Author + information
- Michael A. Kutcher, MD∗ ()
- ↵∗Address for correspondence:
Dr. Michael A. Kutcher, Section of Cardiovascular Medicine, Wake Forest School of Medicine, 1 Medical Center Boulevard, Winston-Salem, North Carolina 27157.
With the disappointing long-term results of the first generation of fully bioresorbable scaffolds, there is increased interest in the long-term results of hybrid metal-based coronary stents that have a biodegradable polymer platform for the elution of antiproliferative agents. In this issue of JACC: Cardiovascular Interventions, the study by Lefèvre et al. (1) on the 5-year follow-up to the BIOFLOW-II (BIOTRONIK-Safety and Clinical PerFormance of the Drug-ELuting Orsiro Stent in the Treatment of Subjects With Single de Novo Coronary Artery Lesions) trial provides important data considering long-term outcomes.
Before going into the details of the BIOFLOW-II trial and its juxtaposition with other long-term trials, the following points should be made. The technology of novel intracoronary stents has impressively evolved into 4 major classes: bare-metal stents, durable-polymer drug-eluting stents (DP-DES), biodegradable-polymer drug-eluting stents (BP-DES), and fully bioresorbable scaffolds. The important technological attributes of the BP-DES class are the metallic stent elements, the thickness of the stent struts, the biodegradable polymer, the polymer location (abluminal [only on the intimal or media side of the stent] or circumferential [all around the stent]), the degradation time of the polymer, the antiproliferative agent (drug), and the drug-elution kinetics.
The Orsiro stent (BIOTRONIK, Bulach, Switzerland) is a cobalt-chromium stent with 60- or 80-μm strut thickness (for stent diameters 2.25 to 3.00 mm and 3.50 to 4.00 mm, respectively). It has a passive silicon carbide stent coating and an active biodegradable poly-L-lactic polymer in a circumferential pattern. The poly-L-lactic polymer is degraded over 12 to 24 months. The antiproliferative agent is sirolimus, which is fully eluted at 3 months (2). The BIOFLOW-II trial was a multicenter, assessor-blinded, European trial that randomized 452 patients with 505 lesions to either the Orsiro stent or a DP-DES (XIENCE PRIME everolimus-eluting stent [X-EES], Abbott Vascular, Santa Clara, California) in a 2:1 fashion. The original primary outcome was in-stent lumen loss at 9 months assessed by angiography and other secondary angiography endpoints. These results were previously published and demonstrated noninferiority of the Orsiro stent (3).
The objectives of the current BIOFLOW-II trial were to compare 5-year outcomes between Orsiro and X-EES (1). Primary endpoints were target lesion failure (TLF), its components, and stent thrombosis. The authors report that TLF occurred in 10.4% of Orsiro patients versus 12.7% of X-EES patients (p = 0.473), overall stent thrombosis occurred in 0.7% versus 2.8% (p = 0.088), and definite stent thrombosis in 0% versus 0.7% (p = 0.341). Post hoc analysis was performed in diabetic patients (n = 128) and vessels ≤2.75 mm (n = 259). Among diabetic patients, the Orsiro group had numerically more target lesion revascularizations (13.5% vs. 4.5%; p = 0.138), but fewer cardiac deaths (1.3% vs. 6.9%; p = 0.089) and stent thrombosis (0% vs. 6.9%; p = 0.039). In small vessels, the Orsiro group had a significantly lower 5-year mortality (3.7% vs. 11.3%; p = 0.022).
The authors concluded that at 5 years, the BP-DES Orsiro stent continued to demonstrate low TLF rates comparable to the DP-DES X-EES. The absence of definite stent thrombosis was the most striking finding. The authors speculate that these excellent long-term outcomes are a reflection on the ultrathin stent struts, passive silicon carbide stent coating that reduces ion release and prevents corrosive processes, and the slower biodegradable polymer.
Findings in the BIOFLOW-V trial reaffirm the good profile of the Orsiro stent in which the 12-month TLF rate was 6.0% compared with X-EES of 10.0% (p = 0.039) (4).
Nevertheless, long-term outcomes in novel stent technology are extremely important. The leading BP-DES competitors to the Orsiro stent that have 5-year outcomes are BioMatrix Flex (Biosensors, Newport Beach, California), Synergy (Boston Scientific, Marlborough, Massachusetts), and Nobori (Terumo, Tokyo, Japan).
The LEADERS (Limus Eluted From A Durable Versus ERodable Stent Coating) trial reported 5-year outcomes with the BioMatrix Flex stent compared with the Cypher SELECT stent (Cordis, Miami Lakes, Florida). The BioMatrix Flex stent consists of 316L-stainless steel with a 120 um thickness. It has a polylactic acid abluminal polymer degradable at 9 months. The antiproliferative agent is biolimus, which is eluted by 6 months (2). The TLF rate was similar for both stents, and the definite or probable ST rate was 3.6% for BioMatrix Flex and 5.2% for Cypher SELECT (5).
EVOLVE (A Prospective Randomized Multicenter Single-Blind Noninferiority Trial to Assess the Safety and Performance of the Evolution Everolimus-Eluting Monorail Coronary Stent System [Evolution Stent System] for the Treatment of a De Novo Atherosclerotic Lesion) reported 5-year outcomes with the Synergy stent compared with a DP-DES EES. The Synergy stent consists of 74-μm-thick platinum chromium struts. It has a poly(lactic-co-glycolic acid) abluminal polymer which degrades by 4 months. The antiproliferative agent is everolimus, which is eluted by 3 months (2). TLF was 5.5% in the Synergy group compared with 7.2% in the EES group. There was no definite or probable stent thrombosis in either group (6).
The COMPARE II (Abluminal Biodegradable Polymer Everolimus-Eluting Stent Versus Durable Polymer Everolimus-Eluting Stent) trial reported 5-year outcomes with the Nobori stent compared with the X-EES stent. The Nobori stent consists of 316-L stainless steel with 125-μm thickness. It has a polylactic acid abluminal polymer that degrades by 9 months. The antiproliferative agent is biolimus, which is eluted by 6 months (2). The TLF was similar for both groups. Definite or probable stent thrombosis was 1.5% in the Nobori stent and 0.9% in the X-EES group (7). SORT-OUT VII (Scandinavian Organization for Randomized Trials With Clinical OUTcome) randomized over 2,500 patients to the Orsiro stent or the Nobori stent. The definite stent thrombosis rate was 0.4% with Orsiro and 1.2% with Nobori (p = 0.03) (8).
There are other emerging BP-DES platforms and additional novel hybrids in development that go beyond the scope of this editorial commentary. Discussion of these other platforms would be best saved for a comprehensive state-of-the art review. Although early results always seem promising, long-term outcomes are essential.
In summary, long-term outcomes do matter with novel stent technology. The 5-year data for the Orsiro stent appear very promising, and it may turn out to be a workhorse stent. The ultrathin stent struts in small and intermediate-diameter vessels allow treatment of smaller arteries and perhaps less chance of stent thrombosis. The passive silicon carbide stent coating may reduce ion release and prevent corrosive processes. One would think that the circumferential polymer and slow degradation rate may not be as effective as an abluminal polymer and fast elution. But the low late stent thrombosis rates with Orsiro are impressive. Future studies might focus on shorter duration of dual antiplatelet therapy.
At present, the Orsiro, BioMatrix, and Nobori stents are not approved for clinical use in the United States. There is speculation that the Orsiro stent may be approved by the U.S. Food and Drug Administration by the end of this year. The Synergy stent has been approved for clinical use in the United States. Synergy has a very good technical and clinical profile, but long-term results and the potential to reduce the duration of dual antiplatelet therapy will determine its use in contemporary practice. In the meantime, the concept of BP-DES offers great promise and may be the “hybrid” solution to long-term problems with bare-metal stents, DP-DES, and bioresorbable scaffolds. The journey of novel stent development and long-term outcome assessment continues.
↵∗ Editorials published in JACC: Cardiovascular Interventions reflect the views of the authors and do not necessarily represent the views of JACC: Cardiovascular Interventions or the American College of Cardiology.
Dr. Kutcher has received Interventional Cardiology Fellowship Training Grant support from the Abbott Fund, administered by Rockefeller Philanthropy Advisors.
- 2018 American College of Cardiology Foundation
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