE UK-Belgian Study). Eur. Heart J. 2010, 31, 2755–2764. [Google Scholar] [CrossRef] [PubMed]
- Rossello, X.; Bueno, H.; Pocock, S.J.; Van De Werf, F.; Danchin, N.; Annemans, L.; Medina, J.; Zeymer, U. Predictors of all-cause mortality and ischemic events within and beyond 1 year after an acute coronary syndrome: Results from the EPICOR registry. Clin. Cardiol. 2019, 42, 111–119. [Google Scholar] [CrossRef] [PubMed]
- Zocca, P.; Kok, M.M.; Tandjung, K.; Danse, P.W.; Jessurun, G.A.J.; Hautvast, R.W.M.; van Houwelingen, K.G.; Stoel, M.G.; Schramm, A.R.; Gin, R.M.T.J.; et al. 5-Year Outcome Following Random-ized Treatment of All-Comers With Zotarolimus-Eluting Resolute Integrity and Everolimus-Eluting PROMUS Element Coronary Stents: Final Report of the DUTCH PEERS (TWENTE II) Trial. JACC Cardiovasc. Interv. 2018, 11, 462–469. [Google Scholar] [CrossRef] [PubMed]
- von Birgelen, C.; van der Heijden, L.C.; Basalus, M.W.; Kok, M.M.; Sen, H.; Louwerenburg, H.W.; van Houwelingen, K.G.; Stoel, G.M.; de Man, F.H.A.F.; Linssen, G.C.; et al. Five-Year Outcome After Implantation of Zotarolimus- and Everolimus-Eluting Stents in Randomized Trial Participants and Nonenrolled Eligible Patients: A Secondary Analysis of a Randomized Clinical Trial. JAMA Cardiol. 2017, 2, 268–276. [Google Scholar] [CrossRef]
- Garcia-Garcia, H.M.; McFadden, E.P.; Fearon, W.F.; Taggart, D.; Kappetein, A.-P.; Krucoff, M.W.; Vranckx, P.; Windecker, S.; Cutlip, D.; Serruys, P.W.; et al. Standardized End Point Definitions for Coronary Intervention Trials: The Academic Research Consortium-2 Consensus Document. Circulation 2018, 137, 2635–2650. [Google Scholar] [CrossRef]
- Thygesen, K.; Alpert, J.S.; Jaffe, A.S.; Chaitman, B.R.; Bax, J.J.; Morrow, D.A.; White, H.D.; ESC Scientific Document Group. Fourth Universal Definition of Myocardial Infarction (2018). Circulation 2018, 138, e618–e651. [Google Scholar] [CrossRef]
- Austin, P.C. An Introduction to Propensity Score Methods for Reducing the Effects of Confounding in Observational Studies. Multivar. Behav. Res. 2011, 46, 399–424. [Google Scholar] [CrossRef]
- Heinze, G.; Wallisch, C.; Dunkler, D. Variable selection-A review and recommendations for the practicing statistician. Biom. J. 2018, 60, 431–449. [Google Scholar] [CrossRef]
- Stuart, E.A. Matching Methods for Causal Inference: A Review and a Look Forward. Stat. Sci. 2010, 25, 1–21. [Google Scholar] [CrossRef]
- Navarese, E.P.; Kowalewski, M.; Kubica, J.; Kelm, M.; De Boer, M.-J.; Waksman, R.; Suryapranata, H.; Cortese, B.; Kandzari, D.; Dias, S.; et al. Short and long-term safety and efficacy of polymer-free vs. durable polymer drug-eluting stents. A comprehensive meta-analysis of randomized trials including 6178 patients. Atherosclerosis 2014, 233, 224–231. [Google Scholar] [CrossRef] [PubMed]
- Navarese, E.P.; Dj, K.; Claessen, B.; Andreotti, F.; Kowalewski, M.; Kandzari, D.E.; Kereiakes, D.J.; Waksman, R.; Mauri, L.; Meredith, I.T.; et al. Safety and efficacy outcomes of first and second generation durable polymer drug eluting stents and biodegradable polymer biolimus eluting stents in clinical practice: Comprehensive network meta-analysis. BMJ 2013, 347, f6530. [Google Scholar] [CrossRef] [PubMed]
- Kolandaivelu, K.; Swaminathan, R.; Gibson, W.J.; Kolachalama, V.B.; Nguyen-Ehrenreich, K.-L.; Giddings, V.L.; Coleman, L.; Wong, G.K.; Edelman, E.R. Stent Thrombogenicity Early in High-Risk Interventional Settings Is Driven by Stent Design and Deployment and Protected by Polymer-Drug Coatings. Circulation 2011, 123, 1400–1409. [Google Scholar] [CrossRef] [PubMed]
- Polimeni, A.; Sorrentino, S.; Spaccarotella, C.; Mongiardo, A.; Sabatino, J.; De Rosa, S.; Gori, T.; Indolfi, C. Stent Thrombosis After Percu-taneous Coronary Intervention: From Bare-Metal to the Last Generation of Drug-Eluting Stents. Cardiol. Clin. 2020, 38, 639–647. [Google Scholar] [CrossRef]
- Navarese, E.P.; Kowalewski, M.; Andreotti, F.; van Wely, M.; Camaro, C.; Kolodziejczak, M.; Gorny, B.; Wirianta, J.; Kubica, J.; Kelm, M.; et al. Meta-analysis of time-related benefits of statin therapy in patients with acute coronary syndrome undergoing percutaneous coronary intervention. Am. J. Cardiol. 2014, 113, 1753–1764. [Google Scholar] [CrossRef]
- Navarese, E.P.; Andreotti, F.; Schulze, V.; Kołodziejczak, M.; Buffon, A.; Brouwer, M.; Costa, F.; Kowalewski, M.; Parati, G.; Lip, G.Y.H.; et al. Optimal duration of dual an-tiplatelet therapy after percutaneous coronary intervention with drug eluting stents: Meta-analysis of randomised con-trolled trials. BMJ 2015, 350, h1618. [Google Scholar] [CrossRef]
- Turpie, A.G.G. Burden of disease: Medical and economic impact of acute coronary syndromes. Am. J. Manag. Care 2006, 12 (Suppl. 16), S430–S434. [Google Scholar]
- Joner, M.; Finn, A.V.; Farb, A.; Mont, E.K.; Kolodgie, F.D.; Ladich, E.; Kutys, R.; Skorija, K.; Gold, H.K.; Virmani, R. Pathology of Drug-Eluting Stents in Humans: De-layed Healing and Late Thrombotic Risk. J. Am. Coll. Cardiol. 2006, 48, 193–202. [Google Scholar] [CrossRef]
- Renu, V.; Giulio, G.; Andrew, F.; Giuseppe, M.; Niccolo, G.; Teresio, M.; Mihalcsik, L.; Tespili, M.; Valsecchi, O.; Kolodgie, F.D. Localized Hypersensitivity and Late Coronary Thrombosis Secondary to a Sirolimus-Eluting Stent. Circulation 2004, 109, 701–705. [Google Scholar]
- Wilson, G.J.; Nakazawa, G.; Schwartz, R.S.; Huibregtse, B.; Poff, B.; Herbst, T.J.; Baim, D.S.; Virman, R. Comparison of Inflammatory Response After Implantation of Sirolimus- and Paclitaxel-Eluting Stents in Porcine Coronary Arteries. Circulation 2009, 120, 141–149. [Google Scholar] [CrossRef]
- Taniwaki, M.; Radu, M.D.; Zaugg, S.; Amabile, N.; Garcia-Garcia, H.M.; Yamaji, K.; Jørgensen, E.; Kelbæk, H.; Pilgrim, T.; Caussin, C.; et al. Mechanisms of Very Late Drug-Eluting Stent Thrombosis Assessed by Optical Coherence Tomography. Circulation 2016, 133, 650–660. [Google Scholar] [CrossRef] [PubMed]
- Guagliumi, G.; Sirbu, V.; Musumeci, G.; Gerber, R.; Biondi-Zoccai, G.; Ikejima, H.; Ladich, E.; Lortkipanidze, N.; Matiashvili, A.; Valsecchi, O.; et al. Examination of the In Vivo Mecha-nisms of Late Drug-Eluting Stent Thrombosis: Findings From Optical Coherence Tomography and Intravascular Ultra-sound Imaging. JACC Cardiovasc. Interv. 2012, 5, 12–20. [Google Scholar] [CrossRef] [PubMed]
- Otsuka, F.; Nakazawa, G.; Nakano, M.; Vorpahl, M.; Yazdani, S.K.; Ladich, E.; Kolodgie, F.D.; Finn, A.V.; Virmani, R. The pathology of neoatherosclerosis in human coronary bare metal and drug-eluting stent implants. J. Am. Coll. Cardiol. 2011, 57, E2051. [Google Scholar] [CrossRef]
- Nakazawa, G.; Finn, A.V.; Joner, M.; Ladich, E.; Kutys, R.; Mont, E.K.; Gold, H.K.; Burke, P.A.; Kolodgie, F.D.; Virmani, R. Delayed arterial healing and increased late stent thrombosis at culprit sites after drug-eluting stent placement for acute myocardial infarction patients: An autopsy study. Circulation 2008, 118, 1138–1145. [Google Scholar] [CrossRef]
- Lagerqvist, B.; James, S.K.; Stenestrand, U.; Lindbäck, J.; Nilsson, T.; Wallentin, L. Long-Term Outcomes with Drug-Eluting Stents versus Bare-Metal Stents in Sweden. N. Engl. J. Med. 2007, 356, 1009–1019. [Google Scholar] [CrossRef] [PubMed]
- Wańha, W.; Mielczarek, M.; Roleder, T.; Ładziński, S.; Milewski, M.; Gilis-Malinowska, N.; Chmielecki, M.; Ciećwierz, D.; Bachorski, W.; Kunik, P.; et al. New-generation drug eluting stent vs. bare metal stent in saphenous vein graft-1 year outcomes by a propensity score ascertainment (SVG Baltic Registry). Int. J. Cardiol. 2019, 292, 56–61. [Google Scholar] [CrossRef] [PubMed]
- Habib, A.; Karmali, V.; Polavarapu, R.; Akahori, H.; Cheng, Q.; Pachura, K.; Kolodgie, F.D.; Finn, A.V. Sirolimus-FKBP12.6 impairs endothelial bar-rier function through protein kinase C-α activation and disruption of the p120-vascular endothelial cadherin interaction. Arterioscler. Thromb. Vasc. Biol. 2013, 33, 2425–2431. [Google Scholar] [CrossRef]
- Navarese, E.P.; Khan, S.U.; Kołodziejczak, M.; Kubica, J.; Buccheri, S.; Cannon, C.P.; Gurbel, P.A.; de Servi, S.; Budaj, A.; Bartorelli, A.; et al. Comparative Efficacy and Safety of Oral P2Y(12) Inhibitors in Acute Coronary Syndrome: Network Meta-Analysis of 52 816 Patients From 12 Randomized Trials. Circulation 2020, 142, 150–160. [Google Scholar] [CrossRef]
- Fox, K.A.A.; Metra, M.; Morais, J.; Atar, D. The myth of ’stable’ coronary artery disease. Nat. Rev. Cardiol. 2020, 17, 9–21. [Google Scholar] [CrossRef]
- Attizzani, G.F.; Capodanno, D.; Ohno, Y.; Tamburino, C. Mechanisms, pathophysiology, and clinical aspects of incom-plete stent apposition. J. Am. Coll. Cardiol. 2014, 63, 1355–1367. [Google Scholar] [CrossRef]
- Gogas, B.D.; McDaniel, M.; Samady, H.; King, S.B. Novel drug-eluting stents for coronary revascularization. Trends Cardiovasc. Med. 2014, 24, 305–313. [Google Scholar] [CrossRef]
- Rizas, K.D.; Mehilli, J. Stent Polymers: Do They Make a Difference? Circ. Cardiovasc. Interv. 2016, 9, e002943. [Google Scholar] [CrossRef] [PubMed]
- Torii, S.; Jinnouchi, H.; Sakamoto, A.; Kutyna, M.; Cornelissen, A.; Kuntz, S.; Guo, L.; Mori, H.; Harari, E.; Paek, K.H.; et al. Drug-eluting coronary stents: Insights from preclinical and pathology studies. Nat. Rev. Cardiol. 2020, 17, 37–51. [Google Scholar] [CrossRef] [PubMed]
- Mori, H.; Otsuka, F.; Gupta, A.; Jinnouchi, H.; Torii, S.; Harari, E.; Virmani, R.; Finn, A.V. Revisiting the role of durable polymers in cardiovas-cular devices. Expert Rev. Cardiovasc. Ther. 2017, 15, 835–846. [Google Scholar] [CrossRef]
- Szott, L.M.; Irvin, C.A.; Trollsås, M.; Hossainy, S.; Ratner, B.D. Blood compatibility assessment of polymers used in drug eluting stent coatings. Biointerphases 2016, 11, 029806. [Google Scholar] [CrossRef]
- Torii, S.; Cheng, Q.; Finn, A.V.; Mori, H.; Lipinski, M.J.; Acampado, E.; Perkins, L.E.; Hossainy, S.F.; Pacetti, S.D.; Kolodgie, F.D.; et al. Acute thrombogenicity of fluoropolymer-coated versus biodegradable and polymer-free stents. EuroIntervention 2019, 14, 1685–1693. [Google Scholar] [CrossRef] [PubMed]
- Giustino, G.; Harari, R.; Baber, U.; Sartori, S.; Stone, G.W.; Leon, M.B.; Windecker, S.; Serruys, P.W.; Kastrati, A.; von Birgelen, C.; et al. Long-term Safety and Efficacy of New-Generation Drug-Eluting Stents in Women With Acute Myocardial Infarction: From the Women in Innovation and Drug-Eluting Stents (WIN-DES) Collaboration. JAMA Cardiol. 2017, 2, 855–862. [Google Scholar] [CrossRef] [PubMed]
- Kirtane, A.J.; Yeung, A.C.; Ball, M.; Carr, J.; O’Shaughnessy, C.; Mauri, L.; Liu, M.; Leon, M.B. Long-term (5-year) clinical evaluation of the Resolute zotarolimus-eluting coronary stent: The RESOLUTE US clinical trial. Catheter. Cardiovasc. Interv. 2020, 95, 1067–1073. [Google Scholar] [CrossRef]
- Wiemer, M.; Serruys, P.W.; Miquel-Hebert, K.; Neumann, F.J.; Piek, J.J.; Grube, E.; Haase, J.; Thuesen, L.; Hamm, C. Five-year long-term clinical follow-up of the XIENCE V everolimus eluting coronary stent system in the treatment of patients with de novo coronary artery le-sions: The SPIRIT FIRST trial. Catheter. Cardiovasc. Interv. Off. J. Soc. Card. Angiogr. Interv. 2010, 75, 997–1003. [Google Scholar]
- Mehilli, J.; Richardt, G.; Valgimigli, M.; Schulz, S.; Singh, A.; Abdel-Wahab, M.; Tiroch, K.; Pache, J.; Hausleiter, J.; Byrne, R.A.; et al. Zotarolimus- Versus Everolimus-Eluting Stents for Unprotected Left Main Coronary Artery Disease. J. Am. Coll. Cardiol. 2013, 62, 2075–2082. [Google Scholar] [CrossRef]
- Serruys, P.; Silber, S.; Garg, S.; van Geuns, R.J.; Richard, G.; Buszman, P.; Kelbaek, H.; van Boven, A.J.; Hofma, S.; Linke, A.; et al. Comparison of Zotarolimus-Eluting and Everolimus-Eluting Coronary Stents. N. Engl. J. Med. 2010, 363, 136–146. [Google Scholar] [CrossRef] [PubMed]
- Von Birgelen, C.; Basalus, M.W.Z.; Tandjung, K.; van Houwelingen, K.G.; Stoel, M.G.; Louwerenburg, J.H.W.; Linssen, G.C.M.; Saïd, S.A.M.; Kleijne, M.A.W.J.; Sen, H.; et al. A randomized controlled trial in second-generation zotarolimus-eluting Resolute stents versus everolimus-eluting Xience V stents in real-world patients: The TWENTE trial. J. Am. Coll. Cardiol. 2012, 59, 1350–1361. [Google Scholar] [CrossRef]
- Kang, D.-Y.; Lee, C.H.; Lee, P.H.; Ahn, J.-M.; Lee, S.-W.; Kim, Y.-H.; Park, S.; Nam, C.W.; Choi, Y.S.; Rha, S.; et al. Comparison of Resolute zotarolimus-eluting and Xience everolimus-eluting stents in patients with de novo long coronary artery lesions: A randomized LONG-DES VI trial. Coron. Artery Dis. 2019, 30, 59–66. [Google Scholar] [CrossRef] [PubMed]
- Iqbal, J.; Serruys, P.W.; Silber, S.; Kelbaek, H.; Richardt, G.; Morel, M.-A.; Negoita, M.; Buszman, P.E.; Windecker, S. Comparison of zotarolimus- and everolimus-eluting coronary stents: Final 5-year report of the RESOLUTE all-comers trial. Circ. Cardiovasc. Interv. 2015, 8, e002230. [Google Scholar] [CrossRef]
- Mori, H.; Atmakuri, D.R.; Torii, S.; Braumann, R.; Smith, S.; Jinnouchi, H.; Gupta, A.; Harari, E.; Shkullaku, M.; Kutys, R.; et al. Very Late Pathological Responses to Cobalt–Chromium Everolimus-Eluting, Stainless Steel Sirolimus-Eluting, and Cobalt–Chromium Bare Metal Stents in Humans. J. Am. Hear. Assoc. 2017, 6. [Google Scholar] [CrossRef] [PubMed]
- Sabate, M.; Cequier, A.; Iñiguez, A.; Serra, A.; Hernandez-Antolin, R.; Mainar, V.; Valgimigli, M.; Tespili, M.; Heijer, P.D.; Bethencourt, A.; et al. Everolimus-eluting stent versus bare-metal stent in ST-segment elevation myocardial infarction (EXAMINATION): 1 year results of a randomised controlled trial. Lancet 2012, 380, 1482–1490. [Google Scholar] [CrossRef]
Patient Characteristics | EES | R-ZES | p Value |
---|---|---|---|
(n = 2483) | (n = 1014) | ||
Women, n (%) | 803 (32.3) | 340 (33.5) | 0.7 |
Age, mean ± SD | 65.16 (10.3) | 64.99 (10.2) | 0.4 |
Diabetes, n (%) | 861 (34.7) | 362 (35.7) | 0.5 |
CCSIII.IV, n (%) | 1818 (73.2) | 765 (75.4) | 0.1 |
Hypertension, n (%) | 2131 (85.8) | 881 (86.9) | 0.4 |
BMI, n (%) | 28.44 (4.4) | 28.16 (4.1) | 0.2 |
Dyslipidemia, n (%) | 1575 (63.4) | 671 (66.2) | 0.1 |
Anemia, n (%) | 388 (15.6) | 153 (15.1) | 0.6 |
NYHA, n (%) | 0.3 | ||
NYHA class II | 295 (11.9) | 100 (9.9) | |
NYHA class III | 174 (7) | 64 (6.3) | |
NYHA class IV | 51 (2.1) | 20 (2.0) | |
Radial access, n (%) | 2185 (88.0) | 919 (90.6) | 0.3 |
MVD, n (%) | 474 (19.1) | 192 (18.9) | 0.9 |
Bifurcation, n (%) | 92 (3.7) | 40 (3.9) | 0.7 |
Adjunctive therapies | |||
IABP, n (%) | 25 (1.0) | 9 (0.9) | 0.7 |
Thrombectomy, n (%) | 52 (2.0) | 19 (1.8) | 0.2 |
GP IIB/IIIa inh, n(%) | 151 (6.1) | 52 (5.1) | 0.4 |
Culprit vessel PCI | |||
PCI Cx, n (%) | 596 (24.0) | 224 (22.1) | 0.2 |
PCI LAD, n (%) | 1135 (45.7) | 469 (46.3) | 0.7 |
PCI RCA, n (%) | 654 (26.3) | 258 (25.4) | 0.5 |
PCI LM, n (%) | 107 (4.3) | 34 (3.4) | 0.1 |
Residual stenosis, n (%) | 13 (0.5) | 4 (0.4) | 0.4 |
Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations. |
© 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
Share and Cite
Koni, E.; Wanha, W.; Ratajczak, J.; Zhang, Z.; Podhajski, P.; Musci, R.L.; Sangiorgi, G.M.; Kaźmierski, M.; Buffon, A.; Kubica, J.; et al. Five-Year Comparative Efficacy of Everolimus-Eluting vs. Resolute Zotarolimus-Eluting Stents in Patients with Acute Coronary Syndrome Undergoing Percutaneous Coronary Intervention. J. Clin. Med. 2021, 10, 1278. https://doi.org/10.3390/jcm10061278
Koni E, Wanha W, Ratajczak J, Zhang Z, Podhajski P, Musci RL, Sangiorgi GM, Kaźmierski M, Buffon A, Kubica J, et al. Five-Year Comparative Efficacy of Everolimus-Eluting vs. Resolute Zotarolimus-Eluting Stents in Patients with Acute Coronary Syndrome Undergoing Percutaneous Coronary Intervention. Journal of Clinical Medicine. 2021; 10(6):1278. https://doi.org/10.3390/jcm10061278
Chicago/Turabian StyleKoni, Endrin, Wojciech Wanha, Jakub Ratajczak, Zhongheng Zhang, Przemysław Podhajski, Rita L. Musci, Giuseppe M. Sangiorgi, Maciej Kaźmierski, Antonio Buffon, Jacek Kubica, and et al. 2021. "Five-Year Comparative Efficacy of Everolimus-Eluting vs. Resolute Zotarolimus-Eluting Stents in Patients with Acute Coronary Syndrome Undergoing Percutaneous Coronary Intervention" Journal of Clinical Medicine 10, no. 6: 1278. https://doi.org/10.3390/jcm10061278
APA StyleKoni, E., Wanha, W., Ratajczak, J., Zhang, Z., Podhajski, P., Musci, R. L., Sangiorgi, G. M., Kaźmierski, M., Buffon, A., Kubica, J., Wojakowski, W., & Navarese, E. P. (2021). Five-Year Comparative Efficacy of Everolimus-Eluting vs. Resolute Zotarolimus-Eluting Stents in Patients with Acute Coronary Syndrome Undergoing Percutaneous Coronary Intervention. Journal of Clinical Medicine, 10(6), 1278. https://doi.org/10.3390/jcm10061278