Author + information
- Received April 5, 2016
- Revision received May 17, 2016
- Accepted June 16, 2016
- Published online September 26, 2016.
- Gennaro Giustino, MDa,
- Ioannis Mastoris, MDa,
- Usman Baber, MD, MSca,
- Samantha Sartori, PhDa,
- Gregg W. Stone, MDb,
- Martin B. Leon, MDb,
- Patrick W. Serruys, MD, PhDc,
- Adnan Kastrati, MDd,
- Stephan Windecker, MD, PhDe,
- Marco Valgimigli, MD, PhDe,
- George D. Dangas, MD, PhDa,
- Clemens Von Birgelen, MDf,
- Pieter C. Smits, MDg,
- David Kandzari, MDh,
- Soren Galatius, MDi,
- William Wijns, MDj,
- P. Gabriel Steg, MD, PhDk,
- Giulio G. Stefanini, MD, PhDl,
- Melissa Aquino, MSca,
- Marie-Claude Morice, MDm,
- Edoardo Camenzind, MDn,
- Giora Weisz, MDo,p,
- Raban V. Jeger, MDq,
- Takeshi Kimura, MDr,
- Ghada W. Mikhail, MDs,
- Dipti Itchhaporia, MDt,
- Laxmi Mehta, MDu,
- Rebecca Ortega, MDv,
- Hyo-Soo Kim, MDw,
- Alaide Chieffo, MDx and
- Roxana Mehran, MDa,∗ ()
- aInterventional Cardiovascular Research and Clinical Trials, The Zena and Michael A. Wiener Cardiovascular Institute, Icahn School of Medicine at Mount Sinai, New York, New York
- bDepartment of Cardiology, Columbia University Medical Center, New York, New York
- cDepartment of Cardiology, Erasmus MC, Rotterdam, the Netherlands
- dDepartment of Cardiology, Herzzentrum, Munich, Germany
- eDepartment of Cardiology, Bern University Hospital, Bern, Switzerland
- fDepartment of Cardiology, Thoraxcentrum Twente, Enschede, the Netherlands
- gDepartment of Cardiology, Maasstad Hospital, Rotterdam, the Netherlands
- hPiedmont Heart Institute, Atlanta, Georgia
- iDepartment of Cardiology, Bispebjerg University Hospital, Copenhagen, Denmark
- jCardiovascular Center Aalst, Onze-Lieve-Vrouwziekenhuis Ziekenhuis, Aalst, Belgium
- kDépartement Hospitalo Universitaire Fibrose, Inflammation et Remodelage, Assistance Publique-Hôpitaux de Paris, Université Paris Diderot, INSERM U114, Paris, France
- lDivision of Clinical and Interventional Cardiology, Humanitas Research Hospital, Rozzano, Milan, Italy
- mDepartment of Cardiology and Cardiovascular Surgery, Institut Cardiovasculaire Paris Sud, Paris, 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
- pColumbia University Medical Center, New York, New York
- qDepartment of Cardiology, University Hospital Basel, Basel, Switzerland
- rDepartment of Cardiology, Kyoto University Graduate School of Medicine, Kyoto, Japan
- sDepartment of Cardiology, Imperial College Healthcare NHS Trust, London, United Kingdom
- tDepartment of Cardiology, Hoag Memorial Hospital Presbyterian, Newport Beach, California
- uDepartment of Cardiology, The Ohio State University Medical Center, Columbus, Ohio
- vDuke Clinical Research Institute, Durham, North Carolina
- wDepartment of Cardiology, Seoul National University Main Hospital, Seoul, Korea
- xCardiothoracic 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 aim of this study was to investigate the clinical correlates and prognostic impact of coronary artery calcification (CAC) in women undergoing percutaneous coronary intervention with drug-eluting stents (DES).
Background The clinical correlates and the prognostic significance of CAC in women undergoing percutaneous coronary intervention with DES remain unclear.
Methods Patient-level data from female participants in 26 randomized trials of DES were pooled. Study population was categorized according to the presence of moderate or severe versus mild or no target lesion CAC, assessed through coronary angiography. Co–primary endpoints of interest were the composite of death, myocardial infarction (MI), or target lesion revascularization and death, MI, or stent thrombosis at 3-year follow-up.
Results Among 11,557 women included in the pooled dataset, CAC status was available in 6,371 women. Of these, 1,622 (25.5%) had moderate or severe CAC. In fully adjusted models, independent correlates of CAC were age, hypertension, hypercholesterolemia, smoking, previous coronary artery bypass graft surgery, and worse left ventricular and renal function. At 3 years, women with CAC were at higher risk for death, MI, or target lesion revascularization (18.2% vs. 13.1%; adjusted hazard ratio: 1.56; 95% confidence interval: 1.33 to 1.84; p < 0.0001) and death, MI, or stent thrombosis (12.7% vs. 8.6%; adjusted hazard ratio: 1.48; 95% confidence interval: 1.21 to 1.80; p = 0.0001). The adverse effect of CAC on ischemic outcomes appeared to be consistent across clinical and angiographic subsets of women, including new-generation DES.
Conclusions Women undergoing PCI of calcified lesions tend to have worse clinical profile and remain at increased ischemic risk, irrespective of new-generation DES.
Coronary artery calcification (CAC) has been recognized has a marker of cardiovascular risk in the general population and in patients undergoing percutaneous coronary intervention (PCI) (1). CAC is associated with vascular stiffness, abnormal vasomotor activity, and stress-induced myocardial ischemia. Additionally, the extent of CAC tightly correlates with the extent of systemic atherosclerosis, plaque burden, and risk for future cardiovascular adverse events (1). CAC occurrence is both age and sex specific, with increased prevalence in older patients, particularly of male sex. In patients undergoing PCI, calcified lesions represent a challenging subset (1). The presence of CAC may impair stent delivery and optimal expansion and possibly damage the polymer and/or drug coating, predisposing to future stent failure with restenosis and thrombosis. Importantly, the deleterious effects of CAC on PCI outcomes have been demonstrated with both bare-metal stents and drug-eluting stents (DES) and across the entire clinical spectrum of coronary artery disease (CAD) (1–4).
Substantial sex-specific differences have been described in coronary artery anatomy, degree and patterns of atherosclerosis, and coronary plaque morphology (5). Despite more clinical comorbidities, women with symptomatic CAD tend to have a lower prevalence of multivessel disease, and lower extent of coronary atherosclerosis, calcifications, and features of high-risk plaques (5,6). Considering that women have been historically underrepresented in randomized clinical trials (RCTs) investigating the safety and efficacy of cardiovascular devices, and given the lower prevalence of significant CAC in women compared with men, the impact on outcomes of CAC in women undergoing PCI with DES remains unclear. In 2011, a U.S. Food and Drug Administration guidance document identified sex-specific disparities in RCTs investigating medical devices. In response to these observations, under the auspices of the Women in Innovation (WIN) initiative of the Society for Cardiovascular Angiography and Interventions, the present collaborative, women-specific, patient-level pooled dataset of RCTs of DES was created (7). In the present study, we sought to investigate the clinical correlates and impact of CAC in women undergoing PCI with early- and new-generation DES.
Study population and design
The methods and rationale of the present collaboration have been previously published (7–11). In response to the Food and Drug Administration guidance document for the assessment of sex differences in clinical studies of medical devices, the WIN initiative convened the Gender Data Forum to discuss the outcomes of DES implantation in women. This forum led to the investigation of the efficacy and safety of DES in women by pooling individual patient-level data from all available RCTs of DES. Patient-level data were pooled from 26 RCTs. The full list of the included RCTs, study characteristics, and endpoint definitions are reported in Online Tables 1 and 2. All studies included in our analysis complied with the provisions of the Declaration of Helsinki, and the Institutional Review Board at each center approved the study protocols.
For the present analysis, the following exclusion criteria were applied in the overall pooled dataset (Figure 1): 1) women randomized to bare-metal stent treatment; 2) trials with target lesion moderate or severe CAC as an exclusion criterion; and 3) women with missing information regarding target lesion CAC. In all included RCTs, CAC was assessed by means of qualitative and/or quantitative coronary angiography in a dedicated central angiographic core laboratory. Technicians performing quantitative coronary angiography were blinded to treatment allocation and outcomes for all patients within each trial. Qualitative analysis was performed with the modified American College of Cardiology and American Heart Association classification (12). Calcification was identified as readily apparent radio-opacities within the vascular wall at the site of the stenosis and was classified as none or mild, moderate (radio-opacities noted only during the cardiac cycle before contrast injection), or severe (radio-opacities noted without cardiac motion before contrast injection generally compromising both sides of the arterial lumen). On the basis of the calcification grade described in the aforementioned classification, our cohort was divided into none or mild versus moderate or severe target lesion CAC (Figure 1).
The primary objectives of the present study were: 1) to investigate the cross-sectional clinical correlates of CAC in women undergoing PCI with DES; 2) to evaluate the longitudinal prognostic impact of target lesion CAC; and 3) to assess the effect of target lesion CAC across high-risk clinical and angiographic subsets of women. The co–primary endpoints of interest were the 3-year risk for the composite of death, myocardial infarction (MI), or target lesion revascularization (TLR) and the composite of death, MI, or definite or probable stent thrombosis (ST). Secondary endpoints included the single components of the 2 co–primary endpoints and cardiac death. Study endpoint definitions used in the included RCTs are reported in Online Tables 1 and 2.
The DES used in the RCTs included in the present pooled analysis were sirolimus-eluting stents (Cypher, Cordis, Miami Lakes, Florida), paclitaxel-eluting stents (Taxus, Boston Scientific, Natick, Massachusetts), everolimus-eluting stents (XIENCE [Abbott Vascular, Santa Clara, California] and Promus [Boston Scientific]), zotarolimus-eluting stents (Endeavor [Medtronic, Minneapolis, Minnesota] and Resolute [Medtronic]), biolimus (umirolimus)–eluting stents with biodegradable polymer coating (Biomatrix [Biosensors, Newport Beach, California] and Nobori [Terumo, Tokyo, Japan]), and sirolimus-eluting stents with biodegradable polymer coating (Yukon, Translumina, Hechingen, Germany). DES 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).
Patient-level data were aggregated and combined as 1 dataset on a pre-specified extraction sheet. Baseline demographic, procedural, and clinical characteristics by CAC (none or mild vs. moderate or severe) were compared using the Student t test for continuous variables and the chi-square test for categorical variables. Cumulative event rates were estimated using the Kaplan-Meier method and compared using the log-rank test. Outcomes are provided at 3 years after index PCI. The temporal consistency of the effect of CAC on outcomes was assessed by performing Kaplan-Meier landmark analyses in the early and late periods (0 to 1 year) and very late period (1 to 3 years) for the main outcomes of interest. The independent association between baseline clinical variables and the presence of moderate or severe CAC was investigated with cross-sectional logistic regression analysis. For the purpose of this analysis, 2 models were performed: 1 excluding renal and left ventricular function and 1 taking into account renal and left ventricular function. The independent association between CAC and outcomes was evaluated with Cox proportional hazards. The covariates included in the Cox regression model were age, diabetes mellitus, acute coronary syndrome as clinical presentation, prior MI, prior PCI, prior coronary artery bypass graft surgery, smoking status, and type of DES implanted. The proportionality assumption was verified by means of the scaled Schoenfeld residual. Both the logistic regression and Cox regression models included a frailty term (γ) to assess random effects in the trials (to account for intertrial heterogeneity). 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. Multicollinearity was evaluated by means of visual inspection of the correlation matrix and by estimation of the variance inflation factor (with >10 used as a threshold to define significant multicollinearity). The effect of CAC on the 2 co–primary endpoints was investigated within the following subgroups of interest: age >65 years, diabetes mellitus, prior MI, chronic kidney disease (defined as creatinine clearance <60 ml/min), smoking status, CAD presentation, more than 2 DES implanted, more than 30 mm total stent length, bifurcation lesion as target vessel, and DES generation (early- and new-generation DES). The effect of CAC on the risk for device-oriented endpoints (TLR and definite or probable ST) was also evaluated according to DES generation. Effect consistency was estimated by means of formal interaction testing. We judged p values <0.05 as indicating statistical significance. All analyses were performed with Stata version 12.0 (StataCorp LP, College Station, Texas).
The study population flowchart is illustrated in Figure 1. Among 26 included RCTs, CAC of the target lesion was an exclusion criterion in 8 RCTs (2,720 women). Following exclusion of women randomized to bare-metal stents and those in whom CAC data were missing, 6,371 women remained analyzable. Of these, 1,622 (25.5%) had moderate or severe CAC. Women with moderate or severe CAC were significantly older, with a higher prevalence of hypertension, hypercholesterolemia, prior coronary artery bypass graft surgery, higher serum creatinine, and lower left ventricular ejection fraction (Table 1). Women with CAC more commonly had stable CAD presentation. Angiographically, women with moderate or severe CAC had higher prevalence of multivessel disease and a larger number of lesions treated, stents implanted, total stent length, and bifurcation lesion as target vessel.
Independent clinical correlates of CAC in women are illustrated in Table 2. In the partially adjusted model (without including renal and left ventricular function), the independent correlates associated with higher likelihood of CAC were age, body mass index, insulin-dependent diabetes, hypercholesterolemia, smoking, and previous coronary artery bypass graft surgery. Conversely, the clinical correlates associated with lower likelihood of CAC were unstable angina and ST-segment elevation MI as clinical presentation. In the fully adjusted model, both higher serum creatinine and lower left ventricular ejection fraction emerged as independent correlates of CAC.
Unadjusted and adjusted 3-year outcomes per CAC status are reported in Table 3. Women with moderate or severe CAC had higher crude and adjusted risk for both the co–primary endpoints of death, MI, or TLR (18.2% vs. 13.1%; adjusted hazard ratio [HR]: 1.56; 95% confidence interval [CI]: 1.33 to 1.84; p < 0.0001) (Figure 2A) and death, MI, or ST (12.7% vs. 8.6%; adjusted HR: 1.48; 95% CI: 1.21 to 1.80; p = 0.0001) (Figure 2B). Moderate or severe CAC was also associated with increased risk for death, cardiac death, spontaneous MI, and TLR (Figure 2C). Conversely, although moderate or severe CAC was associated with higher unadjusted risk for definite or probable ST (1.5% vs. 0.9%; univariate HR: 1.73; 95% CI: 1.05 to 2.86; p = 0.03) (Figure 2D), this was attenuated following multivariate adjustment (adjusted HR: 1.52; 95% CI: 0.89 to 2.59; p = 0.13).
Landmark analyses between 0 and 1 year and 1 and 3 years are illustrated in Figure 3. The presence of moderate or severe CAC was consistently associated with higher rates of death, MI, or TLR (Figure 3A) and death, MI, or ST (Figure 3B) in the early or late (0 to 1 year) and very late (1 to 3 years) periods. Regarding TLR, moderate or severe CAC was associated with higher rates in the first year, but there were no significant differences in the very late period (Figure 3C). Finally the rates of definite or probable ST were numerically increased in the moderate or severe CAC group during both the early or late and very late periods (Figure 3D).
The effect of moderate or severe CAC on the risk for the 2 co–primary endpoints across clinical and angiographic subgroups is illustrated in Figure 4. There was no significant heterogeneity in the risk for death, MI, or TLR (Figure 4A) and death, MI, or ST (Figure 4B) across the specified subgroups, including new-generation DES. Additionally, the effect of CAC on TLR and definite or probable ST was uniform between new-generation DES (for TLR, adjusted HR: 1.57; 95% CI: 1.14 to 2.16; for ST, adjusted HR: 1.78; 95% CI: 0.87 to 3.64) and early-generation DES (for TLR, adjusted HR: 1.19; 95% CI: 0.83 to 1.70; for ST, adjusted HR: 1.41; 95% CI: 0.65 to 3.07), without evidence of interaction (for TLR, pinteraction = 0.23; for ST, pinteraction = 0.49).
In the present analysis, we pooled patient-level data from 26 randomized trials of women undergoing PCI with DES, thus comprising a unique cohort of 6,371 female participants with available CAC status. The present study is to our knowledge the largest to date assessing the clinical correlates and impact of CAC on ischemic outcomes in a female population undergoing PCI with DES. The main results of our study can be summarized as follows (Figure 5): 1) the presence moderate or severe CAC was more commonly associated with other clinical and anatomic markers of cardiovascular risk; 2) women with moderate or severe CAC were at higher risk for death, MI, or TLR and death, MI, or ST at 3-year follow-up, an association that persisted following multivariate adjustment; 3) the effect of CAC on the 2 co–primary composite endpoints appeared to be consistent between 0 to 1 year and 1 to 3 years after the index procedure, whereas the effect on TLR appeared to be increased in the first year and to then attenuate in the very late period (after 1 year); and 4) the harmful effect of CAC on major adverse events was consistent across clinical and angiographic subgroups, including new-generation DES.
CAC is a marker of the extent of coronary atherosclerosis, and longitudinal evaluation of CAC burden allows the estimation of future atherothrombotic risk (1). The occurrence of CAC is both age and sex specific, with higher prevalence in older patients and men, and strongly correlates with the burden of both coronary and systemic atherosclerosis (1,13). A previous report showed that the prevalence of detectable CAC in women >60 years of age exceeds 71% of participants with at least 1 risk factor (1). We observed that significant CAC is found in 25% of women enrolled in RCTs of DES and was independently associated with a variety of other known cardiovascular risk factors. This numeric difference could be explained by the method by which calcification was assessed (coronary angiography vs. computed tomography), by different grading in CAC severity, and because many DES trials have severe coronary calcification as an exclusion criterion. In addition, evaluation of CAC with computed tomography allows a more accurate morphological characterization and quantification of CAC, which has been demonstrated to provide superior risk stratification with high net reclassification index to predict future coronary events (3). The independent clinical correlates of CAC identified in this purely female population are in line with previous translational studies investigating the pathophysiology of arterial calcifications (14). As identified in the fully adjusted model, age, hypertension, hypercholesterolemia, and smoking, alongside the metabolic abnormalities induced by worsening renal function, have been all described as factors implicated in the pathogenesis of CAC (1,14).
In our study, the presence of significant CAC was independently associated with increased risk for major adverse cardiac events at follow-up, including spontaneous MI, TLR, and mortality. Lesions that are calcified are usually chronic, stable, and stiff, leading to stent underexpansion, eventually increasing the risk for ST, in-stent restenosis, and future need for TLR, across the entire clinical spectrum of CAD (15,16). A patient-level pooled analysis of 6,855 patients from the ACUITY (Acute Catheterization and Urgent Intervention Triage Strategy) and HORIZONS-AMI (Harmonizing Outcomes With Revascularization and Stents in Acute Myocardial Infarction) trials evaluated the impact of coronary calcification on ischemic outcomes undergoing PCI and presenting with acute coronary syndromes. At 1 year, coronary calcification was independently associated with ST, TLR, and mortality (4). Bourantas et al. (17), in a patient-level pooled analysis of 7 RCTs and 6,269 patients, found that the presence of severe CAC was a powerful predictor of major adverse events, even when adjusting for underlying CAD complexity (including the SYNTAX [Synergy Between PCI With Taxus and Cardiac Surgery] score) (17). In all of these previous studies, the prevalence of women was relatively low (<25% to 30%), thereby precluding the generalizability of the findings in a female population. Our findings extend previous observations made in predominantly male populations and consolidate the role of CAC as a marker of future ischemic risk in women undergoing percutaneous revascularization.
Cardiac ischemic events in women with significant CAC can be categorized as stent-related and non-stent-related. Regarding stent-related adverse events, the presence of CAC was independently associated with an increased risk for TLR over 3 years of follow-up. However, when we checked the temporal consistency of the effect of CAC, the risk for TLR appeared to be increased within the first year (early and late periods), while there were no significant differences between 1 and 3 years. It is plausible that the effect of target lesion CAC on TLR is mostly mediated by the higher risk for acute or early device failure (due to DES underexpansion or malapposition), with subsequent risk for repeated revascularization early after index PCI; conversely, the very late risk for TLR might be associated mostly with the development of in-stent neointimal hyperplasia and/or neoatherosclerosis (18). Regarding non-stent-related adverse events, we observed an adjusted increase in risk for spontaneous MI in women with significant CAC. Indeed, the presence of CAC appeared to be correlated with greater extent of coronary and systemic atherosclerosis (1,13). However, whether calcified lesions constitute the substrate for future atherothrombotic events remain unclear. In a subanalysis from the PROSPECT (Providing Regional Observations to Study Predictors of Events in the Coronary Tree) study, the presence of calcified nodules within the coronary tree in patients presenting with ACS was associated with more nonculprit lesions, longer lesions, greater plaque burden, and more thick-cap fibroatheromas (19). Of note, calcified nodules were not independently associated with increased risk for nonculprit lesion–related major adverse cardiac events at follow-up (as opposed to thin-cap fibroatheromas), suggesting that lesions with calcific features do not necessarily represent plaques at higher risk for progression and atherothrombosis.
The harmful effect of CAC on ischemic risk was uniform across specific clinical and angiographic subgroups, including new-generation DES. New-generation DES platforms significantly improved the efficacy and safety of PCI compared with bare-metal stents and early-generation DES, especially in terms of late and very late thrombotic safety (7–10,20). However, whether the antithrombotic and antirestenotic properties of new-generation DES are preserved in challenging subsets of lesions is unclear. In the present study, the effect of CAC on composite major adverse events and device-oriented endpoints (TLR and ST) was uniform across DES generations, suggesting that in the presence of significant calcified lesions, PCI outcomes remain suboptimal even with newer DES technologies. Whether lesion decalcification may improve PCI outcomes prior to DES implantation is under investigation. Recently the prospective, multicenter, single-arm ORBIT-II (Evaluate the Safety and Efficacy of Orbital Atherectomy System in Treating Severely Calcified Coronary Lesions) study reported favorable DES implantation success (residual stenosis <50% post-stent without in-hospital major adverse cardiac events) and 30-day and 1-year ischemic outcomes with the Diamondback 360 Coronary Orbital Atherectomy System (Cardiovascular Systems, St. Paul, Minnesota) in patients with severely calcified target lesions. Lesion preparation and stent implantation optimization will be even more important in the era of bioresorbable scaffolds, with which even with meticulous lesion preparation, optimal stent expansion and strut apposition are not always achieved (21). Whether routine lesion decalcification is associated with improved PCI outcomes needs to be demonstrated in appropriately designed RCTs.
The trials included in the analysis span over a decade, during which there have been major advances in interventional approach and technologies, that could affect subsequent outcomes (especially the use of rotational atherectomy to optimize DES implantation). Differences among studies were accounted for by including trial identifier as a random effect in the adjusted analyses; however, residual confounding may remain.
Second, patient populations included in the 26 pooled trials had some heterogeneity resulting from the variability in inclusion and exclusion criteria. Early trials included patients with stable CAD and single lesions, and later trials were more inclusive by including also more complex patients with multivessel disease and acute coronary syndromes.
Third, for a significant number of studies, severe calcification was an exclusion criterion, thus limiting the external validity of our findings.
Fourth, the exclusion of data for male participants from this analysis precluded sex-specific analyses. Consequently, we are unable to comment on whether there is a difference in outcomes between the sexes after PCI according to CAC severity.
Fifth, interobserver and intraobserver quantitative coronary angiographic core laboratory variability across trials was not available.
Sixth, data regarding dual-antiplatelet therapy duration and intensity, which influence ischemic and bleeding outcomes (particularly per DES generation) (22,23), and data regarding statin use (which demonstrated to modify coronary plaque composition) (24) were not available.
Finally, because the included trials were not designed to investigate the safety and efficacy of DES in women with calcified lesions, the results of this post hoc analysis must be considered hypothesis generating.
Women with moderate or severe CAC undergoing PCI with DES display a higher clinical risk profile and remain at higher risk for midterm (1 year) to long-term (3 years) major adverse cardiovascular events, including mortality. The adverse effect of CAC on ischemic outcomes appears to be uniform across clinical and angiographic subsets, including new-generation DES. Additional measures to mitigate coronary ischemic risk and improve suboptimal device-oriented outcomes in this patient population are warranted and merit further investigation.
WHAT IS KNOWN? The presence of CAC confers increased risk for stent-related and non-stent-related coronary thrombotic events. However, previous studies were performed in predominantly male populations.
WHAT IS NEW? Women with CAC tend to have a worse clinical risk profile compared with those without CAC. In women undergoing DES implantation, the presence of CAC was associated with increased risk for long-term stent-related and non-stent-related cardiac ischemic events. The increased risk associated with the presence of CAC was uniform across clinical presentations and DES generations.
WHAT IS NEXT? CAC is a useful biometric to predict future atherothrombotic risk in women with CAD requiring revascularization. Measures to mitigate the increased risk for stent-related adverse events associated with the presence of CAC are warranted.
The Gender Data Forum was sponsored by the WIN initiative of the Society for Cardiovascular Angiography and Interventions.
For supplemental tables, please see the online version of this article.
Dr. Stefanini has received speaking fees from Abbott Vascular, AstraZeneca, Biosensors, and Biotronik. Dr. Windecker has received research contracts to the institution from Abbott Vascular, Boston Scientific, Biosensors, Cordis, and Medtronic. Dr. Wijns has received institutional research grants from Boston Scientific, Medtronic, Abbott Vascular, Terumo, and Biosensors; and is an investigator for trials sponsored by Boston Scientific, Medtronic, Abbott Vascular, Terumo, and Biosensors. Fees or honoraria on behalf of Dr. Wijns from Boston Scientific, Medtronic, Abbott Vascular, Terumo, and Biosensors go to the Cardiovascular Center Aalst. Dr. Von Birgelen is a consultant to and has received lecture fees or travel expenses from Abbott Vascular, Biotronik, Boston Scientific, Medtronic, and Merck Sharp and Dohme. Dr. Von Birgelen’s research department, Thoraxcentrum Twente, has received educational or research grants from Abbott Vascular, Biotronik, Boston Scientific, and Medtronic. Dr. Kandzari has received research or grant support from Medtronic, Abbott Vascular, and Boston Scientific; and consulting honoraria from Medtronic and Boston Scientific. 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 Medical, and Abbott Vascular; and honoraria for lectures from Cordis, Carbostent and Implantable Devices, and Terumo. Dr. Galatius has received grant support from St. Jude Medical, Abbott Vascular, Terumo, and Biotronik; and advisory board honoraria from Eli Lilly and Servier. Dr. Smits has received institutional research grants from Abbott Vascular, Boston Scientific, St. Jude Medical, and Terumo. Dr. Steg has received research grants (to INSERM U1148) from Servier and Sanofi; has served as a speaker or consultant for Amarin, AstraZeneca, Bayer, Boehringer-Ingelheim, Bristol-Myers Squibb, Daiichi-Sankyo, GlaxoSmithKline, Janssen, Eli Lilly, Medtronic, Merck-Sharpe Dohme, Novartis, Orexigen, Pfizer, Regado, Sanofi, Servier, and The Medicines Company; and is a stockholder of Aterovax. Dr. Kastrati has received honoraria from Abbott Vascular, Biosensors, Biotronik, Cordis, and Medtronic; and a patent application with respect to a biodegradable polymer stent coating. Dr. Mehran has received institutional research grant support from The Medicines Company, Bristol-Myers Squibb, Sanofi, Eli Lilly, and AstraZeneca; and consulting fees from AstraZeneca, Bayer, CSL Behring, Janssen Pharmaceuticals, Merck, Osprey Medical, and Watermark Research Partners; and serves on the advisory boards of Abbott Laboratories, Boston Scientific, 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.
- Abbreviations and Acronyms
- coronary artery calcification
- coronary artery disease
- confidence interval
- drug-eluting stent(s)
- hazard ratio
- myocardial infarction
- percutaneous coronary intervention
- randomized controlled trial
- stent thrombosis
- target lesion revascularization
- Received April 5, 2016.
- Revision received May 17, 2016.
- Accepted June 16, 2016.
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