Author + information
- Received May 11, 2015
- Revision received August 5, 2015
- Accepted September 10, 2015
- Published online January 11, 2016.
- Usman Baber, MD, MSc∗,
- Gennaro Giustino, MD∗,
- Samantha Sartori, PhD∗,
- Melissa Aquino, MSc∗,
- Giulio G. Stefanini, MD†,
- P. Gabriel Steg, MD‡,
- Stephan Windecker, MD, PhD§,
- Martin B. Leon, MD‖,
- William Wijns, MD, PhD¶,
- Patrick W. Serruys, MD, PhD#,
- Marco Valgimigli, MD, PhD∗∗,
- Gregg W. Stone, MD‖,
- George D. Dangas, MD, PhD∗,
- Marie-Claude Morice, MD††,
- Edoardo Camenzind, MD‡‡,
- Giora Weisz, MD#,
- Pieter C. Smits, MD, PhD§§,
- David Kandzari, MD‖‖,
- Clemens Von Birgelen, MD¶¶,
- Ioannis Mastoris, MD∗,
- Soren Galatius, MD##,
- Raban V. Jeger, MD∗∗∗,
- Takeshi Kimura, MD†††,
- Ghada W. Mikhail, MD‡‡‡,
- Dipti Itchhaporia, MD§§§,
- Laxmi Mehta, MD‖‖‖,
- Rebecca Ortega, MD¶¶¶,
- Hyo-Soo Kim, MD###,
- Adnan Kastrati, MD∗∗∗∗,
- Alaide Chieffo, MD†††† and
- Roxana Mehran, MD∗∗ ()
- ∗The Zena and Michael A. Wiener Cardiovascular Institute, Icahn School of Medicine at Mount Sinai, New York City, New York
- †Division of Clinical and Interventional Cardiology, Humanitas Research Hospital, Rozzano, Milan, Italy
- ‡Département Hospitalo Universitaire Fibrose, Inflammation et REmodelage, Assistance Publique-Hôpitaux de Paris, Université Paris Diderot, INSERM U698, Paris, France
- §Department of Cardiology, Bern University Hospital, Bern, Switzerland
- ‖Division of Cardiology, Columbia University Medical Center, New York City, New York
- ¶Cardiovascular Center Aalst, Onze-Lieve-Vrouwziekenhuis Ziekenhuis, Aalst, Belgium
- #Thoraxcenter, Erasmus MC, Rotterdam, the Netherlands
- ∗∗Department of Cardiology, University of Ferrara, Ferrara, Italy
- ††Department of Cardiology and Cardiovascular Surgery, Institut Cardiovasculaire Paris Sud, France
- ‡‡Institut Lorrain du Coeur et des Vaisseaux (ILCV) University Hospital Nancy—Brabois Vandoeuvre-lès-Nancy France
- §§Department of Cardiology, Maasstad Hospital, Rotterdam, the Netherlands
- ‖‖Piedmont Heart Institute, Atlanta, Georgia
- ¶¶Thoraxcentrum Twente, Enschede, the Netherlands
- ##Department of Cardiology, Bispebjerg University Hospital, Copenhagen, Denmark
- ∗∗∗Department of Cardiology, University Hospital Basel, Basel, Switzerland
- †††Department of Cardiology, Kyoto University Graduate School of Medicine, Kyoto, Japan
- ‡‡‡Department of Cardiology, Imperial College Healthcare NHS Trust, London, United Kingdom
- §§§Department of Cardiology, Hoag Memorial Hospital Presbyterian, Newport Beach, California
- ‖‖‖Department of Cardiology, Ohio State University Medical Center, Columbus, Ohio
- ¶¶¶Society of Cardiovascular Angiography and Interventions, Washington, DC
- ###Department of Cardiology, Seoul National University Main Hospital, Seoul, South Korea
- ∗∗∗∗Herzzentrum, Munich, Germany
- ††††Interventional Cardiology Unit, 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 This study sought to evaluate: 1) the effect of impaired renal function on long-term clinical outcomes in women undergoing percutaneous coronary intervention (PCI) with drug-eluting stent (DES); and 2) the safety and efficacy of new-generation compared with early-generation DES in women with chronic kidney disease (CKD).
Background The prevalence and effect of CKD in women undergoing PCI with DES is unclear.
Methods We pooled patient-level data for women enrolled in 26 randomized trials. The study population was categorized by creatinine clearance (CrCl) <45 ml/min, 45 to 59 ml/min, and ≥60 ml/min. The primary endpoint was the 3-year rate of major adverse cardiovascular events (MACE). Participants for whom baseline creatinine was missing were excluded from the analysis.
Results Of 4,217 women included in the pooled cohort treated with DES and for whom serum creatinine was available, 603 (14%) had a CrCl <45 ml/min, 811 (19%) had a CrCl 45 to 59 ml/min, and 2,803 (66%) had a CrCl ≥60 ml/min. A significant stepwise gradient in risk for MACE was observed with worsening renal function (26.6% vs. 15.8% vs. 12.9%; p < 0.01). Following multivariable adjustment, CrCl <45 ml/min was independently associated with a higher risk of MACE (adjusted hazard ratio: 1.56; 95% confidence interval: 1.23 to 1.98) and all-cause mortality (adjusted hazard ratio: 2.67; 95% confidence interval: 1.85 to 3.85). Compared with older-generation DES, the use of newer-generation DES was associated with a reduction in the risk of cardiac death, myocardial infarction, or stent thrombosis in women with CKD. The effect of new-generation DES on outcomes was uniform, between women with or without CKD, without evidence of interaction.
Conclusions Among women undergoing PCI with DES, CKD is a common comorbidity associated with a strong and independent risk for MACE that is durable over 3 years. The benefits of newer-generation DES are uniform in women with or without CKD.
Among patients with coronary artery disease (CAD) undergoing percutaneous coronary intervention (PCI), the presence of even mild chronic kidney disease (CKD) is associated with a strong and independent risk for adverse cardiovascular events (1–4). Moreover, several studies suggest that the safety and efficacy of drug-eluting stent (DES) implantation may be attenuated in the setting of renal dysfunction (5,6). Possible mechanistic linkages between CKD and cardiovascular risk after PCI include accelerated atherosclerosis within and outside of the stented vascular segment and a pro-inflammatory milieu (7). Moreover, enhanced blood thrombogenicity related to renal dysfunction increases risk for myocardial infarction (MI) and stent thrombosis (ST) in patients with CKD (7–9). Impaired renal function is also a common comorbidity among women undergoing PCI and may be a contributor to post-PCI risk in female patients (4,10,11). However, data on clinical outcomes associated with DES implantation in women with CKD are scarce as a result of their restricted inclusion in randomized controlled trials (RCTs).
In 2011, the Food and Drug Administration issued guidance for assessing sex disparities in RCTs evaluating medical devices (12). In response, the Society for Cardiovascular Angiography and Interventions’ Women in Innovation Initiative convened the Gender Data Forum to discuss the outcomes of DES in women, leading to the performance of an individual patient-level data pooled analysis from available randomized trials of DES. The safety and efficacy of DES in women have been previously reported (13). Accordingly, we sought to evaluate, by pooling patient-level data from RCTs, the prognostic effect of various degrees of impaired renal function in women undergoing PCI with DES and the safety and efficacy profile of new-generation compared with early-generation DES in women with CKD.
The rationale of the present patient-level pooled database, list of trials, analytic strategies, and pre-specified endpoints have been previously reported (13). Briefly, female participants from 26 RCTs were pooled: RAVEL (The Initial Double-Blind Drug-Eluting Stent vs Bare-Metal Stent Study) (14), SIRIUS (Study of Sirolimus-Coated BX VELOCITY Balloon-Expandable Stent in Treatment of de Novo Native Coronary Artery Lesions) (15), E-SIRIUS (The Study of the BX VELOCITY Stent In Patients With De Novo Coronary Artery Lesions) (16), C-SIRIUS (The Study of the BX Velocity Stent in the Treatment of De Novo Artery Lesions) (17), TAXUS-I (Randomized, Double-Blind Trial on a Slow-Release Paclitaxel-Eluting Stent for De Novo Coronary Lesions) (18), TAXUS-II SR (A Randomized Study to Assess the Effectiveness of Slow- and Moderate-Release Polymer-Based Paclitaxel-Eluting Stents for De Novo Coronary Artery Lesions) (19), TAXUS-IV (Treatment of De Novo Coronary Disease Using a Single Paclitaxel-Eluting Stent) (20), TAXUS-V (A Randomized, Double-blind Trial to Assess TAXUS Paclitaxel-Eluting Coronary Stents, SR Formulation, in the Treatment of De Novo Coronary Lesions) (21), SIRTAX (Sirolimus-Eluting Versus Paclitaxel-Eluting Stents for Coronary Revascularization) (22), ENDEAVOR II (Randomized Controlled Trial to Evaluate the Safety and Efficacy of the Medtronic AVE ABT-578 Eluting Driver Coronary Stent in De Novo Native Coronary Artery Lesions) (23), ENDEAVOR III (A Randomized Controlled Trial of the Medtronic Endeavor Drug [ABT-578] Eluting Coronary Stent System Versus the Cypher Sirolimus-Eluting Coronary Stent System in De Novo Native Coronary Artery Lesions) (24), ENDEAVOR-IV (Randomized Comparison of Zotarolimus-Eluting and Paclitaxel-Eluting Stents in Patients with Coronary Artery Disease) (25), SPIRIT II (A Clinical Evaluation of the XIENCE V Everolimus Eluting Coronary Stent System in the Treatment of Patients With de Novo Native Coronary Artery Lesions) (26), SPIRIT III (A Clinical Evaluation of the Investigational Device XIENCE V Everolimus Eluting Coronary Stent System in the Treatment of Subjects With de Novo Native Coronary Artery Lesions) (27), SPIRIT IV (Clinical Evaluation of the XIENCE V Everolimus Eluting Coronary Stent System in the Treatment of Subjects With de Novo Native Coronary Artery Lesions) (28), BASKET-PROVE (Evaluation of Late Clinical Events After Drug-eluting Versus Bare-metal Stents in Patients at Risk: BAsel Stent Kosten Effektivitäts Trial - PROspective Validation Examination Part II) (29), COMPARE I (A Randomized Controlled Trial of Everolimus-eluting Stents and Paclitaxel-eluting Stents for Coronary Revascularization in Daily Practice) (30), COMPARE II (Comparison of the Everolimus Eluting With the Biolimus A9 Eluting Stent) (31), EXCELLENT (The Efficacy of Xience/Promus Versus Cypher to Reduce Late Loss After Stenting) (11), RESET (REal Safety and Efficacy of 3-month dual antiplatelet Therapy following Endeavor zotarolimus-eluting stent implantation) (32), RESOLUTE AC (Randomized, Two-Arm, Non-inferiority Study Comparing Endeavor-Resolute Stent With Abbot Xience-V Stent) (33), TWENTE (The Real-World Endeavor Resolute Versus XIENCE V Drug-Eluting Stent Study in Twente) (34), LEADERS (A Randomized Comparison of a Biolimus-Eluting Stent With a Sirolimus-Eluting Stent for Percutaneous Coronary Intervention) (35), ISAR TEST 4 (Prospective, Randomized Trial of 3-limus Agent-eluting Stents With Different Polymer Coatings) (36), PRODIGY (PROlonging Dual Antiplatelet Treatment In Patients With Coronary Artery Disease After Graded Stent-induced Intimal Hyperplasia studY) (37), and PROTECT (Patient Related OuTcomes With Endeavor Versus Cypher Stenting Trial) (38). Characteristics of the RCTs included in the present study are summarized in Online Table 1. All of the included randomized controlled trials were performed between 2000 and 2013.
According to baseline creatinine clearance (CrCl), the study population was stratified by: 1) CrCl <45 ml/min, 2) CrCl between 45 and 59 ml/min, and 3) CrCl ≥60 ml/min (Figure 1). Women receiving bare-metal stents were excluded from the present analysis. Participants whose baseline creatinine was not available were also excluded from the analysis.
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-eluting stents, zotarolimus-eluting stents with durable polymer, and biolimus- and sirolimus-eluting stents with biodegradable polymer).
We evaluated the effect of impaired renal function on 3-year risk of major adverse cardiac events (MACE) defined as the composite of all-cause death, MI, target lesion revascularization (TLR), or ST. Subsequently, we evaluated the effect of new-generation DES (versus early-generation DES) on the risk of device-oriented safety endpoints comprising cardiac death, MI, or ST. The clinical endpoint definitions used across trials are shown in Online Table 2.
No funding source was available for the gathering of these data, statistical analyses, or drafting of this report. The collaborative nature of the present investigation initiative has been reported previously (14). All of the contacted principal investigators and device manufacturers shared individual patient data for female patients enrolled in randomized controlled trials evaluating the safety and efficacy of different types of DES.
All patient-level data were aggregated and combined as 1 dataset using pre-specified extraction sheet. Baseline clinical, demographic, and procedural characteristics of CKD groups were compared using linear regression for continuous variables and chi-square tests for categorical variables. Cumulative event rates were calculated with the Kaplan-Meier method and compared between groups using 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. The median follow-up time was 3 years in patients with CrCl ≥60 ml/min and between 45 and 59 ml/min, and was 2 years in those with CrCl <45 ml/min. The independent associations between CKD severity and 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 (39,40). 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 is interpreted as a metric of heterogeneity in baseline risk between trials. In the analysis evaluating the effect of renal function on outcomes, CrCl >60 ml/min served as the referent category. For the DES-level analysis, older-generation DES served as the referent category. As median follow-up time differed significantly across stent generations (2 and 3 years among those receiving new- and older-generation DES, respectively), comparative analyses between DES groups were censored at 2 years. Stent group, age, and baseline variables showing significant differences between groups were included as covariates in the multivariable model (body mass index, diabetes, previous myocardial infarction, family history of CAD, previous percutaneous intervention for multivessel disease, smoking, presentation with an acute coronary syndrome, number of stents per patient, and type B2 or C lesions). For the DES-level analysis, the consistency of the effect of new-generation DES in patients with or without CKD was evaluated with a formal interaction test. We judged p values <0.05 to be significant, and all analyses were done with SAS version 9.2 software (SAS Institute, Cary, North Carolina).
Of 10,620 women included in the pooled dataset and who received a DES, baseline creatinine level was available for 4,217 (39.7%). Of them, 1,414 had CKD (33.5%). Among those with CKD, 603 (14.3%) had severe renal impairment (CrCl <45 ml/min) and 811 (19.2%) had moderate renal impairment (CrCl 45 to 59 ml/min).
Clinical characteristics according to baseline renal function are reported in Table 1. Women with CrCl <45 ml/min were older, had lower body mass index, and had greater prevalence of diabetes mellitus, arterial hypertension, previous MI, and previous percutaneous or surgical coronary revascularization. Conversely, they had lower prevalence of family history of CAD, active smoking, and hypercholesterolemia. Angiographic and procedural data are reported in Table 1. Women with CrCl <45 ml/min had a higher prevalence of multivessel CAD, moderate or severe calcifications, and type B2/C lesions and had longer total stent length.
Effect of renal function on 3-year clinical outcomes
A significant stepwise increase in 3-year rates of MACE (Figure 2A, Online Figure 1) (12.9% vs. 15.8% vs. 26.6%; p < 0.01), all-cause mortality (Figure 2B) (3.1% vs. 6.4% vs. 16.1%; p < 0.01), cardiac mortality (3.1% vs. 6.4% vs. 16.1%; p < 0.01), MI (5.2% vs. 6.3% vs. 10.2%; p < 0.01), and the composite of death, MI, or stent thrombosis (8.0% vs. 11.1% vs. 22.4%; p < 0.01) was observed in the transition from normal (CrCl ≥60 ml/min) to severely impaired renal function (CrCl <45 ml/min). Conversely, there were no differences in the rate of TLR at 3 years among groups (6.4% vs. 6.1% vs. 6.8%; p = 0.77).
Following adjustment for baseline confounders, severe impairment of renal function (CrCl <45 ml/min) was independently associated with an increased risk of MACE (Table 2) (adjusted hazard ratio [adjHR]: 1.56; 95% confidence interval [CI]: 1.23 to 1.98; trend p < 0.01), all-cause mortality (adjHR: 2.67; 95% CI: 1.85 to 3.85; trend p < 0.01), cardiac mortality (adjHR: 2.75; 95% CI: 1.65 to 4.61; trend p < 0.01), MI (HR: 1.33; 95% CI: 0.90 to 1.97; trend p < 0.01), and the composite of death, MI, or stent thrombosis (adjHR: 1.85; 95% CI: 1.40 to 2.44; trend p < 0.01) compared with normal renal function (CrCl ≥60 ml/min) or moderate renal impairment (CrCl 45 to 59 ml/min). Moreover, a trend toward a higher risk of ST was observed in patients with severely impaired renal function (adjHR: 1.54; 95% CI: 0.70 to 3.39; trend p = 0.05). Conversely, severe renal impairment was not associated with an increased risk of TLR. Finally, moderate renal dysfunction (CrCl 45 to 59 ml/min) was not independently associated with a higher risk of adverse events compared with normal renal function.
Early- versus new-generation DES in women with CKD
In women with CKD, at unadjusted analysis, new-generation DES were associated with lower 2-year rates of the composite of cardiac death, MI, or stent thrombosis (Figure 3A) (9.2% vs. 11.1%; p = 0.002) and cardiac death (Figure 3B) (5.6% vs. 4.2%; p < 0.0001). Following multivariable adjustment for baseline confounders (Table 3), use of new-generation DES in women with CKD was associated with a reductions in cardiac death, MI, or ST (adjHR: 0.70; 95% CI: 0.49 to 1.00), death or MI (adjHR: 0.72; 95% CI: 0.53 to 1.00), and cardiac death (adjHR: 0.58; 95% CI: 0.35 to 0.97). The magnitude and direction of the effect of new-generation DES use was uniform between patients with or without CKD, with no evidence of interaction. The effect of new-generation DES on outcomes was consistent using a CrCl threshold of <45 ml/min (Online Table 3).
To the best of our knowledge, the present report is the largest to date to examine the effect of CKD and different DES platforms on long-term risk after PCI in female randomized trial participants. Our results demonstrate that: 1) CKD is a common comorbidity among women undergoing PCI with DES and is associated with a strong and durable risk for MACE and mortality; 2) the effect of renal dysfunction on adverse events is graded, particularly among those with CrCl <45 ml/min; and 3) compared with early-generation DES, use of newer-generation DES is associated with improved safety and efficacy in women with CKD.
Effect of renal function on adverse events in women
Consistent with previous reports evaluating the effect of CKD in cardiovascular disease, impaired renal function was associated with a higher risk for MACE and death compared with preserved renal function (7,8). We observed an inflection point for excess risk at levels of CrCl <45 ml/min, similar to a threshold previously reported in a large population-based sample of U.S. adults (7). Despite these well-documented associations, analogous data examining long-term outcomes in women with CKD across the spectrum of clinical CAD presentations remain limited. Among ST-segment elevation MI patients, for example, a post-hoc analysis of the HORIZONS-AMI (Harmonizing Outcomes With Revascularization and Stents in Acute Myocardial Infarction) trial showed substantial and excess thrombotic risk associated with CKD in both male and female patients. Renal impairment was not linked with higher rates of TLR in that report, as is consistent with our results. Consequently, our findings, in concert with earlier observations, highlight the prognostic relevance of renal dysfunction as a strong and robust marker of excess long-term risk in women undergoing PCI.
Renal-attributable risk is at least partially due to the higher prevalence of comorbidities that increase in the transition from normal to severely impaired renal function (CrCl <45 ml/min). Concordant with this clinical phenotype, we also showed a greater burden and complexity of CAD among women with CrCl <45 ml/min. Nevertheless, the association between moderate to severe renal dysfunction and increased MACE risk persisted after adjusting for baseline imbalances between CKD groups, suggesting that alternative and independent mechanisms may be contributory in such patients. Indeed, common risk factors for both CKD and atherosclerosis, including advanced age, arterial hypertension, dyslipidemia and diabetes mellitus, suggest a shared pathophysiological substrate for both conditions, yet do not fully account for the observed morbidity in female patients with moderate to severe CKD. Excess risk may also be attributable to a systemic inflammatory state, oxidative stress, and significant endothelial dysfunction, factors that may act in a synergistic manner to enhance thrombosis (7,10).
Of note, baseline creatinine levels were available in less than one-half of our entire pooled patient population. Given the importance of CKD as a risk factor for subsequent MACE and mortality, this finding emphasizes the importance to measure baseline creatinine levels in patients undergoing PCI for optimal risk stratification and implementation of strategies to avoid contrast-induced nephropathy.
New-generation DES in women with CKD
Compared with early-generation DES, the improved safety and efficacy of new-generation DES has been demonstrated in a multitude of RCTs and meta-analyses (41). In the present study, we shed light on the relative safety and efficacy of new-generation DES in women with CKD. Although previous studies suggested an attenuation of benefit of newer-generation DES in the setting of CKD (6,42), we observed nondifferential reduction in risks for cardiac death, MI, or ST irrespective of CKD status. Potential mechanisms by which CKD might increase the risk of DES failure include enhanced propensity for thrombosis, increased systemic inflammation, disturbances in glucose homeostasis that might affect the patterns of endothelialization and the burden of neointimal hyperplastic response, and a milieu of accelerated atherosclerosis with subsequent development of neoatherosclerosis within the implanted DES platform. However, newer-generation DES, by optimization of biocompatibility, drug-release kinetics, vascular healing, and endothelial coverage, overcome limitations of early-generation DES and provide consistent benefits irrespective of renal function (41).
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, some trials included in the analysis were performed more than 1 decade ago, since which time clinical practice and device technology have changed. To reduce the trial effect on outcomes, we included trial as a random effect in our adjusted analyses. Second, patient populations across trials were heterogeneous; early trials focused only on stable CAD with simple lesions, whereas more recent trials included more complex patient and lesion subsets. Third, the exclusion of male participants from this study precludes sex-specific analysis, limiting the external validity of our findings. Fourth, as a post-hoc analysis of randomized trials, our results are subject to residual or unmeasured confounding. Fifth, the relatively low numbers for each early- and new-generation DES type limits our ability to perform between-stent comparisons within each renal function category. Sixth, angiographic follow-up was not available in the pooled dataset, mitigating our ability to compare angiographic performances of new-generation DES in such a high-risk population. Seventh, serum creatinine was not available in all study participants (>10,000 women), rendering our point estimates and subgroup comparisons less precise. Finally, data on dual antiplatelet therapy adherence, potency, and duration were not available, limiting the findings of the DES generation-level analysis.
CKD is a common comorbidity among women with CAD undergoing percutaneous revascularization with DES. Impaired renal function is associated with a strong, dose-dependent effect on the long-term risk of MACE and mortality. Compared with early-generation DES, use of newer-generation DES is associated with consistent and uniform benefits in women with or without CKD.
WHAT IS KNOWN? Previous studies suggested that CKD attenuates the safety and efficacy of new-generation DES. The magnitude of this effect in women undergoing PCI is unknown.
WHAT IS NEW? Among women undergoing PCI with DES, CKD is a common comorbidity associated with a strong and independent risk of major adverse events and mortality. Compared with early-generation DES, new-generation devices are associated with consistent and uniform benefits in women with or without CKD.
WHAT IS NEXT? Evaluation of renal function in women undergoing PCI should be a standard of care for optimal risk stratification and implementation of contrast-induced nephropathy avoidance strategies.
The Gender Data Forum was sponsored by the Women in Innovation Initiative of the Society of Cardiovascular Angiography and Interventions. Dr. Stefanini has received speaker fees from Abbott Vascular, AstraZeneca, Biosensors, Biotronik, and The Medicines Company. Dr. Steg has received honorarium from Medtronic as a steering committee member in the PROTECT trial; has received research grants from Sanofi and Servier; has received funding from Amarin, AstraZeneca, Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, Daiichi-Sankyo-Lilly, GlaxoSmithKline, Medtronic, Merck, Novartis, Pfizer, Regeneron, Sanofi, Servier, and The Medicines Company; and is a stockholder in Aterovax. Dr. Windecker has received research contracts to the institution from Abbott, Biotronik, Boston Scientific, Biosensors, Cordis, Medtronic, and St. Jude; and has received speakers honoraria from AstraZeneca, Eli Lilly, Abbott, Biotronik, Biosensor, Boston Scientific, Medtronic, Edwards Lifesciences, and Bayer. Dr. Wijns has received institutional research grants from Boston, Medtronic, Abbott, Terumo, and Biosensors; is an investigator for sponsored trials by Boston, Medtronic, Abbott, Terumo, and Biosensors; is a nonexecutive board member and shareholder of Argonauts Partners, Cardio3BioSciences, and Genae; and fees or honoraria on his behalf from Boston, Medtronic, Abbott, Terumo, and Biosensors go to the Cardiovascular Center Aalst. Dr. Valgimigli has received honoraria for lectures or advisory board and research grants from Merck, Iroko, Eli Lilly, and Medtronic; honoraria for advisory board and lectures from The Medicines Company, Eli Lilly, Daiichi Sankyo, St. Jude, and Abbott Vascular; and honoraria for lectures from Cordis, Carbostent and Implantable Devices, and Terumo. Dr. Smits has received institutional research grants and speakers fees from Abbott Vascular, St. Jude, and Terumo.
Dr. Kandzari has received research or grant support from Medtronic, Abbott, and Boston Scientific; and has received consulting honoraria from Medtronic, Biotronik, and Boston Scientific. Dr. Von Birgelen is a consultant to and has received lecture fees or travel expenses from Abbott Vascular, AstraZeneca, Biotronik, Boston Scientific, Medtronic, and Merck Sharp and Dohme; and his research department Thoraxcentrum Twente has received educational or research grants from Abbott Vascular, AstraZeneca, Biotronik, Boston Scientific, and Medtronic.
Dr. Galatius has received grant support from St. Jude, Abbott, Terumo, and Biotronik; and has received advisory board honorarium from Eli Lilly and Servier. Dr. Mikhail has received an interventional fellowship from Abbott Vascular; and has received speakers honoraria from AstraZeneca. Dr. Mehran has received institutional research grant support from The Medicines Company, AstraZeneca, Bristol-Myers Squibb, Sanofi, Lilly, and Daiichi Sankyo; has received consulting fees from Abbott Vascular, AstraZeneca, Bayer, Boston Scientific, CSL Behring, Covidien, Janssen Pharmaceuticals, Maya Medical, Merck, Osprey Medical Inc., Regado Biosciences, Watermark Research Partners, and Sanofi; and serves on the scientific advisory board of Abbott Laboratories, Boston Scientific Corporation, Covidien, Janssen Pharmaceuticals, The Medicines Company, and Sanofi. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose. The first 2 authors contributed equally to this work.
- Abbreviations and Acronyms
- coronary artery disease
- chronic kidney disease
- creatinine clearance
- drug-eluting stent(s)
- myocardial infarction
- percutaneous coronary intervention
- randomized controlled trial
- stent thrombosis
- target lesion revascularization
- Received May 11, 2015.
- Revision received August 5, 2015.
- Accepted September 10, 2015.
- American College of Cardiology Foundation
- Saltzman A.J.,
- Stone G.W.,
- Claessen B.E.,
- et al.
- Baber U.,
- Mehran R.
- Di Angelantonio E.,
- Chowdhury R.,
- Sarwar N.,
- Aspelund T.,
- Danesh J.,
- Gudnason V.
- Sederholm Lawesson S.,
- Todt T.,
- Alfredsson J.,
- Janzon M.,
- Stenestrand U.,
- Swahn E.
- Latif F.,
- Kleiman N.S.,
- Cohen D.J.,
- et al.
- Park K.W.,
- Chae I.H.,
- Lim D.S.,
- et al.
- ↵US Food and Drug Administration. Draft guidance for industry and Food and Drug Administration staff: evaluation of sex diff erences in medical device clinical studies. Available at: http://www.fda.gov/MedicalDevices/DeviceRegulationandGuidance/GuidanceDocuments/ucm283453.htm. Accessed June 18, 2013.
- Schampaert E.,
- Cohen E.A.,
- Schluter M.,
- et al.
- Grube E.,
- Silber S.,
- Hauptmann K.E.,
- et al.
- Colombo A.,
- Drzewiecki J.,
- Banning A.,
- et al.
- Fajadet J.,
- Wijns W.,
- Laarman G.J.,
- et al.
- Kandzari D.E.,
- Leon M.B.,
- Popma J.J.,
- et al.
- Leon M.B.,
- Mauri L.,
- Popma J.J.,
- et al.
- Kimura T.,
- Morimoto T.,
- Natsuaki M.,
- et al.
- von Birgelen C.,
- Basalus M.W.,
- Tandjung K.,
- et al.
- Byrne R.A.,
- Kastrati A.,
- Kufner S.,
- et al.
- Valgimigli M.,
- Campo G.,
- Monti M.,
- et al.
- Tsai T.T.,
- Messenger J.C.,
- Brennan J.M.,
- et al.