Author + information
- Received June 15, 2015
- Revision received September 23, 2015
- Accepted September 24, 2015
- Published online January 11, 2016.
- Ricardo A. Costa, MD, PhD∗,†∗ (, )
- Alexandre Abizaid, MD, PhD∗,†,
- Roxana Mehran, MD‡,
- Joachim Schofer, MD§,
- Gerhard C. Schuler, MD‖,
- Karl E. Hauptmann, MD¶,
- Marco A. Magalhães, MD†,
- Helen Parise, ScD‡,
- Eberhard Grube, MD#,
- BioFreedom FIM Clinical Trial Investigators
- ∗Institute Dante Pazzanese of Cardiology, São Paulo, Brazil
- †Cardiovascular Research Center, São Paulo, Brazil
- ‡Cardiovascular Research Foundation, New York, New York
- §Medical Care Center, Hamburg University Cardiovascular Center, Hamburg, Germany
- ‖Herzzentrum Leipzig GmbH, Leipzig, Germany
- ¶Krankenhaus der Barmherzigen Brüder, Trier, Germany
- #University of Bonn, Bonn, Germany
- ↵∗Reprint requests and correspondence:
Dr. Ricardo A. Costa, Department of Invasive Cardiology, Institute Dante Pazzanese of Cardiology/Cardiovascular Research Center, Rua Dr. Altolfo Araújo, 521–Vila Mariana, São Paulo, SP, Brazil 04012-070.
Objectives The purpose of this study was to evaluate the efficacy and long-term outcomes of a novel polymer/carrier-free drug-coated stent (DCS) in patients with de novo coronary lesions.
Background The BioFreedom (BFD) DCS incorporates a low-profile, stainless-steel platform, with a surface that has been modified to create a selectively microstructured abluminal surface that allows adhesion and further release of Biolimus A9 (Biosensors Europe SA, Morges, Switzerland).
Methods A total of 182 patients (183 lesions) were randomized into a 1:1:1 ratio for treatment with BFD “standard dose” (BFD) or BFD “low dose” (BFD-LD) versus first-generation paclitaxel-eluting stents (PES) at 4 sites in Germany.
Results Baseline and procedural characteristics were well matched. At 4-month angiographic follow-up (Cohort 1, n = 75), in-stent late lumen loss (LLL) was significantly lower with BFD and BFD-LD versus PES (0.08 and 0.12 mm vs. 0.37 mm, respectively; p < 0.0001 for BFD vs. PES, and p = 0.002 for BFD-LD vs. PES). At 12 months (Cohort 2, n = 107), in-stent LLL (primary endpoint) was 0.17 mm in BFD versus 0.35 mm in PES (p = 0.001 for noninferiority; p = 0.11 for superiority); however, the BFD-LD (0.22 mm) did not reach noninferiority (p = 0.21). At 5 years (175 of 182), there were no significant differences in major adverse cardiac events (23.8%, 26.4%, and 20.3%) and clinically indicated target lesion revascularization (10.8%, 13.4%, and 10.2%) for BFD, BFD-LD, and PES, respectively; also, there was no definite/probable stent thrombosis reported.
Conclusions The BFD, but not the BFD-LD, demonstrated noninferiority versus PES in terms of in-stent LLL, a surrogate of neointimal hyperplasia, at 12-month follow-up. At 5 years, clinical event rates were similar, without occurrence of stent thrombosis in all groups. (BioFreedom FIM Clinical Trial; NCT01172119)
- coronary artery disease
- drug-coated stent(s)
- percutaneous coronary intervention
Nonpolymeric drug-coated stents (DCS) have been introduced as an alternative to polymeric drug-eluting stents (DES), as previous studies investigating the biocompatibility of drug carriers—particularly durable polymers used in first-generation DES—had demonstrated negative effects of these components on vessel healing due to chronic inflammation and local toxicity, which could lead to proliferative and thrombogenic responses over time (1–6). In addition, the safety of current DES systems appears to be dependent on relatively long (≥6 months) dual antiplatelet therapy (DAPT) (7,8), a fact that may limit their use on a significant proportion of patients with adherence restraints, such as those at high risk for bleeding (9). However, the absence of a drug carrier has also been associated with lesser efficacy at inhibiting neointimal hyperplasia (NIH), most probably due to insufficient and/or uncontrolled drug delivery at the target coronary site (10–13).
BA9 (biolimus), a 31-membered triene macrolide lactone derivative of sirolimus, is a potent antiproliferative agent that has been developed for vascular applications, specifically for DES (14). Overall, biolimus has consistently demonstrated high efficacy at inhibiting NIH, as well as sustained safety when delivered via a biodegradable polymer DES in multiple clinical scenarios (15–17). Still, the effect of biolimus released from a polymer/carrier-free DCS system in human coronary arteries is yet to be determined. Hence, the purpose of this analysis was to report the first-in-man (FIM) evaluation of a new polymer-free biolimus-coated stent in the treatment of de novo coronary lesions. The study hypothesis was that a polymer-free biolimus release via a microstructured stent surface (18) could be as effective in reducing NIH as compared with a first-generation paclitaxel-eluting stent (PES) in diseased coronary vessels.
Study design and patient population
The BioFreedom FIM clinical trial was a prospective, randomized, single-blinded, multicenter feasibility study designed to investigate the performance, safety, and efficacy of the novel polymer-free BioFreedom biolimus-coated stents (Biosensors Europe SA, Morges, Switzerland) versus the Taxus Liberté PES (Boston Scientific, Natick, Massachusetts) in the treatment of coronary lesions. The BioFreedom device (BFD) was tested with 2 drug formulations: BFD “standard dose” and BFD “low dose” (BFD-LD). Inclusion criteria were: age ≥18 years; symptoms of stable or unstable angina, and/or presence of a positive functional test for ischemia; single de novo target lesion ≤14 mm in length, with stenosis 50% to 99%, in native coronary vessel 2.5 to 3.0 mm in diameter; acceptable candidate for coronary artery bypass graft surgery; and agreement to undergo all protocol follow-ups (FUs), including 1 angiographic re-evaluation. Key exclusion criteria were: myocardial infarction <72 h; left main, ostial location; moderate or severe calcification, as visible by fluoroscopy; target lesion involving a side branch >2.0 mm in diameter; thrombus; documented left ventricular ejection fraction <30% assessed within 6 months prior to procedure by echocardiography, during previous angiography, or as measured during pre-procedure angiography; known hypersensitivity or contraindication to antithrombotic therapy; and concurrent medical condition with life expectancy <18 months.
The study complied with the Declaration of Helsinki regarding investigation in humans, followed ISO-14155:2003, and was approved by the local ethics committees at the participant institutions. All patients provided written informed consent prior to procedure.
The study device has been detailed elsewhere (18). In brief, it incorporates a 316L stainless-steel platform, which has been modified with a proprietary surface treatment resulting in a selectively microstructured abluminal surface (Figure 1). The selectively microstructured surface allows adhesion of the antiproliferative agent (biolimus) to the abluminal surface of the stent without a polymer or binder. The drug dose for the BFD device was 15.6 μg/mm of stent length, whereas a half-dose (7.8 μg/mm of stent length) was used for BFD-LD. As for release kinetics, approximately 90% of biolimus was released from the stent <48 h after implant, irrespectively of dose formulation, with the remaining being released in up to 28 days.
Randomization and procedure
Eligible patients were randomized in a 1:1:1 ratio for treatment with BFD, BFD-LD, and PES. The first subset of randomized patients (Cohort 1) was assigned to 4-month angiographic FU, as the intention was to have an early assessment of efficacy for a novel DCS with boost drug release. The second subset of randomized patients (Cohort 2) was assigned to 12-month angiographic FU. Percutaneous coronary intervention was performed according to standard guidelines. Lesion pre-dilation was recommended by protocol; only 1 stent was allowed per target lesion, even though additional stent(s) (same as group allocation) could be used in bailout situations. The BioFreedom stents were available in 2.5 and 3.0 mm diameters and 14 and 18 mm lengths; PES were 2.5, 2.75, and 3.0 mm in diameter, and 12, 16, and 20 mm in length. Multivessel percutaneous coronary intervention at index procedure including treatment of a nontarget lesion in a nontarget vessel was allowed, given that the nontarget lesion had to be successfully treated first, with any nonstudy device, at the operator’s discretion. At post-procedure, DAPT was prescribed for at least 6 months.
Endpoints and data management
The primary endpoint was in-stent late lumen loss (LLL), as determined by independent quantitative coronary angiography (QCA) analysis, at 12-month angiographic FU (Cohort 2). Key secondary endpoints included: in-stent LLL at 4 months (Cohort 1); major adverse cardiac events, definite or probable stent thrombosis (ST) (19); clinically-driven target-lesion revascularization (TLR) and clinically-driven target-vessel revascularization at hospital discharge and at 30-day, 4-month, 12-month, and yearly up to 5-year FU; angiographic binary restenosis at 4- (Cohort 1) and 12-month (Cohort 2) FU; and lesion and procedural success. Data coordination and management, statistical analysis, and unblinding of the data were performed by an independent data coordinating center (Cardiovascular Research Foundation, New York, New York). Primary data collection was performed at each clinical site following standard procedures including source verification, electronic completion of individual Case Report Forms, physical monitoring, and remittance of proper source-documentation. By protocol, clinical FU consisting of medical visits were scheduled at 1-, 4-, and 12-month and yearly up to 5-year FU. Full definitions and details of the study organization are provided in the Online Appendix.
Serial coronary angiographic studies were obtained after intracoronary administration of nitroglycerin (100 to 200 μg, unless contraindicated) in 2 orthogonal matching views at pre-procedure, post-procedure and FU. Angiographic analysis was performed offline by experienced operators blinded to group allocation, procedural data, and clinical outcomes at an independent core laboratory (Cardiovascular Research Center, São Paulo, Brazil). Quantitative analysis was performed with validated 2-dimensional software for QCA analysis (QAngio XA version 7.2, Medis, Leiden, the Netherlands) (Online Appendix). LLL was the change in minimum lumen diameter from the post-stent implantation angiogram to FU; binary restenosis was defined as stenosis ≥50% at angiographic FU. QCA measurements were reported: “in-stent,” within the stented segment; “in-segment,” spanning the stented segment plus the 5-mm proximal and distal peristent areas; and at 5-mm proximal and distal peristent edges (outside of the stent).
The sample size calculation for the BioFreedom FIM trial was based on the expected in-stent LLL results at 12-month angiographic FU (Cohort 2), given that this randomized trial would measure the noninferiority of the BFD (“standard-dose”) group compared with the PES group. The null hypothesis (Ho) for the primary endpoint was that the BFD group would have a mean in-stent LLL at 12 months that exceeds that of the PES group by at least a pre-specified margin of δ (delta), that is, 0.24 mm. The alternative hypothesis (Ha) was that the BFD group would have in-stent LLL at 12 months that is lower than the PES group plus δ. Therefore, rejection of the null hypothesis would indicate that the BFD group is noninferior to the PES group in regard to 12-month in-stent LLL. The null and alternative hypotheses of interest are the following:
• Ho: μ BFD ≥ μ Taxus + δ;
• Ha: μ BFD < μ Taxus + δ;
where μ BFD is the mean in-stent LLL for the BFD arm, and μ PES is the mean in-stent LLL for the PES active control arm. The pre-specified margin (delta of 0.24 mm) was considered because it yields less than one-half of the estimated SD of in-stent LLL (0.5 mm), as estimated from prior studies (20). In addition, because previous data suggest that biolimus-eluting stents perform better than PES, it was assumed that the in-stent LLL at 12-month FU for the BFD group would be at least 0.12 mm lower than the PES group (15,16,18,20). Hence, a minimum sample size of 32 patients in each study arm of Cohort 2 would give >80% power at 1-sided α (alpha) of 0.025 to reject the null hypothesis in favor of noninferiority of the BFD arm relative to the PES arm. Anticipating up to 10% lost to angiographic FU, the minimal sample size per randomized group in Cohort 2 was increased by approximately 10% (35 patients). As for Cohort 1, there were no formal statistical assumptions as the intention was to have an early evaluation of efficacy at 4-month angiographic FU.
Categorical variables are expressed as numbers and percentages (or frequencies) of the total. Continuous variables are expressed as mean ± SD or median (interquartile range) when appropriate, on the basis of their distribution pattern. Statistical comparisons were conducted between BFD and PES and between BFD-LD and PES. Categorical variables were compared with chi-square or Fisher exact tests. Continuous variables were compared for superiority with the Student t test if normality was present or Wilcoxon rank sum test in case of non-normality. Kaplan-Meier event rates were compared using the log-rank test. Hazard ratios (HRs) with 95% confidence intervals were calculated using Cox proportional hazards regression. All statistical analyses were performed using SAS software version 8.2 or higher (SAS Institute Inc., Cary, North Carolina). A p value <0.05 was considered statistically significant.
A total of 182 patients were enrolled between September 2008 and June 2009 at 4 sites in Germany; the first 75 randomized patients were allocated in Cohort 1, and the subsequent 107 randomized patients were allocated in Cohort 2. The majority of patients (92%) underwent angiographic FU at their pre-assigned timeframe—either 4 or 12 months—and 98.9% (180 of 182) completed 12-month clinical FU (Figure 2). Considering the overall population, baseline characteristics were well matched between the groups (Tables 1 and 2). All lesions were successfully treated, and procedural success was achieved in all but 1 patient in the BFD-LD group (Online Table 1).
Pre- and post-procedure QCA results were similar in the overall study population (Table 2), as well as in Cohorts 1 and 2 (Online Table 2). At 4-month FU (Cohort 1), in-stent LLL (secondary endpoint) was significantly lower with BFD and BFD-LD versus PES (0.08 and 0.12 mm vs. 0.37 mm, respectively; p < 0.0001 for BFD vs. PES, p = 0.002 for BFD-LD vs. PES) (Table 3). There were no cases of in-stent restenosis in both the BFD and BFD-LD groups; conversely, 9.1% (2 of 22) presented with in-stent restenosis in PES. Moreover, focal edge restenosis was found in 1 case in each group. The primary outcome was assessed in Cohort 2 (Table 3), and in-stent LLL was 0.17 mm in BFD versus 0.35 mm in PES (p = 0.001 for noninferiority; p = 0.11 for superiority); however, in-stent LLL with BFD-LD (0.22 mm) did not reach significance in terms of noninferiority against PES (p = 0.21) (Figure 3). Cumulative frequency distribution curves for in-stent minimum lumen diameter are shown in Figure 4. In addition, in-stent restenosis rates were 6.7% (2 of 30) and 8.6% (3 of 35) versus 3.2% (1 of 31), whereas in-segment restenosis was 6.7% (2 of 30) and 14.3% (5 of 35) versus 9.7% (3 of 31), for the BFD, BFD-LD, and PES groups, respectively (all p values nonsignificant).
Kaplan-Meier estimates and occurrence curves for the composite and individual clinical endpoints are reported in Table 4 and Figure 5. Between 1 and 5 years (Online Table 3), clinically driven TLR, associated with angiographic restenosis within the treated segment, was found in 2 of 5 cases in BFD, 2 of 4 in BFD-LD, and 1 of 3 in PES. The other cases of TLR evidenced patent stents, but significant stenoses within the coronary segments adjacent to the target lesion site (stent +5-mm proximal/distal edges). Considering any TLR, event rates were 10.8% (n = 6) in BFD and 15.1% (n = 9) in BFD-LD versus 11.9% (n = 7) in PES (all p values nonsignificant). Overall, there were no cases of Academic Research Consortium definite or probable ST in any group.
In the current analysis, we tested the proof of concept that a polymer/carrier-free biolimus release via a microstructured stent surface could be effective in reducing NIH as compared with PES; results were positive with BFD, but not with BFD-LD. In addition, there were similar event rates up to 5 years and no safety concerns, including absence of Academic Research Consortium definite or probable ST in all groups. Most of the rationale for developing nonpolymeric DCS has been based on previous observations that linked synthetic polymers used in first-generation DES with persistent local inflammatory and toxic responses, which could lead to delayed (or lack of) vascular healing, hypersensitivity reactions, endothelial dysfunction, and even neoatherosclerosis; all phenomena that have been associated with late and very late recurrences including ST (1–6,21–23). Overall, durable polymers used in first-generation DES were associated with suboptimal biocompatibility and mechanical complications; consequently, second-generation DES have incorporated lower-profile components with thrombus-resistant properties; also, DES with biodegradable polymers have shown improved long-term safety compared with DES with durable polymers (1–6,17,21–26). Nonetheless, despite clinical superiority of new-generation DES over first-generation DES, late and very late events may still occur (17,27). Hence, nonpolymer-based DCS could offer, at least theoretically, additional advantages such as: avoiding problems related to temporary or permanent polymeric residue; optimizing vascular healing; maintaining stent surface integrity (as opposed to webbing/delamination phenomenon seen with polymeric devices); and shortening DAPT post-stent implantation, reducing bleeding (without compromising safety) while maintaining efficacy at inhibiting NIH. The BioFreedom DCS technology was primarily conceived with a dose of biolimus identical to the reference dose applied in the BioMatrix biolimus-eluting stent (Biosensors Europe SA, Morges, Switzerland) with a biodegradable polymer, as this device has demonstrated high efficacy and sustained safety in multiple clinical scenarios (15–17). Yet, due to the high lipophilicity property of Biolimus (∼10× greater than sirolimus) (14), it was rationalized that a “lower dose” of biolimus could be as efficacious and safe as the “standard drug dose,” with potential additional advantages in terms of minimizing local inflammatory response (due to less drug load) and providing faster and enhanced vessel healing. Such assumptions were supported by prior pharmacokinetics analysis with biolimus (14) and pre-clinical studies with BioFreedom stents (18), which demonstrated high efficacy in reducing NIH, optimal vessel healing, and minimal local inflammatory response with both BFD and BFD-LD. In the current analysis, the BFD group met the primary outcome of noninferiority in terms of in-stent LLL at 12-month angiographic FU (p < 0.001), with a statistically nonsignificant trend toward superiority (p = 0.11) versus the PES group. As for clinical events, there were no significant differences, and most recurrences after 1 year appeared to be related to coronary artery disease progression occurring in coronary segments other than the treated site. Of note is the fact that the BioFreedom FIM trial was not designed, sized, or statistically powered to demonstrate superiority of the study groups versus the active control group in terms of LLL or any other angiographic or clinical endpoint. Nevertheless, 12-month in-stent LLL with BFD was relatively low (0.17 mm) and was comparable to the most effective DES systems tested to date (15,24,25,28). Interestingly, the BFD-LD group did not meet the primary endpoint of noninferiority versus PES (p = 0.21); in addition, it showed numerically higher rates of angiographic and clinical restenosis (Table 4), thus suggesting inferior efficacy at inhibiting NIH. On the basis of these results, the BioFreedom clinical program was continued with the BFD stent only, as proof of concept was not demonstrated with BFD-LD.
Uncontrolled or boost drug release has been associated with poor efficacy and DCS failure (10–13); however, drug dose and pharmacodynamics may play an important role. In the DELIVER (The RX ACHIEVE Drug-Eluting Coronary Stent System [CSS] In the Treatment of Patients with De NoVo NativE CoronaRy Lesions) trial, only a marginal benefit in terms of in-stent LLL was observed at 8-month FU with the polymer-free paclitaxel-coated stent versus the uncoated control stent (0.81 mm vs. 0.98 mm; p = 0.003, respectively); however, this difference did not translate into significant reductions in binary restenosis or TLR rates. By that time, it was estimated that up to 40% of the drug was lost during stent delivery; also, release kinetics was considered “too fast” (within days to weeks) (10). On the contrary, the Taxus PES with durable polymer (used as active control group in our study) had a much slower drug release (<10% in 30 days), with approximately 67% less drug compared with the DCS used in the DELIVER trial; yet, in-stent LLL in the TAXUS-IV trial was considerably lower (0.37 mm), despite identical drug (paclitaxel) (20). Similarly, polymer-free sirolimus-eluting stents seem to perform worse in terms of efficacy compared with polymer-based sirolimus-eluting stents (12). Both BFD and BFD-LD shared identical stent design and release kinetics, but differed on drug dosage (BFD-LD with one-half dose of BFD). Therefore, we may speculate that the main mechanism associated with the negative results in terms of efficacy found with BFD-LD is insufficient drug amount, rather than release kinetics. Furthermore, the BFD DCS and the BioMatrix DES have completely different drug release kinetics (BioMatrix: ∼70% in 30 days; BioFreedom: ∼90% in 48 h); still, in-stent LLL appears to be similar, despite boost release with BFD (15,16,18). There are a few possibilities to explain these findings. The innovative modified surface technology creating a selectively microstructured textile reservoir in BioFreedom appears to be effective at holding and carrying the drug to the target site, where it dissolves (18). Moreover, biolimus may offer significant advantages compared with other “limus” agents, as it may improve pharmacokinetics due to its high lipophilicity and, consequently, optimize bioavailability with rapid distribution into the arterial wall during the initial hours after stent implant; this allows achievement of faster therapeutic concentrations and extended duration of treatment effect (14,18), which may counterbalance the potentially negative effects of boost release.
First, we studied relatively simple and discrete lesions; thus, caution should be used before generalizing our results to patients with more complex disease. Second, PES represents a somewhat outdated DES technology, which has demonstrated to be inferior to current-generation DES (27); however, the reasons we chose this active comparator were: 1) it was still largely used at the time of protocol design and enrollment start (29,30); 2) there was robust evidence, without major concerns in terms of safety and clinical efficacy by that time (29–31); 3) it had been used as control therapy in multiple other studies; and 4) on the basis of its historical LLL (0.37 mm) (20), it was thought to be the right comparator considering a noninferiority study design and the assumptions made for the primary endpoint. Third, even though there were no significant differences in clinical outcomes and absence of definite/probable ST up to 5 years, no conclusions regarding safety and efficacy can be made, as the BioFreedom FIM trial was not statistically powered to demonstrate noninferiority or superiority in clinical endpoints; therefore, future large-scale studies are needed to demonstrate the clinical implications of the BFD stent, particularly in comparison with newer-generation DES. Specifically, due to its design and concept, the BFD stent may offer less dependence on prolonged DAPT than polymer-coated DES (18), and to test this hypothesis, the 2,456 patient randomized LEADERS FREE trial (NCT01623180) is currently ongoing (32). On the basis of our findings, we may speculate that BFD is likely to improve clinical efficacy against uncoated stents, but the implications regarding safety in such complex populations as expected in this trial are yet to be determined.
The polymer-free BioFreedom biolimus-coated stents with a standard dose (BFD) demonstrated high efficacy in inhibiting NIH at 4- and 12-month angiographic re-evaluations and were noninferior to the PES in terms of in-stent LLL, a surrogate of NIH, at 12-month FU. In addition, there were no safety concerns up to 5 years, including similar rates of major adverse cardiac events and absence of definite or probable ST in all groups.
WHAT IS KNOWN? Nonpolymeric DCS have been introduced as an alternative to polymeric DES to avoid problems related to temporary or permanent polymeric residue that could lead to chronic inflammation and local toxicity; however, the absence of a drug carrier had been associated with lesser efficacy at inhibiting NIH.
WHAT IS NEW? In the BioFreedom first-in-man trial, the proof of concept that a polymer-free BA9 (biolimus) release via a microstructured stent surface could be as effective in reducing NIH as a first-generation PES was demonstrated, as the BioFreedom drug-coated stent with a “standard dose” of biolimus (15.6 μg/mm of stent length) was significantly noninferior in terms of in-stent late lumen loss, a surrogate of NIH, as compared with the PES active control group at 12-month angiographic follow-up (0.17 mm vs. 0.35 mm, respectively; p < 0.001).
WHAT IS NEXT? Due to its design and concept, the BioFreedom drug-coated stent may offer less dependence on prolonged dual antiplatelet therapy than polymer-coated DES while maintaining efficacy; thus, it may be suitable for those who are at high risk for bleeding. The ongoing LEADERS FREE trial is investigating the clinical effect of the BioFreedom technology versus uncoated stents in complex patients at high risk for bleeding receiving short-term (1-month) dual antiplatelet therapy; furthermore, future large-scale studies are needed to investigate BioFreedom’s clinical implications in comparison with newer-generation DES.
For supplemental methods and tables, please see the online version of this article.
The study was funded by Biosensors Europe SA. Dr. Costa has received speaker’s fees from Biosensors Europe SA, Medtronic, and Daiichi-Sankyo; and has served as a consultant for Biosensors Europe SA. Dr. Abizaid has received research grants from Medtronic, Boston Scientific, Abbott Vascular, Biosensors, and Elixir Medical. Dr. Mehran has received institutional research grants from Bristol-Myers Squibb/Sanofi Pharmaceuticals, Eli Lilly, AstraZeneca, The Medicines Company, and Lilly/Daiichi-Sankyo; and has received consultant/advisory board fees from Abbott Vascular, AstraZeneca, Bayer, CSL Behring, Boston Scientific, Covidien, The Medicines Company, Merck, Osprey Medical, Regado Biosciences, Sanofi-Aventis, Watermark Research Partners, and Janssen Pharmaceuticals/Johnson & Johnson. Dr. Schofer has received institutional research grants from Biosensors Europe SA. Dr. Grube has received consulting fees/honoraria from Biosensors Europe SA, Boston Scientific, and Abbott Vascular. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.
- Abbreviations and Acronyms
- drug-coated stent(s)
- drug-eluting stent(s)
- “low dose”
- late lumen loss
- neointimal hyperplasia
- paclitaxel-eluting stent(s)
- target lesion revascularization
- Received June 15, 2015.
- Revision received September 23, 2015.
- Accepted September 24, 2015.
- 2016 American College of Cardiology Foundation
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