Catheterization and Cardiovascular Interventions 84:1061 (2014)
Editorial Comment Drug-Eluting Stents: Newer is Better! Augusto C. Lopes,1,2 MD and Pedro A. Lemos3* MD, PhD 1 Edelman Laboratory, Institute of Medical Engineering and Science, Massachusetts Institute of Technology, Cambridge, Massachusetts 2 Cardiovascular Division, Brigham and Women’s Hospital, Harvard Medical School, Boston, Massachusetts 3 Department of Interventional Cardiology, Heart ~o Paulo Medical Institute (InCor), University of Sa School, Sao Paulo, Brazil
More than one decade ago, the introduction of early drug-eluting stents (DES) reduced clinical restenosis to a single-digit risk in most subsets. Subsequently, however, issues related to late safety were raised, as experience with DES increased. With an ultimate aim of improving clinical outcomes, newer-generation DES have been progressively developed over the last years. Stents are complex biodevices and their final performance is most likely driven by a synergistic effect of the whole construct, instead of being resultant of any component in particular. For newer-generation DES, virtually all stent elements were re-engineered to incorporate combined enhancements in the bioactive agent (e.g., limus-drug, lower dosages, improved kinetics), the platform (e.g., thinner struts), the coating (e.g., thinner, more biocompatible, abluminal), and the delivery system (e.g., lower profile, less balloon overhanging). A number of clinical trials have compared newer DES to previous formulations. Differently from the “bare metal stent versus drug-eluting stent” era, however, the current “drug-eluting stent versus drug-eluting stent” time requires much larger patient datasets and much longer observation periods to properly explore the treatment effects, due to the low frequency and late occurrence of many variables of interest, such as stent thrombosis [1]. In this issue of CCI, Omar et al. present a large single center registry composed of 1,612 patients with acute coronary syndrome and a predominance of complex (type C) lesions, a population known to be at higher risk of thrombotic events. The long-term safety and efficacy of second generation everolimus-eluting C 2014 Wiley Periodicals, Inc. V
stent (EES) was compared to other second-generation DES (zotarolimus-eluting stent), first-generation sirolimus-eluting stent, and bare metal stent. The primary endpoint was defined as the composite of all-cause death, Q-wave myocardial infarction and target lesion revascularization after 3 years. In spite of the high-risk profile, patients treated with EES had remarkable outcomes, with the lowest rate of clinical restenosis and a risk of thrombosis that was as low as that observed after bare stent implantation, even after multivariate adjustment. It is clear that the work by Omar et al. has several limitations related to its observational nature. Nevertheless, their study gives a clear-cut vision of the clinical performance of newer-generation DES in the daily practice, which had an overall better performance than any other tested stent, providing the lowest risk of repeat revascularization while minimizing the risk of thrombosis. Current DES establish a tough benchmark to be overcome by future devices and techniques. Unless suitable surrogate markers are developed and validated [2], proof of clinical superiority (or noninferiority) for any new technology in coronary interventional cardiology will become a scientific challenge, requiring a combination of intelligent study designing and large study populations followed for long periods of time. REFERENCES 1. Palmerini T, Biondi-Zoccai G, Della Riva D, Mariani A, Sabate M, Smits PC, Kaiser C, D’Ascenzo F, Frati G, Mancone M, Genereux P, Stone GW. Clinical outcomes with bioabsorbable polymer- versus durable polymer-based drug-eluting and baremetal stents: Evidence from a comprehensive network meta-analysis. J Am Coll Cardiol 2014;63:299–307. 2. Campos CM, Lemos PA. Bioresorbable vascular scaffolds: novel devices, novel interpretations, and novel interventions strategies. Catheter Cardiovasc Interv 2014;84:46–47. Conflict of interest: Nothing to report. *Correspondence to: Pedro A. Lemos, MD, PhD; Av. Dr. Eneas de Carvalho Aguiar, 44, Bloco I, 3o andar, Hemodin^amica, S~ao PauloSP 05403-000, Brazil. E-mail: [email protected] Received 7 October 2014; Revision accepted 10 October 2014 DOI: 10.1002/ccd.25702 Published online 19 November 2014 in Wiley Online Library (wileyonlinelibrary.com)
Editorial Comment Drug-Eluting Stents: Newer is Better! Augusto C. Lopes,1,2 MD and Pedro A. Lemos3* MD, PhD 1 Edelman Laboratory, Institute of Medical Engineering and Science, Massachusetts Institute of Technology, Cambridge, Massachusetts 2 Cardiovascular Division, Brigham and Women’s Hospital, Harvard Medical School, Boston, Massachusetts 3 Department of Interventional Cardiology, Heart ~o Paulo Medical Institute (InCor), University of Sa School, Sao Paulo, Brazil
More than one decade ago, the introduction of early drug-eluting stents (DES) reduced clinical restenosis to a single-digit risk in most subsets. Subsequently, however, issues related to late safety were raised, as experience with DES increased. With an ultimate aim of improving clinical outcomes, newer-generation DES have been progressively developed over the last years. Stents are complex biodevices and their final performance is most likely driven by a synergistic effect of the whole construct, instead of being resultant of any component in particular. For newer-generation DES, virtually all stent elements were re-engineered to incorporate combined enhancements in the bioactive agent (e.g., limus-drug, lower dosages, improved kinetics), the platform (e.g., thinner struts), the coating (e.g., thinner, more biocompatible, abluminal), and the delivery system (e.g., lower profile, less balloon overhanging). A number of clinical trials have compared newer DES to previous formulations. Differently from the “bare metal stent versus drug-eluting stent” era, however, the current “drug-eluting stent versus drug-eluting stent” time requires much larger patient datasets and much longer observation periods to properly explore the treatment effects, due to the low frequency and late occurrence of many variables of interest, such as stent thrombosis [1]. In this issue of CCI, Omar et al. present a large single center registry composed of 1,612 patients with acute coronary syndrome and a predominance of complex (type C) lesions, a population known to be at higher risk of thrombotic events. The long-term safety and efficacy of second generation everolimus-eluting C 2014 Wiley Periodicals, Inc. V
stent (EES) was compared to other second-generation DES (zotarolimus-eluting stent), first-generation sirolimus-eluting stent, and bare metal stent. The primary endpoint was defined as the composite of all-cause death, Q-wave myocardial infarction and target lesion revascularization after 3 years. In spite of the high-risk profile, patients treated with EES had remarkable outcomes, with the lowest rate of clinical restenosis and a risk of thrombosis that was as low as that observed after bare stent implantation, even after multivariate adjustment. It is clear that the work by Omar et al. has several limitations related to its observational nature. Nevertheless, their study gives a clear-cut vision of the clinical performance of newer-generation DES in the daily practice, which had an overall better performance than any other tested stent, providing the lowest risk of repeat revascularization while minimizing the risk of thrombosis. Current DES establish a tough benchmark to be overcome by future devices and techniques. Unless suitable surrogate markers are developed and validated [2], proof of clinical superiority (or noninferiority) for any new technology in coronary interventional cardiology will become a scientific challenge, requiring a combination of intelligent study designing and large study populations followed for long periods of time. REFERENCES 1. Palmerini T, Biondi-Zoccai G, Della Riva D, Mariani A, Sabate M, Smits PC, Kaiser C, D’Ascenzo F, Frati G, Mancone M, Genereux P, Stone GW. Clinical outcomes with bioabsorbable polymer- versus durable polymer-based drug-eluting and baremetal stents: Evidence from a comprehensive network meta-analysis. J Am Coll Cardiol 2014;63:299–307. 2. Campos CM, Lemos PA. Bioresorbable vascular scaffolds: novel devices, novel interpretations, and novel interventions strategies. Catheter Cardiovasc Interv 2014;84:46–47. Conflict of interest: Nothing to report. *Correspondence to: Pedro A. Lemos, MD, PhD; Av. Dr. Eneas de Carvalho Aguiar, 44, Bloco I, 3o andar, Hemodin^amica, S~ao PauloSP 05403-000, Brazil. E-mail: [email protected] Received 7 October 2014; Revision accepted 10 October 2014 DOI: 10.1002/ccd.25702 Published online 19 November 2014 in Wiley Online Library (wileyonlinelibrary.com)
