Author + information
- Received June 10, 2016
- Accepted June 19, 2016
- Published online September 26, 2016.
- Jérémie Abtan, MDa,
- P. Gabriel Steg, MDa,b,∗ (, )
- Gregg W. Stone, MDc,
- Kenneth W. Mahaffey, MDd,
- C. Michael Gibson, MDe,
- Christian W. Hamm, MDf,
- Matthew J. Price, MDg,
- Freddy Abnousi, MD, MBA, MScg,
- Jayne Prats, PhDh,
- Efthymios N. Deliargyris, MDh,
- Harvey D. White, DSci,
- Robert A. Harrington, MDd,
- Deepak L. Bhatt, MD, MPHj,
- CHAMPION PHOENIX Investigators∗
- aDHU (Département Hospitalo-Universitaire)-FIRE (Fibrosis, Inflammation, REmodelling), Hôpital Bichat, AP-HP (Assistance Publique-Hôpitaux de Paris), Université Paris-Diderot, Sorbonne-Paris Cité, and FACT (French Alliance for Cardiovascular clinical Trials), an F-CRIN network, INSERM U-1148, Paris, France
- bNLHI, ICMS, Royal Brompton Hospital, Imperial College, London, United Kingdom
- cColumbia University Medical Center and the Cardiovascular Research Foundation, New York, New York
- dStanford Center for Clinical Research (SCCR); Department of Medicine; Stanford School of Medicine, Stanford, California
- eBeth Israel Deaconess Medical Center, Division of Cardiology, Harvard Medical School, Boston, Massachusetts
- fKerckhoff Heart and Thorax Center, Bad Nauheim, Germany
- gScripps Clinic and Scripps Translational Science Institute, La Jolla, California
- hThe Medicines Company, Parsippany, New Jersey
- iUniversity of Auckland, Auckland City Hospital, Auckland, New Zealand
- jBrigham and Women’s Hospital Heart & Vascular Center and Harvard Medical School, Boston, Massachusetts
- ↵∗Reprint requests and correspondence:
Dr. Ph. Gabriel Steg, Hôpital Bichat, 46 rue Henri Huchard, 75018 Paris, France.
Objectives The purpose of this study was to examine the safety and efficacy of cangrelor in patients with stable angina (SA) or acute coronary syndrome (ACS).
Background The CHAMPION PHOENIX (A Clinical Trial Comparing Cangrelor to Clopidogrel Standard Therapy in Subjects Who Require Percutaneous Coronary Intervention) trial demonstrated that cangrelor significantly reduced periprocedural ischemic events in all-comer percutaneous coronary intervention with a modest increase in mild and moderate bleeding. Whether this benefit is consistent across SA and ACS has not been explored fully.
Methods The CHAMPION PHOENIX trial compared periprocedural administration of cangrelor or clopidogrel, with either a 300- or 600-mg loading dose for the prevention of periprocedural complications in patients undergoing percutaneous coronary intervention. Among the 10,942 patients in the modified intention to treat population, 6,358 patients were classified as having SA, and 4,584 patients had ACS (including unstable angina, non ST-segment elevation myocardial infarction and ST-segment elevation myocardial infarction) at randomization. The primary composite endpoint was death, myocardial infarction, ischemia-driven revascularization, or stent thrombosis at 48 h. A key secondary endpoint was stent thrombosis, and the primary safety endpoint was GUSTO (Global Utilization of Streptokinase and Tissue Plasminogen Activator for Occluded Coronary Arteries) severe bleeding.
Results Cangrelor consistently reduced the primary endpoint in SA and ACS (odds ratio [OR]: 0.83 [95% confidence interval (CI): 0.67 to 1.01] and OR: 0.71 [95% CI: 0.52 to 0.96], respectively; interaction p = 0.41). Cangrelor also consistently reduced stent thrombosis in SA and ACS (OR: 0.55 [95% CI: 0.30 to 1.01] and OR: 0.67 [95% CI: 0.42 to 1.06], respectively; interaction p = 0.62). The impact of cangrelor on GUSTO severe/moderate bleeding was also similar for SA and ACS (OR: 1.49 [95% CI: 0.67 to 3.33] and OR: 1.79 [95% CI: 0.79 to 4.07], respectively; interaction p = 0.75).
Conclusions The benefits and risks of cangrelor were consistent in patients with SA and ACS. (A Clinical Trial Comparing Cangrelor to Clopidogrel Standard Therapy in Subjects Who Require Percutaneous Coronary Intervention [PCI] [CHAMPION PHOENIX] [CHAMPION]; NCT01156571)
Antiplatelet therapy combining aspirin and P2Y12 inhibition is a necessary adjunct to percutaneous coronary intervention (PCI) for acute coronary syndrome (ACS) or stable angina (SA) to avoid both periprocedural and long term thrombotic complications after stent implantation (1–3). Newer generation oral P2Y12 antiplatelet agents have been developed to overcome the limitations of clopidogrel, namely, its modest and variable antiplatelet effect, and slow onset and offset (1–5). However, several limitations remain with oral agents in this setting, particularly when the need for platelet inhibition is urgent or desired at the time of PCI such as complex angioplasty (6) or when oral administration can be problematic or ineffective, such as in ST-segment elevation myocardial infarction (STEMI), where nausea and/or vomiting and morphine administration impair absorption, or in cardiac arrest (7,8).
Cangrelor is a new, intravenous, direct, potent, and reversible P2Y12 inhibitor with immediate (within 2 min) onset and rapid offset (half-life of 3 to 6 min and return of platelet function to baseline within 1 h). The CHAMPION PHOENIX (A Clinical Trial Comparing Cangrelor to Clopidogrel Standard Therapy in Subjects Who Require Percutaneous Coronary Intervention) trial demonstrated a significant reduction of periprocedural ischemic events without a significant increase in GUSTO (Global Utilization of Streptokinase and Tissue Plasminogen Activator for Occluded Coronary Arteries) severe bleeding or in transfusions (9). These results have been further supported by a patient-level meta-analysis of all phase III trials of cangrelor in the setting of PCI (1,2,9–12).
Because the periprocedural risk of PCI differs widely according to the indication (i.e., ACS or SA) (4,5,13–15), the benefits and risks of cangrelor may vary accordingly.
We examined whether the treatment effect of cangrelor was consistent, irrespective of clinical presentation and, specifically, whether the risks and benefits were similar for patients with SA or with ACS.
The design of the CHAMPION PHOENIX trial (7,8,16) and the results of the primary trial have been published previously (9). In brief, 11,145 patients undergoing either urgent or elective PCI and receiving guideline-recommended therapy were randomized to receive either cangrelor bolus and infusion or placebo bolus and infusion, and an oral loading dose of clopidogrel (600 or 300 mg at the discretion of the physician) or a matching placebo at the time of PCI (either at the start or at the end, at the discretion of the physician) in a double-blind double-dummy placebo-controlled trial. Patient designation as SA or ACS was based on site declaration at the time of interactive voice response system randomization.
The study population consisted of males or nonpregnant females ≥18 years of age who required PCI for SA, non–ST-segment elevation ACS (NSTE-ACS) or STEMI. Patients provided written informed consent. Major exclusion criteria were receipt of any of the following before randomization: P2Y12 inhibitor at any time within 7 days, eptifibatide or tirofiban use within 12 h, abciximab use within 7 days, or fibrinolytic therapy within 12 h.
Patients were randomized to either cangrelor or clopidogrel after angiography before PCI in a double-dummy, double-blind manner via interactive voice response system. Randomization was stratified by site, baseline status (normal or abnormal, as defined by a combination of biomarkers, electrocardiographic changes, and symptoms), and intended clopidogrel loading dose (600 or 300 mg). The dose of cangrelor used was a 30 μg/kg bolus and a 4 μg/kg/min infusion for ≥2 h or the duration of the procedure, whichever was longer. After randomization, patients received a bolus plus infusion of cangrelor or matching placebo, and with timing either at the start or the end of the procedure as directed by the site investigator, the first set of capsules containing either 600 or 300 mg clopidogrel or matching placebo. At the end of the infusion, patients received a second set of capsules containing either clopidogrel or matching placebo. Aspirin 75 to 325 mg maintenance dose and clopidogrel 75 mg (or other P2Y12 inhibitor) maintenance dose were at the investigator’s discretion per local guidelines, as was the choice of periprocedural anticoagulant (unfractionated heparin, bivalirudin, low-molecular-weight heparin, or fondaparinux). Glycoprotein IIb/IIIa inhibitors were allowed only as bailout therapy during PCI for new or persistent thrombus formation, slow or no reflow, side branch compromise, dissection, or distal embolization. Arterial access and sheath management was left to the discretion of the investigator.
The primary efficacy endpoint was all-cause death, myocardial infarction (MI), ischemia-driven revascularization (IDR), or stent thrombosis at 48 h after randomization; the key secondary endpoint was stent thrombosis at 48 h. The key safety endpoint was GUSTO severe bleeding at 48 h. Because this rate was very low, GUSTO severe and moderate bleeding rates were combined to provide a larger number of events to examine potential subgroup interaction. The modified intent-to-treat population (patients who actually received PCI and study drug) was used for all efficacy analyses. Death, MI, IDR, and stent thrombosis were adjudicated by the Duke Clinical Research Institute Clinical Events Committee for events occurring during the first 30 days after randomization. The Clinical Events Committee definitions for MI are presented in the original manuscript (9). Briefly, in these definitions based on second universal definition of MI (16,17), MI was defined as elevation ≥3 fold upper limit of normal of cardiac biomarkers after PCI (creatine kinase myocardial band or troponin) in case of normal baseline status. For patients with an elevated baseline biomarker (troponin), the protocol required a minimum of 2 baseline biomarker samples ≥6 h apart and measurements of all samples were controlled by a central core laboratory. Criteria for periprocedural MI within 48 h was based on baseline biomarker status. If baseline biomarkers were abnormal but decreasing, then any 1 of 3 clinical criteria (angiographic complication, or ischemic symptoms, or new electrocardiographic changes, plus re-elevation of creatine kinase myocardial band to ≥3 times the upper limit of normal and ≥50% from the nadir previous value were required. However, if baseline biomarkers were abnormal but increasing, then both an angiographic complication and new electrocardiographic changes, plus re-elevation of creatine kinase myocardial band ≥3 times the upper limit of normal and ≥50% from the nadir previous value were required. For this analysis, TIMI (Thrombolysis In Myocardial Infarction) scale and ACUITY (Acute Catheterization and Urgent Intervention Triage strategY) scale bleeding definitions were also applied. Bleeding endpoints were not adjudicated (18).
For the overall CHAMPION PHOENIX trial, the composite event rate was assumed to be 5.1% in the clopidogrel group and 3.9% in the cangrelor group (a 24.5% reduction in the odds ratio [OR], based on prior studies), resulting in a sample size of approximately 10,900 patients to provide 85% power. A 2-sided overall alpha of 0.05 was used for all analyses. Although the SA and ACS subgroups were prespecified, they were not powered for formal superiority or noninferiority analyses.
Continuous variables are summarized as median values and quartiles or as mean ± SD, as appropriate, and were compared using the Student t test or Wilcoxon rank-sum test accordingly. Categorical variables were presented as rate (%) and compared by the chi-square or Fisher’s exact test as appropriate. Interaction between the treatment and different subgroups on endpoint events was tested using logistic regression. No adjustment was made for multiple comparisons. The numbers (%) of patients within each subpopulation (SA, ACS) were summarized by treatment group. The primary efficacy analysis was conducted on the composite incidence rate of Clinical Events Committee–adjudicated all-cause mortality, MI, IDR, or stent thrombosis in the 48 h after randomization. All summaries and statistical analyses were performed using SAS version 9.3 (SAS Institute, Inc., Cary, North Carolina).
Of the 10,942 patients included in the modified intent-to-treat population, 6,358 (58.1%) were identified by site investigators as SA and 4584 (41.9%) as ACS. In the overall CHAMPION PHOENIX population, the average age was 64 years, 28% were female, and the median time from angiography to PCI was 28 min (25th to 75th percentile: 19 to 44 min). Demographic characteristics and other baseline factors for SA and ACS groups are presented in Table 1. There were major differences between groups in terms of baseline characteristics. In particular, ACS patients were younger, more frequently male, smokers, and had less previous history of MI, peripheral artery disease, heart failure, diabetes, previous PCI, or coronary artery bypass grafting than patients with SA. Procedural characteristics are presented in Table 2. Again, there were important differences in procedural characteristics between the groups. ACS patients more frequently underwent femoral access and had received clopidogrel on or before the start of PCI, more frequently had multivessel disease, less frequently received a drug-eluting stent than patients with SA.
The incidence of the primary composite efficacy endpoint in the SA subset was 5.7% and 6.8%, for cangrelor and clopidogrel patients, respectively; rates in the ACS subset were 3.3% and 4.6%, respectively. Components of the primary endpoint and other composite endpoints are presented in Figure 1. Overall, event rates were higher among SA than among ACS patients, and this was driven entirely by a much higher incidence of periprocedural MI (which was defined differently in ACS and non-ACS patients), whereas the rates of death and of ST were higher among ACS patients.
Cangrelor consistently reduced the 48-h primary composite endpoint of all-cause death, MI, IDR, or stent thrombosis in patients presenting for PCI with SA (OR: 0.83; 95% confidence interval [CI]: 0.67 to 1.01; p = 0.06) and in patients presenting with ACS (OR: 0.71; 95% CI: 0.52 to 0.96; p = 0.02; interaction p value = 0.41). A similar consistent effect of cangrelor in reducing the primary 48-h composite endpoint in patients presenting for PCI with SA or with ACS, was observed when the SCAI definition rather than the second universal MI definition was used to define periprocedural MI (Online Appendix).
Likewise, the key secondary efficacy endpoint of stent thrombosis was also consistently lower at 48 h with cangrelor in the SA (OR: 0.55; 95% CI: 0.30 to 1.01; p = 0.05) and ACS subgroups (OR: 0.67; 95% CI: 0.42 to 1.06; p = 0.09; interaction p = 0.62). In the SA subset, the incidence of stent thrombosis was 0.5% and 0.9% in the cangrelor and clopidogrel groups, respectively, whereas in ACS patients the corresponding rates were 1.3% and 2.0%, respectively (Figure 1).
The rate of GUSTO severe bleeding was very low overall; likewise, the rate of GUSTO severe or moderate bleeding was low and similar between treatment groups in the SA (0.5% for cangrelor vs. 0.3% for clopidogrel [OR: 1.49; 95% CI: 0.67 to 3.33]) and ACS subgroups (0.7% for cangrelor vs. 0.4% for clopidogrel [OR: 1.79; 95% CI: 0.79 to 4.07; interaction p = 0.75]). Importantly, there was no interaction between SA and ACS groups for bleeding with respect to the comparison of cangrelor and clopidogrel. When any GUSTO bleeding was measured, there was a consistent and similar increase with cangrelor for both SA and ACS patients (interaction p = 0.65). Bleeding rates as defined by TIMI criteria were also low, similar between SA and ACS subgroups and by treatment group. In addition, bleeding measured using the more sensitive ACUITY criteria was consistently increased with cangrelor relative to clopidogrel in both stable and ACS patients. Finally, the rate of transfusion did not differ between the SA (OR: 1.49; 95% CI: 0.61 to 3.66) and ACS (OR: 1.64; 95% CI: 0.68 to 3.96) subgroups (interaction p = 0.88) (Figure 2).
In a post hoc analysis, the primary efficacy and primary safety endpoints were combined to provide a composite net adverse clinical events endpoint (Figure 3). Cangrelor consistently reduced net adverse clinical events compared with clopidogrel overall (4.8% vs. 6.0%; OR: 0.80; 95% CI: 0.67 to 0.94; p = 0.008), as previously reported (9), but also in both SA and ACS subsets (OR: 0.82 [95% CI: 0.67 to 1.01] and OR: 0.74 [95% CI: 0.55 to 1.00], for SA and ACS respectively; interaction p = 0.56).
At 30 days, the reduction with cangrelor in the composite endpoint of death, MI, IDR, or stent thrombosis in the overall population (6.0% vs. 7.0%; OR: 0.85; 95% CI: 0.73 to 0.99; p = 0.03) was maintained with no interaction for patients presenting with SA or for ACS, respectively (OR: 0.83 [95% CI: 0.68 to 1.00], OR: 0.88 [95% CI: 0.69 to 1.13]; interaction p = 0.68).
Cangrelor also reduced stent thrombosis at 30 days consistently for both patients with SA (OR: 0.53; [95% CI: 0.32 to 0.88]) and for ACS patients (OR: 0.79; [95% CI: 0.54 to 1.15]; interaction p = 0.22).
Cangrelor as compared with clopidogrel given at the time of PCI consistently reduced the risk of periprocedural ischemic events in both ACS and SA patients. These results are mostly driven by a decrease in periprocedural MI, but the key secondary endpoint of ST was also reduced in both groups. It may be counterintuitive that the ischemic event rate, and, specifically, the incidence of the primary composite outcome, was higher among SA than ACS patients. However, the higher rate of periprocedural MI in SA patients relative to ACS patients reflects the difficulties in ascertaining periprocedural MI in patients presenting with an ongoing MI and the use of selective criteria that required additional evidence of MI in the setting of ACS in CHAMPION PHOENIX (9). Because the diagnosis of PCI-related MI includes an increase in biomarkers, when biomarkers are already increased at baseline, it is difficult to detect whether a new increase is related to complications of the PCI procedure; it is more straightforward to diagnose periprocedural MI in patients with normal biomarkers before PCI (the SA subset) (19).
Bleeding rates were low in both treatment arms. The effects of cangrelor on bleeding events were consistent for SA and ACS patients: there was no increase in the primary safety endpoint of GUSTO severe bleeding, or in the combined GUSTO severe to moderate bleeding, nor was there a difference in TIMI major bleeding or in the need for transfusion. However, there was increased bleeding with cangrelor when more sensitive measures (such as any GUSTO bleeding or ACUITY major bleeding) were used, and the increase was consistent across both subsets. Post hoc analyses of net adverse clinical events, defined either using the composite of death, MI, IDR, stent thrombosis, or GUSTO severe bleeding or the more sensitive composite of death, MI, IDR, stent thrombosis, or GUSTO severe or moderate bleeding, found a consistent advantage with cangrelor. Therefore, cangrelor seemed to have a favorable benefit–risk profile in both groups at 48 h and at 30 days.
Both STEMI and NSTE-ACS international guidelines traditionally recommended initiation of dual oral antiplatelet therapy as soon as possible in ACS (20,21). However, in NSTE-ACS, many clinicians particularly in the United States, are reluctant to load patients early, before angiography has been performed and a decision to proceed to PCI has been made, largely because of the fear of having to delay cardiac bypass surgery for ≥5 days for clopidogrel and 7 days for prasugrel (as recommended by guidelines and the drug labeling to minimize the risk of perioperative bleeding). The ACCOAST (A Comparison of Prasugrel at PCI or Time of Diagnosis of Non-ST Elevation Myocardial Infarction) trial (22) has questioned the need for prehospital and early hospital treatment with prasugrel in NSTE-ACS, because it showed a clear increase in bleeding risk but no decrease in ischemic outcomes when prasugrel was initiated upstream of coronary angiography compared with at the time of angiography. This has resulted in a revision of the guidelines regarding the need for early pre-treatment with P2Y12 antagonists in non–ST-segment ACS (23,24). It is uncertain whether the findings of the ACCOAST trial apply to ticagrelor, given that, in the PLATO (Study of PLATelet Inhibition and Patient Outcomes) trial, patients were initiated with ticagrelor or clopidogrel at the time of randomization and ticagrelor showed clear benefit. This has generated substantial debate on the value of pre-treatment in NSTE-ACS (24,25). Yet, whenever clinicians are reluctant to start oral P2Y12 inhibitors before angiography, cangrelor provides an alternative option, allowing immediate antiplatelet efficacy at the time of PCI to minimize thrombotic periprocedural complications. In addition, given the rapid offset, use of cangrelor rather than oral agent preloading would facilitate same day or next day surgery in the subgroup of ACS patients that require coronary artery bypass grafting surgery, which can reach up to 10% of ACS (26).
In STEMI, the oral P2Y12 agents have well-documented limitations, related to difficulties of oral administration, impaired absorption, slow onset of action, interaction with morphine, and ultimately delayed and possibly reduced efficacy (27). In contrast, the probability of the patient requiring urgent surgery is low. In the ATLANTIC (A 30 Day International, Randomized, Parallel-group, Double-blind, Placebo-controlled Phase IV Study to Evaluate Efficacy and Safety of Pre-hospital vs. In-hospital Initiation of Ticagrelor Therapy in STEMI Patients Planned for PCI) trial, treatment with oral P2Y12 blockers with ticagrelor was given either in the prehospital setting or at the time of primary PCI. There was no difference in the 2 coprimary outcomes of ST-segment resolution and infarct artery TIMI flow, although the secondary outcome of acute ST was reduced with prehospital treatment with ticagrelor (28).
Finally, in stable coronary artery disease, the only P2Y12 blocker currently indicated for patients undergoing elective PCI is clopidogrel, which requires several hours to reach full efficacy. Because of this delay, physicians are faced with a conundrum when they consider ad hoc PCI immediately after coronary angiography: to either preload patients with oral clopidogrel several hours before coronary angiography, with the risk of unnecessary treatment in those who will not go on to PCI (and the attendant bleeding risks, particularly if these patients will need surgery), or delay oral loading until angiography has been performed and a decision to proceed to PCI has been made, in which case the intervention would proceed with suboptimal antiplatelet coverage or with postponement of the PCI.
Regardless of the setting, primary PCI for STEMI, NSTE-ACS, or elective PCI for SA, cangrelor provides added flexibility to clinicians by ensuring an immediate, consistent, and reversible antiplatelet effect and obviating the need to commit to pre-treatment. CHAMPION PHOENIX (9) demonstrated that cangrelor could significantly reduce periprocedural ischemic events, an observation that was confirmed in a patient-level pooled analysis of all 3 CHAMPION trials (12), although the 2 previous trials (CHAMPION PCI and CHAMPION PLATFORM) did not reach their primary outcome (10,11). However, the periprocedural risk of PCI differs widely between the stable and the unstable (13–15,29–32) situation, with an increased risk of both stent thrombosis and bleeding events in ACS patients. The current analysis demonstrated consistent benefits of cangrelor in every individual ischemic endpoint for both the SA and ACS groups. Specifically relating to stent thrombosis, it is important to note that the CHAMPION PHOENIX definition included both Academic Research Consortium-defined events (18), but also intraprocedural stent thromboses assessed by a blinded angiographic core lab that have been previously reported to have detrimental prognostic impact (33). The reductions in this enriched stent thrombosis endpoint by cangrelor were again consistent in both SA and ACS subgroups.
First, these are subset analyses and should, therefore, be interpreted with caution, because they are by definition underpowered compared with the overall trial results. Second, ascertainment of periprocedural MI is difficult in ACS patients and, therefore, periprocedural MI is likely underestimated in this population despite a careful blinded event adjudication process, although this would have been expected to underestimate any benefit of cangrelor. Finally, CHAMPION PHOENIX compared cangrelor with clopidogrel, given at the time of PCI (either at the onset or at the end of the procedure); therefore, it does not provide information on the relative efficacy and safety if cangrelor had been compared with prasugrel or ticagrelor for ACS or with several hours of clopidogrel pre-treatment in SA. Importantly, clopidogrel remains the only approved oral P2Y12 inhibitor for patients undergoing elective PCI for SA, and remains widely used among ACS patients (33).
In CHAMPION PHOENIX, periprocedural treatment with cangrelor reduced ischemic complications both in patients presenting with SA or ACS and requiring PCI without increasing GUSTO severe bleeding or transfusions. This suggests that, despite differing patient characteristics and risks of ischemic and bleeding events, cangrelor provides a consistent efficacy and safety profile across the spectrum of patients undergoing PCI.
WHAT IS KNOWN? Cangrelor is more efficient and safe than clopidogrel as periprocedural treatment for PCI for both stable and unstable patients.
WHAT IS NEW? Routine use of cangrelor reduces periprocedural complications of PCI in P2Y12, inhibitor-naive patients.
WHAT IS NEXT? Ascertainment of periprocedural MI is difficult in ACS patients and its incidence may be underestimated. Further refinement of adjudication methods may limit this underestimation.
The authors thank Steven E. Elkin, MS, and Debra Bernstein, PhD, of The Medicines Company for their statistical support, along with Yuyin Liu, MS, and Lanyu Lei, MS, of the Harvard Clinical Research Institute for their independent verification of the analyses. Harvard Clinical Research Institute received funding from The Medicines Company for these analyses.
For supplemental material, please see the online version of this article.
↵∗ A full list of investigators can be found in Bhatt et al. N Engl J Med 2013;368:1303-13.
The CHAMPION PHOENIX trial was funded by The Medicines Company.
Dr. Steg has received a research grant (to INSERM U1148) from Sanofi, and Servier; speaking or consulting fees from Amarin, AstraZeneca, Bayer, Boehringer-Ingelheim, Bristol-Myers Squibb, CSL-Behring, Daiichi-Sankyo, GlaxoSmithKline, Janssen, Lilly, Merck, Novartis, Pfizer, Regeneron, Roche, Sanofi, Servier, The Medicines Company; and owns stocks from Aterovax. Dr. Mahaffey’s financial disclosures before August 1, 2013, can be viewed at www.dcri.org/about-us/conflict-of-interest/Mahaffey-COI_2011-2013.pdf; disclosures after August 1, 2013, can be viewed at http://med.stanford.edu/profiles/kenneth-mahaffey. Dr. Gibson has received modest consulting fees from The Medicines Company. Dr. Hamm has received honoraria from Abbott, AstraZeneca, Bayer, Boehringer Ingelheim, Daiichi Sankyo, Sanofi, Pfizer and The Medicines Company. Dr. Price has received consulting and speaker honoraria from The Medicines Company and AstraZeneca; and consulting honoraria from Merck, Boehringer Ingleheim, Terumo, Boston Scientific, Medtronic, and St. Jude Medical. Drs. and Deliargyris are full-time employees of The Medicines Company. Dr. White has received honoraria from AstraZeneca; and research funding from Sanofi, Eli Lilly, National Health Institute, GlaxoSmithKline, Merck Sharpe & Dohme, and AstraZeneca. Dr. Harrington has received research grants/contracts from National Heart Lung and Blood Institute, Duke, AstraZeneca, CSL-Behring, GlaxoSmithKline, Merck, Portola, Regado, Bristol-Myers Squibb/Pfizer, Janssen, Sanofi, and The Medicines Company; and consulting/advisory fees from Adverse Events, Amgen, Element Science, Gilead, Merck, MyoKardia, The Medicines Company, VidaHealth and WebMD. Dr. Bhatt is on the advisory board for Cardax, Elsevier Practice Update Cardiology, Medscape Cardiology, and Regado Biosciences; is on the Board of Directors for Boston VA Research Institute and the Society of Cardiovascular Patient Care; is Chair of the American Heart Association Get With The Guidelines Steering Committee; is on the Data Monitoring Committees for Duke Clinical Research Institute, Harvard Clinical Research Institute, Mayo Clinic, and Population Health Research Institute; has received honoraria from American College of Cardiology (Senior Associate Editor, Clinical Trials and News, ACC.org), Belvoir Publications (Editor in Chief, Harvard Heart Letter), Duke Clinical Research Institute (clinical trial steering committees), Harvard Clinical Research Institute (clinical trial steering committee), HMP Communications (Editor in Chief, Journal of Invasive Cardiology), Journal of the American College of Cardiology (Guest Editor; Associate Editor), Population Health Research Institute (clinical trial steering committee), Slack Publications (Chief Medical Editor, Cardiology Today’s Intervention), WebMD (CME steering committees), Clinical Cardiology (Deputy Editor); has received research funding from Amarin, AstraZeneca, Bristol-Myers Squibb, Eisai, Ethicon, Forest Laboratories, Ischemix, Medtronic, Pfizer, Roche, Sanofi, and The Medicines Company (including for his role as Co-Chair of CHAMPION PHOENIX); is Site Co-Investigator for Biotronik and St. Jude Medical; is a Trustee for American College of Cardiology; and has unfunded research for FlowCo, PLx Pharma, and Takeda.
- Abbreviations and Acronyms
- acute coronary syndrome(s)
- confidence interval
- ischemia-driven revascularization
- myocardial infarction
- NSTE ACS
- non–ST-segment elevation acute coronary syndrome
- odds ratio
- percutaneous coronary intervention
- stable angina
- ST-segment elevation myocardial infarction
- Received June 10, 2016.
- Accepted June 19, 2016.
- American College of Cardiology Foundation
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