Author + information
- Received February 23, 2015
- Revision received March 2, 2015
- Accepted March 4, 2015
- Published online May 26, 2015.
- Robert W. Yeh, MD, MSc∗,†,‡,
- Dean J. Kereiakes, MD§,
- Philippe Gabriel Steg, MD‖,¶,#,
- Stephan Windecker, MD∗∗,
- Michael J. Rinaldi, MD††,
- Anthony H. Gershlick, MBBS‡‡,
- Donald E. Cutlip, MD†,‡,§§,
- David J. Cohen, MD, MSc‖‖,
- Jean-Francois Tanguay, MD¶¶,
- Alice Jacobs, MD##,
- Stephen D. Wiviott, MD‡∗∗∗,
- Joseph M. Massaro, PhD†,†††,
- Adrian C. Iancu, MD‡‡‡,
- Laura Mauri, MD, MSc†,‡∗∗∗∗ (, )
- DAPT Study Investigators
- ∗Massachusetts General Hospital, Boston, Massachusetts
- †Harvard Clinical Research Institute, Boston, Massachusetts
- ‡Harvard Medical School, Boston, Massachusetts
- §The Christ Hospital Heart and Vascular Center and The Lindner Center for Research and Education, Cincinnati, Ohio
- ‖Université Paris-Diderot, Paris, France, INSERM U-1148, Paris, France
- ¶Hôpital Bichat, Département Hospitalo-Universitaire FIRE, Assistance Publique–Hôpitaux de Paris, Paris, France
- #NHLI, Imperial College, Royal Brompton Hospital, London, United Kingdom
- ∗∗Bern University Hospital, Bern, Switzerland
- ††The Sanger Heart and Vascular Institute, Carolinas HealthCare System, Charlotte, North Carolina
- ‡‡Department of Cardiovascular Sciences, University of Leicester and National Institute of Health Research Leicester Cardiovascular Biomedical Research Unit, University Hospitals of Leicester, Leicester, United Kingdom
- §§Beth Israel Deaconess Medical Center, Boston, Massachusetts
- ‖‖Saint Luke’s Mid-America Heart Institute, University of Missouri–Kansas City School of Medicine, Kansas City, Missouri
- ¶¶Montreal Heart Institute, Université de Montréal, Montreal, Canada
- ##Boston Medical Center, Boston University School of Medicine, Boston, Massachusetts
- ∗∗∗Brigham and Women’s Hospital, Boston, Massachusetts
- †††Boston University School of Public Health, Boston, Massachusetts
- ‡‡‡Heart Institute, University of Medicine Iuliu Hatieganu, Cluj Napoca, Romania
- ↵∗Reprint requests and correspondence:
Dr. Laura Mauri, Division of Cardiovascular Medicine, Department of Medicine, Brigham and Women’s Hospital, 75 Francis Street, Boston, Massachusetts 02115.
Background The benefits and risks of prolonged dual antiplatelet therapy may be different for patients with acute myocardial infarction (MI) compared with more stable presentations.
Objectives This study sought to assess the benefits and risks of 30 versus 12 months of dual antiplatelet therapy among patients undergoing coronary stent implantation with and without MI.
Methods The Dual Antiplatelet Therapy Study, a randomized double-blind, placebo-controlled trial, compared 30 versus 12 months of dual antiplatelet therapy after coronary stenting. The effect of continued thienopyridine on ischemic and bleeding events among patients initially presenting with versus without MI was assessed. The coprimary endpoints were definite or probable stent thrombosis and major adverse cardiovascular and cerebrovascular events (MACCE). The primary safety endpoint was GUSTO (Global Utilization of Streptokinase and Tissue Plasminogen Activator for Occluded Arteries) moderate or severe bleeding.
Results Of 11,648 randomized patients (9,961 treated with drug-eluting stents, 1,687 with bare-metal stents), 30.7% presented with MI. Between 12 and 30 months, continued thienopyridine reduced stent thrombosis compared with placebo in patients with and without MI at presentation (MI group, 0.5% vs. 1.9%, p < 0.001; no MI group, 0.4% vs. 1.1%, p < 0.001; interaction p = 0.69). The reduction in MACCE for continued thienopyridine was greater for patients with MI (3.9% vs. 6.8%; p < 0.001) compared with those with no MI (4.4% vs. 5.3%; p = 0.08; interaction p = 0.03). In both groups, continued thienopyridine reduced MI (2.2% vs. 5.2%, p < 0.001 for MI; 2.1% vs. 3.5%, p < 0.001 for no MI; interaction p = 0.15) but increased bleeding (1.9% vs. 0.8%, p = 0.005 for MI; 2.6% vs. 1.7%, p = 0.007 for no MI; interaction p = 0.21).
Conclusions Compared with 12 months of therapy, 30 months of dual antiplatelet therapy reduced the risk of stent thrombosis and MI in patients with and without MI, and increased bleeding. (The Dual Antiplatelet Therapy Study [The DAPT Study]; NCT00977938)
- acute coronary syndromes
- antiplatelet therapy
- myocardial infarction
- percutaneous coronary intervention
- randomized clinical trial
Treatment with dual antiplatelet therapy using the combination of a P2Y12 receptor inhibitor and aspirin is mandatory after percutaneous coronary intervention (PCI) with stents. In the Dual Antiplatelet Therapy (DAPT) Study, patients who were free from major ischemic or bleeding events at 1 year after PCI had significant reductions in stent thrombosis and myocardial infarction (MI) but increases in moderate or severe bleeding when treated with continued dual antiplatelet therapy for a total of 30 months as compared with 12 months (1). Patients presenting with acute MI may derive particular benefit from treatment with extended-duration dual antiplatelet therapy, because of a greater risk of subsequent MI and stent thrombosis (2,3). Consequently, current guidelines generally recommend a longer treatment period in patients undergoing PCI for MI regardless of stent type (bare-metal stent [BMS] or drug-eluting stent [DES]) compared with those undergoing PCI for less acute indications (4–6).
However, patients with stable coronary disease are also at risk for future acute ischemic events, and may also benefit from prolonged dual antiplatelet therapy (7). Whether those undergoing PCI for MI derive a similar or greater benefit from continued thienopyridine treatment beyond 12 months compared with those undergoing PCI for more stable presentations is unknown. We therefore compared the treatment effect of 30 versus 12 months of dual antiplatelet therapy after coronary stenting among subjects who presented with and without acute MI.
The DAPT Study design has previously been described (8). Briefly, this double-blind, international, multicenter, randomized, placebo-controlled trial compared the benefits and risks of 30 versus 12 months of thienopyridine therapy (clopidogrel or prasugrel) when prescribed in addition to aspirin following coronary stenting with either DES or BMS. The trial incorporated five individual component studies into a single, uniform randomized trial, with enrollment of subjects either by the Harvard Clinical Research Institute or through 1 of 4 post-marketing surveillance studies. The results comparing randomized treatments in the overall DES-treated (1) and BMS-treated (9) cohorts have been reported previously. The institutional review board at each participating institution approved the study. The purpose of the present study was to examine whether the ischemic benefits and bleeding risks associated with 30 versus 12 months of dual antiplatelet therapy are consistent among patients presenting with versus without acute MI. These analyses were not pre-specified in the original protocol.
Study population and procedures
We enrolled patients with coronary artery disease who were candidates for dual antiplatelet therapy and who received treatment with Food and Drug Administration–approved DES and BMS devices. Patients provided written informed consent and were enrolled within 3 days of stent placement. Stent treatment was performed according to site standards of care. DES types included sirolimus-eluting stent (Cypher, Cordis, Bridgewater, New Jersey), zotarolimus-eluting stent (Endeavor, Medtronic, Minneapolis, Minnesota), paclitaxel-eluting stent (TAXUS, Boston Scientific, Marlborough, Massachusetts), and everolimus-eluting stents (Xience, Abbott Vascular, Santa Clara, California; PROMUS, Boston Scientific). For this analysis, all randomized DES- and BMS-treated patients were included.
All patients received open-label aspirin plus thienopyridine for the first 12 months after stent implantation. In 1 of the contributing studies (10), all patients received prasugrel under an Investigational Device Exemption from the Food and Drug Administration. In the remaining 4 contributing studies, the selection of thienopyridine was left to the discretion of the treating physician. At 12 months, patients who had not had a major adverse cardiovascular or cerebrovascular event (MACCE) (defined as the composite of death, MI, or stroke), repeat revascularization, or moderate or severe bleeding and had been compliant with thienopyridine therapy (defined as having taken 80% to 120% of the drug without an interruption of longer than 14 days) were randomized in a 1:1 ratio to continued thienopyridine or to placebo for an additional 18 months. Both groups continued aspirin therapy.
Computer-generated randomization was stratified according to stent type (DES vs. BMS), hospital site, thienopyridine type, and presence or absence of at least 1 pre-specified clinical- or lesion-related stent thrombosis risk factor, including presentation with MI (8). Acute MI at the time of PCI was defined as the presence of ischemic symptoms at rest and lasting >10 minutes before index procedure and/or electrocardiogram evidence of ischemia, in conjunction with elevated levels of a cardiac biomarker of necrosis (creatine kinase-MB or troponin T or I greater than the upper limit of normal). If creatine kinase-MB or troponin was not available, total creatine kinase >2 times the upper limit of normal was also considered to constitute MI.
The coprimary effectiveness endpoints of the DAPT Study were the incidence of definite or probable stent thrombosis according to the Academic Research Consortium definitions (11) and incidence of MACCE in all randomized patients at 12 to 30 months post-index procedure. The primary safety endpoint was moderate or severe bleeding during this same time period as assessed according to the GUSTO (Global Utilization of Streptokinase and Tissue Plasminogen Activator for Occluded Arteries) classification (12). Bleeding was also ascertained according to the Bleeding Academic Research Consortium definitions (13). Secondary endpoints of the study included MI, according to the Academic Research Consortium definition, which was further segregated into those occurring in association with stent thrombosis and those not related to stent thrombosis.
All potential endpoint events were adjudicated by an independent Clinical Events Committee masked to treatment assignment. An independent central Data Safety Monitoring Board reviewed data from all subjects at regular intervals.
We compared Kaplan-Meier estimates of endpoint events occurring between 12 and 30 months after PCI among patients with and without acute MI at presentation, irrespective of treatment arm using the log-rank test. Patients not experiencing the coprimary endpoints 12 to 30 months post-index procedure were censored at the time of last known contact or 30 months, whichever was earlier.
Kaplan-Meier estimates of endpoint events were also generated for each treatment arm among patients with and without MI. The effects of continued thienopyridine versus placebo for patients with and without MI were assessed using Cox proportional hazards regression models, and are expressed as hazard ratios (HRs) and associated 95% confidence intervals (CIs). The consistency of the treatment effect between patients with and without MI was evaluated through the inclusion of randomized treatment-by-MI status interaction terms. Furthermore, among patients with and without MI, exploratory sensitivity analyses were performed to assess the consistency of treatment effect among DES- versus BMS-treated patients for stent thrombosis, and among patients treated with clopidogrel versus prasugrel at randomization for stent thrombosis, MI, and bleeding. Finally, for the endpoints of stent thrombosis and MI, additional analyses were performed excluding paclitaxel-eluting stents, which have been associated with higher rates of adverse stent-related ischemic events compared with other DESs (14).
All analyses were performed on randomized subjects according to the intention-to-treat principle. All statistical analyses were conducted at Harvard Clinical Research Institute with the use of SAS version 9.2 (SAS Institute Inc., Cary, North Carolina). A 2-sided p value of 0.05 or less was considered statistically significant for all analyses.
Role of the funding source
The stent manufacturers who funded the trial had contributing roles in the design of the trial and in the collection of the data. Harvard Clinical Research Institute was responsible for the scientific conduct of the trial and independent analysis of the data. RWY, JMM, and LM had full access to all the data used in the study, and the study publications committee (including RWY, DJK, JMM, and LM) had final responsibility for the decision to submit for publication.
Of 11,648 patients randomized in the DAPT Study, 3,576 (30.7%) presented with acute MI with the remainder presenting without evidence of MI at the index procedure (Figure 1). Among MI patients, 1,680 (47%) presented with initial ST-elevation MI, whereas the remainder presented with non–ST-elevation MI. Among patients with no MI, 1,821 (22.6%) were classified as having unstable angina without cardiac biomarker elevation.
Patients with MI had higher rates of smoking, whereas patients with no MI were older (average age, 63 vs. 58 years; p < 0.001); more often female; and had higher rates of diabetes, peripheral arterial disease, and prior PCI. Characteristics were evenly balanced across randomization arms for patients with and without MI (Table 1). Rates of prasugrel use at randomization were higher among patients with MI compared with those without (34.0% vs. 30.6%, respectively; p < 0.001). Among patients with MI, 27.6% received BMS only and 72.4% received DES, compared with 8.7% and 91.3%, respectively, among patients with no MI. Lesions were less complex among patients with MI, with lower rates of heavy calcification, tortuosity, and left main and in-stent restenosis lesions.
Outcomes comparing patients with versus without acute MI
Patients presenting with MI had significantly higher rates of definite or probable stent thrombosis (1.2% vs. 0.7%; p = 0.01) between 12 and 30 months than patients without MI (Table 2). Rates of MACCE were similar for patients with versus without MI (5.4% vs. 4.9%; p = 0.24). Among the components of MACCE, rates of subsequent MI were higher for patients with MI compared with those without MI (3.7% vs. 2.8%; p = 0.01) (Figure 2B), which was primarily related to higher rates of stent-thrombosis–associated MI (1.2% vs. 0.7%; p = 0.005). The rates of death and stroke were no different between patients with versus without MI. In both groups, nonfatal MI was the predominant contributor to MACCE in follow-up, accounting for 69% of events in the MI group, and 57% of events in the no MI group.
GUSTO moderate or severe bleeding occurred less often in patients with MI (1.4%) as compared with those without (2.1%; p = 0.008) between 12 and 30 months after initial presentation. Similar results were observed on the basis of classification by the Bleeding Academic Research Consortium definitions. Fatal bleeding was rare and not significantly different between patients with versus without MI (0.17% vs. 0.08%; p = 0.15).
Consistency of treatment effect of continued thienopyridine in patients presenting with and without MI
The relative reduction of stent thrombosis associated with continued thienopyridine was similar for patients with and without MI (interaction p = 0.69 for stent thrombosis) (Figure 2). In patients with MI, the rate of stent thrombosis was 0.5% for continued thienopyridine versus 1.9% for placebo (HR: 0.27; 95% CI: 0.13 to 0.57; p < 0.001), whereas for patients with no MI, the corresponding rates were 0.4% versus 1.1%, respectively (HR: 0.33; 95% CI: 0.18 to 0.60; p < 0.001). For the composite endpoint of MACCE, continued thienopyridine was associated with a similar directional benefit but greater magnitude reductions for patients with MI (3.9% vs. 6.8%; HR: 0.56; 95% CI: 0.42 to 0.76; p < 0.001) compared with those without MI (4.4% vs. 5.3%; HR: 0.83; 95% CI: 0.68 to 1.02; p = 0.08; interaction p = 0.03) (Figure 3).
Continued thienopyridine consistently reduced MI in patients with and without MI (interaction p = 0.15) (Central Illustration). Among patients with MI, the rate of MI was 2.2% for continued thienopyridine versus 5.2% for placebo (HR: 0.42; 95% CI: 0.29 to 0.62; p < 0.001). In patients with no MI, the rate of MI was 2.1% for continued thienopyridine versus 3.5% for placebo (HR: 0.60; 95% CI: 0.45 to 0.79; p < 0.001). For both groups, the reduction in MI was related to the prevention of both stent thrombosis- and nonstent thrombosis-related events (Table 3).
Continued thienopyridine increased major bleeding in both patients with MI (1.9% vs. 0.8%; HR: 2.38; 95% CI: 1.28 to 4.43; p = 0.005) and those without MI (2.6% vs. 1.7%; HR: 1.53; 95% CI: 1.12 to 2.08; p = 0.007; p = 0.21 for interaction). Among patients with MI, the rates of all-cause death were 1.4% in the continued therapy group versus 1.6% in the placebo group (HR: 0.87; 95% CI: 0.50 to 1.50; p = 0.61). Among patients with no MI, the rates of death were 2.1% for continued thienopyridine group versus 1.5% for placebo (HR: 1.43; 95% CI: 1.02 to 2.00; p = 0.04; effect for MI vs. no MI interaction p = 0.13).
In patients with and without MI, reduction in stent thrombosis with continued thienopyridine was consistent for DES-treated patients and BMS-treated patients (interaction p = 0.87 for MI patients; interaction p = 0.12 for no MI patients) (Online Tables 1 to 6). Continued thienopyridine was also associated with consistent reductions in stent thrombosis and MI across different thienopyridine types, prasugrel and clopidogrel (MI patients: interaction p = 0.86 for stent thrombosis, interaction p = 0.22 for MI; no MI patients: interaction p = 0.97 for stent thrombosis, interaction p = 0.10 for MI for patients without MI). Moderate or severe bleeding with continued thienopyridine was also increased to a similar degree with prasugrel or clopidogrel among patients with MI (interaction p = 0.09) and those without MI (interaction p = 0.13). Finally, when excluding patients who received paclitaxel-eluting stents, the results were similar to the main study findings, with continued thienopyridine having a similar effect on stent thrombosis (interaction p = 0.34) and MI (interaction p = 0.57) for patients with and without MI.
In this analysis from the DAPT Study, patients presenting with acute MI who survived the first year after PCI without a major ischemic or bleeding event continued to be at higher risk for subsequent ischemic events, including stent thrombosis and MI, compared with those presenting without MI. Continued thienopyridine therapy beyond 12 months was associated with significant reductions in stent thrombosis and MI and an increase in bleeding in both groups.
These findings have important implications for the management of dual antiplatelet therapy in patients undergoing PCI. As demonstrated here and in prior studies, patients presenting with MI represent a subgroup that continues to experience higher rates of stent thrombosis and MI more than 1 year removed from their initial event (2). As such, MI patients are among those that may derive particular benefit from extension of thienopyridine therapy. Current guidelines recommend only a year of dual antiplatelet therapy after an acute coronary event (4–6). Our data suggest that if patients undergoing PCI after MI have not experienced a major ischemic or bleeding event within the first year of follow-up, continuation of dual antiplatelet therapy beyond 1 year is associated with a reduced risk of stent thrombosis and MI. Continued thienopyridine therapy over an 18-month treatment period was associated with an absolute risk reduction of 2.9% for MI and 1.4% for stent thrombosis, and an absolute risk increase of 1.1% for moderate or severe bleeding (0.9% for moderate and 0.2% for severe) among patients with MI.
Patients undergoing PCI without MI had lower long-term ischemic event rates compared with MI patients, yet the reduction in stent thrombosis and MI with continued dual antiplatelet therapy was consistent among patients not presenting with MI. Compared with 12 months of treatment, continued thienopyridine for 30 months was associated with an absolute risk reduction of 1.4% for MI and 0.7% for stent thrombosis, and an absolute risk increase of 0.9% for moderate or severe bleeding (0.6% for moderate and 0.3% for severe) in this population.
A lesser magnitude reduction in MACCE was observed with continued thienopyridine therapy among patients without compared with those with MI at presentation, caused in part by the overall lower rates of nonfatal MI in follow-up among patients without MI, but also by an increase in death for patients without MI receiving continued thienopyridine. As previously described (1), a higher rate of noncardiovascular death was observed among DES-treated patients assigned to continued thienopyridine. Masked adjudication of all noncardiovascular deaths determined that most of these deaths were not preceded by a documented bleeding event. A meta-analysis of more than 69,000 patients from randomized clinical trials comparing different durations of dual antiplatelet therapy across a variety of clinical indications, including more than 39,000 patients with coronary artery disease, showed no association between thienopyridine therapy and all-cause or noncardiovascular death (15), suggesting that the findings among DES patients, concentrated among those without MI, may have been caused by chance. Patients without MI were older and had more comorbidities (diabetes, peripheral and cerebrovascular disease). These factors may have led to the higher proportion of noncardiac events in patients without MI; it is also possible that these factors contributed to more frequent bleeding events in this same group.
In light of greater reduction in quality of life expectancy associated with major ischemic events, as compared with bleeding events of this frequency and magnitude (16), our results suggest that among acute MI patients undergoing PCI, there is a strong benefit for continuing thienopyridine therapy beyond 12 months after presentation. However, even among patients without MI, the risk-benefit balance may favor continuation of thienopyridine therapy beyond 12 months for those who are able to tolerate the first year of dual antiplatelet therapy. The results also suggest that the benefits of continued thienopyridine therapy observed in patients with and without MI were consistent whether or not patients received clopidogrel or prasugrel, or whether they received paclitaxel- or non–paclitaxel-eluting stents. Furthermore, the benefit of receiving continued thienopyridine therapy in patients with and without MI was in the prevention of nonfatal MI in follow-up, both related to and not related to stent thrombosis. The absolute reduction in nonstent thrombosis-related MI was 1.5% in the MI group and 0.6% in the no MI group, accounting for roughly one-half of the reduction in nonfatal MI in both groups. These findings suggest that continued thienopyridine therapy has an important effect beyond stent thrombosis on secondary prevention of future MIs after PCI.
Several prior analyses have compared different durations of dual antiplatelet therapy after coronary stent procedures (17–21) including examining the consistency of treatment effects on patients with and without acute coronary syndromes (22). However, the DAPT study is unique in several regards. First, it is the largest study to date, having been powered to examine rare events, such as stent thrombosis. Next, patients enrolled in the DAPT Study comprised a broad range of presentations (23), including a very high proportion with acute coronary syndromes, including ST-segment elevation MI, allowing for more precise estimates of the effect of continued thienopyridine therapy in high-risk patients similar to those seen in clinical practice. The study population represents the largest cohort to date to evaluate the effect of continued thienopyridine therapy after coronary stents in patients with and without MI.
Beyond randomized studies focused on coronary stents, the largest prior study of extended duration clopidogrel in subjects with symptomatic, but stable, cardiovascular disease or risk factors for cardiovascular disease was negative regarding reduction in cardiovascular risk (7). Within this trial, the subset of patients with prior documented symptomatic cardiovascular disease (mainly coronary artery disease) appeared to benefit from extended therapy (24), whereas the asymptomatic subset did not. Our results are consistent with these prior results, and suggest that among symptomatic patients with coronary artery disease, prolonged thienopyridine therapy may provide ischemic benefit. Notably, in the DAPT Study, subjects without MI represented a higher-risk population than subjects studied in prior trials of stable angina, because the group included a large number of subjects with unstable angina, all with history of prior coronary revascularization procedures, and with concomitant cardiac risk factors. These findings suggest that patients previously considered “stable” a full year removed from PCI for acute or stable presentations are still subject to preventable risks of future MI, not directly related to the stent procedure. The 1-year follow-up after coronary stenting thus provides an important contact in which to intervene to continue thienopyridine therapy in those subjects who have tolerated treatment without major bleeding.
First, because the study randomized only those patients who did not sustain a major event during the first year after PCI and were compliant with therapy, the study results are only relevant to patients who have achieved a similar milestone. Next, the study only included thienopyridine P2Y12 inhibitors; a related randomized study of a different P2Y12 inhibitor, ticagrelor, found that subjects with prior MI benefited from extended dual antiplatelet therapy with this agent (25). We conducted several exploratory analyses examining the consistency of the treatment effect of continued thienopyridine on the basis of stent type and drug type. However, these analyses were not pre-specified or specifically powered to assess interactions, and should therefore be interpreted accordingly. Finally, the results shown represent aggregated findings for patients with and without MI. Additional risk factors may help to identify smaller subgroups of patients who may experience a different balance in the risks and benefits of continued thienopyridine therapy after 12 months.
The continuation of thienopyridine-plus-aspirin therapy beyond 1 year after coronary stenting reduced ischemic events in patients both with and without acute MI at presentation, but increased bleeding compared with treatment with aspirin alone. Although patients presenting with MI had higher risks of subsequent ischemic events, the effect of continued treatment in reducing stent thrombosis and MI was nevertheless consistent among patients not presenting with MI.
COMPETENCY IN SYSTEMS-BASED PRACTICE: Continuation of thienopyridine therapy beyond 12 months after coronary stent implantation reduces stent thrombosis and myocardial infarction in patients with acute coronary syndromes or stable ischemic heart disease undergoing percutaneous revascularization, but increases the risk of bleeding.
TRANSLATIONAL OUTLOOK: Further studies are needed to identify individual patient characteristics associated with thrombotic and hemorrhagic events to guide individualized decisions on the duration of dual antiplatelet therapy for patients in specific clinical situations.
The authors acknowledge Ms. Priscilla Driscoll-Schempp, Ms. Wen-Hua Hsieh, and Ms. Joanna Suomi for their important contributions to this study.
For supplemental tables, please see the online version of this article.
This research is sponsored by the Harvard Clinical Research Institute and funded by Abbott, Boston Scientific Corporation, Cordis Corporation, Medtronic, Inc., Bristol-Myers Squibb Company/Sanofi Pharmaceuticals Partnership, Eli Lilly and Company, and Daiichi-Sankyo Company Limited, and the U.S. Department of Health and Human Services (1RO1FD003870-01). Dr. Yeh is on the advisory board of Abbott Vascular; and has received consulting fees from Gilead Sciences and Merck. Dr. Kereiakes has served as a consultant for Boston Scientific and Abbott Vascular. Dr. Steg has received personal fees from Amarin, AstraZeneca, Bayer, Boehringer-Ingelheim, Bristol-Myers Squibb, Daiichi-Sankyo, GlaxoSmithKline, Eli Lilly, Merck-Sharpe-Dohme, Novartis, Otsuka, Pfizer, Roche, Medtronic, Sanofi, Servier, Vivus, Janssen, The Medicines Company, and Orexigen; and has received grants from Sanofi and Servier. Dr. Windecker has received research grants to the institution from Abbott, Biotronik, Boston Scientific, Edwards Lifesciences, Medtronic, The Medicines Company, and St. Jude; and speaker fees from AstraZeneca, Eli Lilly, Abbott, Biotronik, Boston Scientific, Bayer, and Biosensors. Dr. Gershlick has received personal fees from Medtronic and Abbott; and grants from The Medicines Company. Dr. Cutlip has received other fees from Medtronic, Boston Scientific, Cordis Inc., and Abbott Vascular; and grants from the National Heart, Lung, and Blood Institute during the conduct of the study. Dr. Cohen has received research grant support to the institution from Eli Lilly, AstraZeneca, Daiichi-Sankyo, Abbott Vascular, Boston Scientific, and Medtronic; and consulting fees from Eli Lilly, AstraZeneca, Abbott Vascular, and Medtronic. Dr. Tanguay has received personal fees and other from Abbott Vascular, AstraZeneca, Bristol-Myers Squibb, Eli Lilly, GlaxoSmithKline, and Sanofi; personal fees from Bayer, Roche, and Servier; and other fees from Ikaria and Merck. Dr. Wiviott has received grants and personal fees from AstraZeneca, Bristol-Myers Squibb, Arena, and Eli Lilly/Daiichi-Sankyo; grants from Eisai, Merck, and Sanofi; and personal fees from Aegerion, Angelmed, Janssen, Xoma, ICON Clinical, and the Boston Clinical Research Institute. Dr. Massaro has received personal fees from the Harvard Clinical Research Institute during the conduct of the study. Dr. Mauri has received institutional research grants from Abbott, Boston Scientific, Cordis, Medtronic, Eli Lilly/Daiichi-Sankyo, and Sanofi/Bristol-Myers Squibb; and personal fees from Medtronic, Recor, St. Jude Medical, and Biotronik. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.
P. K. Shah, MD, served as Guest Editor for this paper.
- Abbreviations and Acronyms
- bare-metal stent(s)
- confidence interval
- drug-eluting stent(s)
- hazard ratio
- major adverse cardiovascular and cerebrovascular events(s)
- myocardial infarction
- percutaneous coronary intervention
- Received February 23, 2015.
- Revision received March 2, 2015.
- Accepted March 4, 2015.
- American College of Cardiology Foundation
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