Author + information
- Received September 23, 2015
- Revision received December 3, 2015
- Accepted December 7, 2015
- Published online April 11, 2016.
- Gennaro Giustino, MDa,
- Usman Baber, MD, MSca,
- Melissa Aquino, MSca,
- Samantha Sartori, PhDa,
- Gregg W. Stone, MDb,
- Martin B. Leon, MDb,
- Philippe Genereux, MDc,d,e,
- George D. Dangas, MD, PhDa,
- Jaya Chandrasekhar, MBBSa,
- Takeshi Kimura, MDf,
- Olga Salianskia,
- Giulio G. Stefanini, MD, PhDg,
- P. Gabriel Steg, MD, PhDh,
- Stephan Windecker, MD, PhDi,
- William Wijns, MDj,
- Patrick W. Serruys, MD, PhDk,
- Marco Valgimigli, MD, PhDl,
- Marie-Claude Morice, MDm,
- Edoardo Camenzind, MDn,
- Giora Weisz, MDb,o,
- Pieter C. Smits, MDp,
- David E. Kandzari, MDq,
- Soren Galatius, MDr,
- Clemens Von Birgelen, MDs,
- Robert Saporitos,
- Raban V. Jeger, MDt,
- Ghada W. Mikhail, MDu,
- Dipti Itchhaporia, MDv,
- Laxmi Mehta, MDw,
- Rebecca Ortega, MHAx,
- Hyo-Soo Kim, MDy,
- Adnan Kastrati, MDz,
- Alaide Chieffo, MDaa and
- Roxana Mehran, MDa,∗ ()
- aThe Zena and Michael A. Wiener Cardiovascular Institute, Interventional Cardiovascular Research and Clinical Trials Center, Icahn School of Medicine at Mount Sinai, New York, New York
- bDivision of Cardiology, Columbia University Medical Center, New York, New York
- cCardiovascular Research Foundation, New York, New York
- dDivision of Cardiology, Columbia University Medical Center, New York, New York
- eDivision of Cardiology, Hôpital du Sacré-Coeur de Montréal, Montréal, Québec, Canada
- fDepartment of Cardiology, Kyoto University Graduate School of Medicine, Kyoto, Japan
- gDivision of Clinical and Interventional Cardiology, Humanitas Research Hospital, Rozzano, Milan, Italy
- hDépartement Hospitalo Universitaire Fibrose, Inflammation et REmodelage, Assistance Publique-Hôpitaux de Paris, Université Paris Diderot, INSERM U114, Paris, France
- iDepartment of Cardiology, Bern University Hospital, Bern, Switzerland
- jCardiovascular Center Aalst, Onze-Lieve-Vrouwziekenhuis Ziekenhuis, Aalst, Belgium
- kDepartment of Cardiology, Erasmus Medical Center, Rotterdam, the Netherlands
- lDepartment of Cardiology, University of Ferrara, Ferrara, Italy
- mDepartment of Cardiology and Cardiovascular Surgery, Institut Cardiovasculaire Paris Sud, France
- nDepartment of Cardiology, Institut Lorrain du Coeur et des Vaisseaux University Hospital Nancy, Brabois Vandoeuvre-lès-Nancy, France
- oDepartment of Cardiology, Shaare Zedek Medical Center, Jerusalem, Israel
- pDepartment of Cardiology, Maasstad Hospital, Rotterdam, the Netherlands
- qDepartment of Cardiology, Piedmont Heart Institute, Atlanta, Georgia
- rGentofte University Hospital, Hellerup, Denmark
- sDepartment of Cardiology, Thoraxcentrum Twente, Enschede, the Netherlands
- tDepartment of Cardiology, University Hospital Basel, Basel, Switzerland
- uDepartment of Cardiology, Imperial College Healthcare NHS Trust, London, United Kingdom
- vDepartment of Cardiology, Hoag Memorial Hospital Presbyterian, Newport Beach, California
- wDepartment of Cardiology, Ohio State University Medical Center, Columbus, Ohio
- xDuke Clinical Research Institute, Center for Educational Excellence, Durham, North Carolina
- yDepartment of Cardiology, Seoul National University Main Hospital, Seoul, Korea
- zDepartment of Cardiology, Herzzentrum, Munich, Germany
- aaCardiothoracic Department, San Raffaele Scientific Institute, Milan, Italy
- ↵∗Reprint requests and correspondence:
Dr. Roxana Mehran, The Zena and Michael A. Wiener Cardiovascular Institute, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, Box 1030, New York, New York 10029.
Objectives The purpose of this study was to investigate the safety and efficacy of new-generation drug-eluting stents (DES) versus early-generation DES in women undergoing complex percutaneous coronary intervention (CPCI).
Background Whether the benefits of new-generation DES are preserved in women undergoing complex percutaneous revascularization is unknown.
Methods We pooled patient-level data from women enrolled in 26 randomized trials of DES. Study population was categorized according to the presence or absence of CPCI, which was defined as the composite of total stent length >30 mm, ≥2 stents implanted, ≥2 lesions treated, or bifurcation lesion as target vessel. The primary endpoint was major adverse cardiovascular events (MACE) defined as a composite of all-cause mortality, myocardial infarction, or target lesion revascularization at 3 years of follow-up.
Results Of 10,241 women included in the pooled database, 4,629 (45%) underwent CPCI. Compared with non-CPCI, women who underwent CPCI had a higher 3-year risk of MACE (adjusted hazard ratio [HR]: 1.63; 95% confidence interval [CI]: 1.45 to 1.83; p < 0.0001). In women who underwent CPCI, use of new-generation DES was associated with significantly lower 3-year risk of MACE (adjusted HR: 0.81; 95% CI: 0.68 to 0.96), target lesion revascularization (adjusted HR: 0.74; 95% CI: 0.57 to 0.95), and definite or probable stent thrombosis (ST) (adjusted HR: 0.50; 95% CI: 0.30 to 0.83). The benefit of new-generation DES on efficacy and safety outcomes was uniform between CPCI and non-CPCI groups, without evidence of interaction. By landmark analysis, new-generation DES were associated with low rates (≤0.4%) of very-late ST irrespective of procedural complexity.
Conclusions Women undergoing CPCI remain at higher risk of adverse events. The long-term ischemic benefits of new-generation DES platforms are uniform among complex and non-complex percutaneous revascularization procedures in women.
Compared with bare-metal stents, the introduction of drug-eluting stents (DES) in clinical practice substantially improved the efficacy of percutaneous coronary intervention (PCI) by reducing the risk of in-stent restenosis and subsequent need of repeated revascularization (1). However, important safety concerns arose with DES, mainly due to a lower thrombotic safety, especially with their unrestricted and off-label use (2). In light of results from randomized controlled trials (RCTs), the U.S. Food and Drug Administration (FDA) gave on-label indications for DES use in simple, single, de novo coronary lesions in low-risk patients with stable coronary artery disease. However, currently most of the percutaneous coronary revascularizations with DES are performed in complex clinical and anatomical subsets of patients (3,4).
Anatomic and lesion complexity are known to influence the outcomes of PCI. Successful PCI of complex lesions and coronary artery anatomies require advanced procedural techniques, adjunctive devices, and experienced operators (5). Whereas men tend to have in general higher anatomic complexity, higher plaque burden, and more calcified lesions, women frequently have narrower, more tortuous vessels and more comorbidity at the time of coronary revascularization (6–8). Therefore, the success and complication rates of PCI in women might not follow the same patterns as those in men. In fact, women have been reported to experience a significantly higher risk of coronary perforations, dissections, and access-site complications (7,9,10). Additionally, female sex has been reported to be predictive of in-stent restenosis (11,12).
Women have been historically under-represented in RCTs that investigated the efficacy and safety of DES. In the 2011 FDA guidance document, sex disparities in RCTs investigating medical devices were recognized (13). In response to the recommendations provided by the FDA, the Society for Cardiovascular Angiography and Interventions’ Women in Innovation Initiative led to the creation and analysis of an individual patient-level pooled dataset from existing randomized trials of DES. The safety and efficacy of DES in women and their comparative effectiveness across clinical presentations has been already reported (14,15). In the present patient-level pooled analysis from RCTs of DES, we sought to evaluate the effect of procedural complexity on outcomes and whether the benefits of new-generation DES devices are preserved in this high-risk patient subset.
The rationale of the present patient-level pooled database, list of trials, analytic strategies, and pre-specified endpoints has been previously reported (15). Briefly, female participants from 26 RCTs evaluating safety and efficacy of DES were pooled. The full list and characteristics of the RCTs included in the present study are summarized in Online Tables 1 and 2. All of the included randomized controlled trials were performed between 2000 and 2013.
The study population was stratified into 2 categories on the basis of the complexity of PCI (Figure 1). Women who received a bare-metal stent were excluded from this analysis. Complex percutaneous coronary intervention (CPCI) was defined as the inclusion of 1 of the following characteristics: total stent length >30 mm, ≥2 stents implanted, ≥2 lesions treated, or bifurcation as target lesion.
All trials included in our analysis complied with the provisions of the Declaration of Helsinki, and the study protocols were approved by the institutional review board at each study center. All patients provided written informed consent for participation in each study.
The following DES have been included in the present analysis: sirolimus-eluting stents (Cypher and Cordis, Johnson & Johnson, Miami Lakes, Florida), paclitaxel-eluting stents (Taxus, Boston Scientific, Natick, Massachusetts), everolimus-eluting stents (Xience, Abbott Vascular, Santa Clara, California; Promus, Boston Scientific), zotarolimus-eluting stents (Endeavor, Medtronic, Santa Rosa, California; Resolute, Medtronic), biolimus-eluting stents with biodegradable polymer coating (Biomatrix, Biosensors, Newport Beach, California; Nobori, Terumo, Tokyo, Japan), and sirolimus-eluting stents with biodegradable polymer coating (Yukon, Translumina, Hechingen, Germany). Coronary stents used among trials were classified as: early-generation DES (including sirolimus- and paclitaxel-eluting stents) and new-generation DES (including everolimus- and zotarolimus-eluting stents with durable polymer and biolimus- and sirolimus-eluting stents with biodegradable polymer).
Study objectives and endpoint definitions
The objectives of the current study were: 1) to characterize the effect of procedural complexity in women undergoing percutaneous revascularization; and 2) to evaluate the safety and efficacy of new-generation compared with early-generation DES in women undergoing CPCI. The primary endpoint of the current study was the 3-year risk of major adverse cardiac events (MACE). MACE was defined as the composite of death, myocardial infarction (MI), or target lesion revascularization (TLR). Additional endpoints were the individual components of MACE, cardiac mortality, definite or probable stent thrombosis (ST), and the composite of all-cause mortality, MI, or definite or probable ST. The clinical endpoint definitions used across trials are described in Online Table 2.
All patient-level data were aggregated and combined as 1 dataset on a pre-specified extraction sheet. Baseline clinical, demographic, and procedural characteristics of the study groups were reported as mean ± SD for continuous variables and as proportions for categorical variables. Continuous variables were compared with the Student t test. Categorical variables were compared with the chi-square test. Cumulative event rates in the study groups were calculated with the Kaplan-Meier method and compared with the log-rank test. For these analyses, the total follow-up was defined as the time from index procedure until death, last follow-up date, or 3 years, whichever came first. Additionally, we performed Kaplan-Meier analyses in the landmark periods of 0 to 1 year and 1 to 3 years to evaluate the effect of DES generation on thrombotic endpoints at different time periods. The independent associations among CPCI, stent generation, and outcomes were assessed with the Cox proportional hazards models that included a frailty term (γ) to assess random effects in the trials. Frailties are the unmeasured factors that affect trial-specific baseline risk and are distributed as γ random variables with a mean of 1 and variance θ. The variance parameter was interpreted as a metric of heterogeneity in baseline risk between trials. The proportionality assumption was verified by means of Schoenfeld residual. In the adjusted analysis evaluating the effect of CPCI on outcomes, non-CPCI was the reference category. For the DES-level analysis, early-generation DES was the reference category. Age and baseline variables showing significant differences between groups were included as covariates in the multivariable model (including body mass index, family history of coronary artery disease (CAD), smoking, presentation with an acute coronary syndrome, number of stents per patient, and American College of Cardiology/American Heart Association type B2 or C lesions). For the DES-level analysis, the consistency of the effect of new-generation DES in women who did or did not undergo CPCI was evaluated with a formal interaction test. We performed an additional sensitivity analysis by grouping studies according to the type of MI definitions used in trials between old and new MI definitions and measured the interaction term with new- versus old-generation DES. We subsequently assessed the interaction between DES generation and procedural complexity in women enrolled in trials using new MI definitions. We judged p values <0.05 to be significant, and all analyses were done with SAS software version 9.4 (SAS Institute, Cary, North Carolina).
Of 10,241 women included in the pooled database, 4,629 (45%) underwent CPCI. Clinical characteristics according to PCI complexity are reported in Table 1. Women who underwent CPCI were older and had higher prevalence of diabetes mellitus, previous MI, and lower left ventricular ejection fraction. In terms of clinical presentation, women undergoing CPCI had more stable phenotypes and women without CPCI had higher prevalence of MI presentation. Angiographic and procedural data are reported in Table 1. Women who underwent CPCI had more complex CAD with higher prevalence of American College of Cardiology/American Heart Association type B2/C lesions, multivessel CAD, and moderate or severe coronary artery calcifications. New-generation DES were used in 59.3% and 61.4% in the non-CPCI and CPCI groups, respectively.
Effect of CPCI on 3-year clinical outcomes
Unadjusted and adjusted clinical outcomes according to complexity of PCI are reported in Figure 2 and Table 2. A significantly higher crude rate of MACE was observed in women with versus without CPCI (18.66% vs. 12.26%; p < 0.0001). Women with CPCI also had higher rates of all-cause mortality; cardiac mortality; MI; TLR; the composite of all-cause mortality or MI; and the composite of all-cause mortality, ST, or MI. Following multivariable adjustment, complex PCI was independently associated with a higher risk of MACE (adjusted hazard ratio [HR]: 1.63; 95% confidence interval [CI]: 1.45 to 1.83; p < 0.0001); all-cause mortality; cardiac mortality; MI; TLR; the composite of all-cause mortality or MI; and the composite of all-cause mortality, MI, or ST. CPCI was not independently associated with a higher risk of ST.
Early- versus new-generation DES in women undergoing CPCI
The 3-year outcomes according to PCI complexity and DES generation are reported in Figure 3 and Table 3. In women who underwent CPCI, the use of new-generation DES was associated with a significantly lower risk of MACE at 3 years (adjusted HR: 0.81; 95% CI: 0.68 to 0.96) compared with early-generation DES (Table 3). As well, compared with early-generation DES, use of new-generation devices was associated with a significant benefit in all-cause mortality (adjusted HR: 0.72; 95% CI: 0.53 to 0.97), TLR (adjusted HR: 0.74; 95% CI: 0.57 to 0.95), definite/probable ST (adjusted HR: 0.50; 95% CI: 0.30 to 0.83), and the composite of all-cause mortality or MI (adjusted HR: 0.78; 95% CI: 0.64 to 0.96). The magnitude and direction of the effect of new-generation DES on outcomes was uniform between CPCI and non-CPCI women, without evidence of interaction for the studied endpoints. The proportionality assumption was not violated for the studied endpoints. The results were consistent following exclusion of trials that implemented old MI definitions (as defined in Online Table 2).
Landmark analysis in the time windows of 0 to 1 year and 1 to 3 years is illustrated in Figure 4. The benefits of new-generation DES on MACE (Figure 4A); the composite of death, MI, or ST (Figure 4B); and definite or probable ST (Figure 4C) were more apparent between 1 and 3 years, rather than within the first year. In particular, whereas the rates of ST were overall similar within the first year among groups, in the very late period, new-generation DES were associated with significantly lower rates (≤4%) of ST in both CPCI and non-CPCI; there were no differences in very-late ST rates between CPCI and non-CPCI with new-generation DES.
To the best of our knowledge, this is the first large report with patient-level data from RCTs investigating the safety and efficacy of early- versus new-generation DES in women according to PCI complexity. The main findings of our study are: 1) procedural complexity is associated with increased long-term risk of MACE and mortality after DES implantation in women; 2) compared with early-generation DES, use of new-generation DES in women is associated with significantly improved safety and efficacy, irrespective of procedural complexity; in particular, in women undergoing CPCI, antithrombotic properties of new-generation devices are evident through the early, late, and very-late period after PCI; and 3) irrespective of procedural complexity, new-generation DES were associated with exceedingly low rates of very-late ST (≤0.4%) at 3 years of follow-up.
Several observational studies and meta-analyses suggested a significant attenuation of the benefit of off-label DES implantation compared with on-label use or bare-metal stents (4,16–18). However, these studies were either observational in nature or had insufficient power to allow any definitive conclusions regarding the safety and efficacy of DES, especially in high-risk female patient subsets. Considering the sex-specific substantial gap in knowledge, the present pooled database of female patients from 26 RCTs of DES was created (13,14). In the present analysis, we sought to investigate the effect of procedural complexity on clinical outcomes in women undergoing PCI with DES and to evaluate the benefits of new-generation DES according to procedural complexity.
Outcomes in women undergoing CPCI
CAD complexity is a well-known predictor of adverse outcomes and significantly influences the comparative effectiveness of invasive coronary artery revascularization strategies (19). The SYNTAX (Synergy Between PCI With Taxus and Cardiac Surgery) score is a semiquantitative tool developed to characterize and quantify the extent of CAD to guide revascularization decision-making. Previously, both the baseline CAD complexity (higher SYNTAX score) and the residual CAD complexity or degree of incomplete revascularization (the residual SYNTAX score) have been demonstrated to be associated with adverse mid- to long-term outcomes after PCI (20–23). Instead, the effect of procedural complexity (which may or may not be associated with greater incomplete revascularization) on DES-PCI outcomes is unclear. In the present study, complex coronary percutaneous revascularization in women was associated with higher unadjusted and adjusted risk of MACE, MI, TLR, and mortality. The association of procedural complexity with adverse outcomes is multifactorial. First, CPCI may imply the presence of complex CAD reflecting greater coronary and extra-coronary atherosclerotic burden and, therefore, greater atherothrombotic risk. Second, women undergoing CPCI are older and are more commonly affected by cardiovascular comorbidities, thus reflecting a high-risk population. Third, percutaneous revascularization in the presence of complex CAD may be associated with a greater likelihood of incomplete revascularization and residual CAD, which is well-known to affect ischemic and mortality outcomes in patients with multivessel CAD (20–23). The present findings refine the current knowledge on the prognosis of women undergoing complex percutaneous revascularization procedures.
New-generation DES in women undergoing CPCI
By improving drug release kinetics, polymer biocompatibility, and endothelialization patterns, new-generation DES significantly overcame the limitations observed with early-generation DES (24). However, the benefits demonstrated with new-generation DES are preserved in high-risk coronary anatomies and complex percutaneous revascularization procedures is to date unclear. In the present study, use of new-generation DES was associated with significant relative and absolute benefits in safety and efficacy metrics including ST, TLR, MACE, and even all-cause mortality. Irrespective of the time after the procedure, procedural complexity did not adversely affect the stent-related thrombotic benefits of new-generation DES; with comparable early, late or very-late risk of ST between CPCI and non-CPCI performed with new-generation platforms. Conversely, CPCI performed with first-generation DES was consistently associated with significantly higher risk of ST through 3 years of follow-up. These findings suggest that procedural complexity does not influence the thrombotic safety profile of new-generation DES; an effect that appears to be durable over time. Therefore, in a contemporary practice with new-generation platforms, women with advanced CAD undergoing complex percutaneous revascularization may not need prolonged (beyond 1 year) dual antiplatelet therapy with the rationale of preventing stent-related thrombotic complications; instead, more prolonged and intensified platelet inhibition would expose such patients to an unnecessary bleeding risk (25,26). As most of the stent-related thrombotic events occurred in the early phases, we cannot exclude that a customized approach to platelet inhibition with more potent agents administered early after PCI, followed by a switch to less potent agent or to a single antiplatelet agent, would provide improved net clinical benefit. However, irrespective of device generation, rates of MACE (which include stent- and nonstent-related coronary ischemic events) remain high after complex revascularization, suggesting that longer regimens of platelet inhibition alongside aggressive cardiovascular risk factor medical management might be beneficial in presence of a low hemorrhagic risk. In this setting (CPCI), prolonged dual antiplatelet therapy should be applied with the rationale of preventing non-DES-related coronary ischemic events associated with atherosclerotic disease progression outside the stented vascular segment; thus providing a broader atherothrombotic protection. Whether duration and potency of platelet inhibition should be tailored according to clinical and procedural complexity must be addressed in specific, prospective, randomized studies.
Use of new-generation DES was associated with a significant benefit in TLR in the CPCI subgroup. Even if the interaction test for TLR was not significant according to PCI complexity and DES generation, the magnitude of the HRs suggests an accentuation of the efficacy of new-generation devices in case of complex revascularization. Although previous RCTs and meta-analyses failed to demonstrate superiority in TLR of the second-generation everolimus- and sirolimus-eluting stents, this could have been related to smaller sample sizes and the inclusion of a large proportion of patients with simple coronary lesions or anatomies that could have attenuated the comparative effectiveness of the 2 DES platforms (27–29). Even if hypothesis-generating, the present finding provides a signal for an accentuated efficacy of new-generation devices in more challenging percutaneous revascularization procedures.
The present findings have to be viewed in light of the recently published studies comparing new-generation DES with coronary artery bypass graft surgery in patients with multivessel CAD, in which surgery was associated with reduced risk of MI and need for revascularization alongside an increased risk of early stroke (30,31). Although new-generation DES seem to narrow the disparities versus surgery in terms of effectiveness, they still do not totally fill the gap. The decision-making process for revascularization of advanced CAD is complex and must take into account the early hazard of surgery and the late complications associated with PCI. However, knowing that new-generation DES provide consistent benefits even in challenging coronary anatomies is reassuring and may support the use of PCI in this clinical setting in women with advanced CAD for whom coronary revascularization with surgery is not an option.
Although our findings rely on individual patient-level, high-quality data from prospective, randomized trials with data monitoring and event adjudication by clinical event committees, several limitations have to be disclosed. First, procedural complexity was defined according to the available variables in the pooled dataset. Although these include most of the high-level complexity scenarios encountered in clinical practice, some important variables, such as target vessel, vessel size, Medina class, or use of atherectomy, among others, were not available and were therefore not included in the present definition. Second, important variables that are known to be associated with adverse outcomes, such as duration and intensity of dual antiplatelet therapy and metrics of coronary artery disease complexity (SYNTAX score) and incomplete revascularization (residual SYNTAX score), were not available and were therefore not included. Third, some trials included in the analysis were performed more than a decade ago, during which time clinical practice and device technology have changed. To attenuate the trial-specific effect on outcomes, we included “trial” as a random effect in our adjusted analysis. Fourth, patient population across trials was heterogeneous; early trials enrolled lower risk patients with stable presentations and simple coronary artery lesions; conversely, recent trials included patients with higher clinical and anatomical complexity. Fifth, the lack of inclusion of male subjects in the pooled database precludes sex-specific analysis. Sixth, the results of this study have to be considered hypothesis-generating as it is a post hoc analysis from RCTs that were not designed to specifically assess DES outcomes in women undergoing CPCI.
Women undergoing CPCI are at higher risk of MACE and mortality at 3 years compared with those undergoing non-CPCI. Irrespective of procedural complexity, use of new-generation DES is associated with significantly improved safety and efficacy compared with early-generation DES, with a stent-related antithrombotic benefit that was more apparent in the very-late period (>1 year). The results of the present study clarify the prognostic significance of procedural complexity in women with CAD undergoing complex percutaneous revascularization with DES and confirm the results of RCTs of DES in this high-risk subset of patients.
WHAT IS KNOWN? New-generation DES demonstrated to be associated with improved safety and efficacy compared with early-generation DES in RCTs that included mostly a male population. Women more frequently have narrower, more tortuous vessels and more comorbidity at the time of coronary revascularization compared with men.
WHAT IS NEW? Women undergoing CPCI are at higher risk of mortality, revascularization, and MI compared with those undergoing non-CPCI. Compared with early-generation DES, new-generation DES provide consistent benefits, in particular on very-late thrombotic safety, irrespective of procedural complexity.
WHAT IS NEXT? Procedural complexity is a marker of risk in women. Optimal adjuvant pharmacotherapies targeting key molecular players in atherothrombosis and atherosclerosis progression might be useful in improving mid- to long-term outcomes following complex percutaneous revascularization procedures.
For supplemental tables, please see the online version of this article.
The Gender Data Forum was sponsored by the Women in Innovation Initiative of the Society of Cardiovascular Angiography and Interventions. Dr. Dangas' spouse has relationships with AstraZeneca, Bayer, CSL Behring, Jannsen Pharmaceuticals Inc., Merck & Co. Inc., Osprey Medical Inc., Regado Biosciences Inc., The Medicines Company, Watermark Consulting, Abbott Laboratories, Boston Scientific Corp., Covidien, sanofi-aventis, Elixir Medical Corp., and Claret Medical Inc. Dr. Stefanini has received speaker/consultant fees from Abbott Vascular, AstraZeneca, BBraun, Biotronik, and The Medicines Company. Dr. Steg has received a research grant (to INSERM U1148) from Sanofi and Servier; speaking or consulting fees from Amarin, AstraZeneca, Bayer, Boehringer-Ingelheim, Bristol-Myers Squibb, CSL-Behring, Daiichi-Sankyo, GlaxoSmithKline, Janssen, Lilly, Novartis, Pfizer, Regeneron, Roche, Sanofi, Servier, and The Medicines Company; and is a stockholder for Aterovax. Dr. Windecker has received research grants to his institution from Abbott Vascular, Biotronik, Boston Scientific, Medtronic, Edwards, and St. Jude Medical. Dr. Wijns has received institutional research grants from St. Jude Medical, Abbott Vascular, MiCell, Stentys and Boston Scientific; and is a non-executive board member and shareholder of Genae and Cardio3BioSciences. Dr. Smits has received institutional research grants form Abbott Vascular, Terumo, and St. Jude Medical. Dr. Kandzari has received research/grant support from Abbott Vascular, Biotronik, Boston Scientific, Medtronic CardioVascular, and Medinol; and consulting honoraria from Boston Scientific and Medtronic CardioVascular. Dr. von Birgelen is the PI on several randomized stent trials; has received lecture fees from AstraZeneca and MSD; is a consultant (advisory board member) to Abbott Vascular, Boston Scientific, and Medtronic; and his institution has received research grants from Abbott Vascular, AstraZeneca, Biotronik, Boston Scientific, and Medtronic to fund investigator-initiated, multi-center, randomized controlled trials and large registries. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.
- Abbreviations and Acronyms
- coronary artery disease
- complex percutaneous coronary intervention
- drug-eluting stent(s)
- myocardial infarction
- percutaneous coronary intervention
- randomized controlled trial
- stent thrombosis
- target lesion revascularization
- Received September 23, 2015.
- Revision received December 3, 2015.
- Accepted December 7, 2015.
- American College of Cardiology Foundation
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