Author + information
- Received August 5, 2015
- Accepted August 13, 2015
- Published online December 21, 2015.
- Larry R. Jackson II, MD∗∗ (, )
- Christine Ju, MS∗,
- Marjorie Zettler, PhD, MPH†,
- John C. Messenger, MD‡,
- David J. Cohen, MD§,
- Gregg W. Stone, MD‖,
- Brian A. Baker, PharmD¶,
- Mark Effron, MD†,
- Eric D. Peterson, MD, MPH∗ and
- Tracy Y. Wang, MD, MHS, MSc∗
- ∗Duke Clinical Research Institute, Duke University School of Medicine, Durham, North Carolina
- †Lilly USA, LLC, Indianapolis, Indiana
- ‡University of Colorado School of Medicine, Aurora, Colorado
- §Saint Luke’s Mid America Heart Institute, University of Missouri-Kansas City School of Medicine, Kansas City, Missouri
- ‖Columbia University College of Physicians and Surgeons, New York, New York
- ¶Daiichi-Sankyo, Inc., Parsippany, New Jersey
- ↵∗Reprint requests and correspondence:
Dr. Larry R. Jackson II, Duke University Medical Center, Duke Clinical Research Institute, 2400 Pratt Street, Suite 7009, Durham, North Carolina 27705.
Objectives The purpose of this study was to determine whether bleeding risk varies depending on which P2Y12 receptor inhibitor agent is used.
Background Prior studies have shown significant bleeding risk among patients treated with triple therapy (i.e., oral anticoagulant, P2Y12 receptor inhibitor, and aspirin).
Methods We evaluated patients with acute myocardial infarction (MI) treated with percutaneous coronary intervention (PCI) at 233 hospitals in the United States enrolled in the TRANSLATE-ACS (Treatment with Adenosine Diphosphate Receptor Inhibitors: Longitudinal Assessment of Treatment Patterns and Events After Acute Coronary Syndrome) study (April 2010 to October 2012). Using inverse probability-weighted propensity modeling, we compared 6-month adjusted risks of Bleeding Academic Research Consortium (BARC) bleeding, stratifying by whether or not bleeding was associated with rehospitalization among patients discharged on aspirin + anticoagulant + clopidogrel (triple-C), aspirin + anticoagulant + prasugrel (triple-P), aspirin + clopidogrel (dual-C), or aspirin + prasugrel (dual-P).
Results Of 11,756 MI patients, 526 (4.5%) were discharged on triple-C, 91 (0.8%) on triple-P, 7,715 (66%) on dual-C, and 3,424 (29%) on dual-P. Compared with dual-therapy patients, triple-therapy patients had significantly higher any BARC-defined bleeding. Triple-P was associated with a greater risk of any BARC-defined bleeding events compared with triple-C. This finding was driven mostly by an increased risk of bleeding events that were patient-reported only and did not require rehospitalization. There were no significant differences in bleeding requiring rehospitalization between the triple-P and -C groups.
Conclusions Among MI patients, the addition of an oral anticoagulant was associated with a significantly greater risk of any BARC-defined bleeding relative to dual antiplatelet therapy, regardless of which P2Y12 receptor inhibitor was selected. Among patients on triple therapy, prasugrel use was associated with higher patient-reported–only bleeding, but not bleeding requiring rehospitalization, than clopidogrel-treated patients.
Dual antiplatelet therapy (DAPT) with aspirin and a P2Y12 receptor inhibitor is standard of care following percutaneous coronary intervention (PCI) for patients with acute myocardial infarction (MI). However, approximately 5% to 10% of patients who have acute MIs have conditions, such as atrial fibrillation or prosthetic valves, for which oral anticoagulants provide superior benefit when compared with antiplatelet agents (1,2). Patients with an indication for anticoagulant therapy on top of DAPT represent a clinical conundrum, given the lack of rigorous evidence supporting net clinical benefit with triple therapy use (3–5).
Previous studies of triple therapy have primarily focused on clopidogrel, which has been the most widely studied P2Y12 receptor inhibitor (6,7). Nevertheless, novel and more potent antiplatelet agents, like prasugrel, are now in clinical use for patients with acute MI treated with PCI (8,9). To date, there is limited information on the relative effectiveness and safety of clopidogrel versus prasugrel among patients requiring triple therapy. The TRANSLATE-ACS (Treatment with Adenosine Diphosphate Receptor Inhibitors: Longitudinal Assessment of Treatment Patterns and Events After Acute Coronary Syndrome) study is a prospective, longitudinal, observational study of patients in the United States who had either ST-segment elevation myocardial infarction (STEMI) or non-STEMI treated with PCI and a P2Y12 receptor inhibitor during their index hospitalization. This analysis of the TRANSLATE-ACS study population was designed to address the following aims: 1) describe the prevalence of triple therapy use with clopidogrel versus prasugrel at discharge; 2) compare clinical characteristics and outcomes between patients receiving triple therapy versus DAPT; and 3) compare clinical characteristics and outcomes between patients receiving triple therapy with clopidogrel versus prasugrel.
The TRANSLATE-ACS study design has been previously described (10). Briefly, STEMI and non-STEMI patients treated with PCI and a P2Y12 receptor inhibitor during the index MI hospitalization were included. Patients who were unable to provide written informed consent for longitudinal follow-up were excluded. Because the main intent of the study was to observe longitudinal antiplatelet therapy use in routine clinical practice, patients who were participating in another research study that specified use of either an investigational or approved P2Y12 receptor inhibitor within the first 12 months post-MI were excluded (10). As TRANSLATE-ACS was an observational study, all treatment decisions were left to the discretion of the individual treating physicians in accordance with practice guideline recommendations and local standards of care. The TRANSLATE-ACS study received approval from the Duke University Institutional Review Board, as well as the institutional review boards of all participating sites. All subjects provided written informed consent.
Between April 2010 and October 2012, 12,365 acute MI patients treated at 233 hospitals in the United States with PCI were enrolled in the TRANSLATE-ACS study. For the purpose of this analysis, we considered only patients who were discharged on DAPT (aspirin plus either clopidogrel or prasugrel) or triple therapy (DAPT plus any of the following oral anticoagulants approved for clinical use during the study period: warfarin, dabigatran, or rivaroxaban). We excluded patients who died in-hospital, patients discharged on other antiplatelet or anticoagulant combinations, and patients discharged on none of these medications (Figure 1). Our final study population included 11,756 acute MI patients discharged from 233 U.S. hospitals.
Data collection and study endpoints
Baseline clinical characteristics, demographics, past medical history, in-hospital antiplatelet therapy or antithrombotic therapy use, laboratory studies, PCI data, and discharge medications were abstracted from the medical record or patient interviews into the TRANSLATE-ACS data collection form using standardized data elements and definitions (10). Data were screened upon entry, and only those meeting pre-determined criteria for completeness and accuracy were entered into the database for analysis.
Post-discharge study follow-up was conducted via centralized telephone interviews by trained personnel at the Duke Clinical Research Institute (Durham, North Carolina) at 6 weeks and 6, 12, and 15 months. The primary outcomes of this analysis were post-discharge bleeding and major adverse cardiovascular events (MACE) during the 6-month follow-up period after the index MI hospitalization. In this analysis, bleeding was defined using Bleeding Academic Research Consortium (BARC) criteria (11). Bleeding events involving a rehospitalization (at least an overnight stay regardless of inpatient admission, observation, or emergency department stay only status) were independently validated by study physicians at the Duke Clinical Research Institute on the basis of review of medical records and classified as BARC bleeding types 2 through 5. Bleeding events involving rehospitalization were also classified using the GUSTO (Global Use of Strategies to Open Occluded Arteries) criteria; moderate/severe bleeding was defined as intracranial hemorrhage, bleeding that caused hemodynamic compromise requiring intervention, or bleeding that required blood transfusion (12). Patient-reported–only bleeding events that did not necessarily involve an overnight in-hospital stay were collected during follow-up telephone interviews with the question: “Since your discharge from the hospital on (insert discharge date) or last interview on (insert date), have you experienced any severe unexplained bruising or any bleeding?” Patient-reported–only bleeding events were classified as BARC type 1 or 2 depending on whether the bleeding prompted the patient to seek clinical evaluation (BARC type 1 bleeding is defined as bleeding that is not actionable and does not cause the patient to seek unscheduled performance of studies, hospitalization, or treatment by a health care professional). MACE were defined as a composite of death, MI, unplanned revascularization, or stroke at 6 months; all MACE events were independently adjudicated by study physicians via review of relevant medical records using protocol-specified endpoint definitions (10).
Patients were divided into 1 of the following 4 groups according to the specific antiplatelet and anticoagulant medications prescribed at discharge: 1) triple therapy with clopidogrel (triple-C: aspirin + anticoagulant + clopidogrel); 2) triple therapy with prasugrel (triple-P: aspirin + anticoagulant + prasugrel); 3) DAPT with clopidogrel (dual-C: aspirin + clopidogrel); and 4) DAPT with prasugrel (dual-P: aspirin + prasugrel). We compared baseline and in-hospital characteristics between these groups. Categorical variables were summarized by counts and percentages and compared using the Pearson chi-square test or Fisher exact test. Continuous variables were summarized by median, 25th and 75th percentiles, and compared using Kruskal-Wallis tests. Poisson regression models, with generalized estimating equations to account for within hospital clustering using inverse probability-weighted propensity score adjustment, were performed to compare any BARC bleeding between treatment groups. Additionally, logistic models with generalized estimating equations, again using inverse probability-weighted propensity score adjustment, were conducted to examine BARC bleeding as an ordinal outcome (involved rehospitalization vs. patient-reported–only vs. no bleeding). Inverse probability-weighted adjusted Cox proportional hazard modeling was used to compare risks of GUSTO moderate/severe bleeding and MACE. Follow-up began at the date of discharge and was censored at the first BARC bleeding event date (if known) or the date of the interview during which the event was reported, the death date, or the 6-month interview date. Propensity score models were created for each of the following comparisons: 1) triple-C versus dual-C; 2) triple-P versus dual-P; and 3) triple-C versus triple-P (C statistics: triple-P vs. triple-C [0.725]; triple-P vs. dual-P [0.834]; triple-C vs. dual-C [0.835]) (Online Tables 1 to 3). Covariate selection was based on previous risk models, significant univariable comparison results, and clinical judgment. Pre- and post-inverse probability-weighted balance of all covariates between the different exposures was assessed using Cramer’s Phi for categorical variables and R-squared for continuous variables (Online Appendix, Online Figures 1 and 2). For the comparison of triple-C versus triple-P, modeling was performed on the subset of 327 patients (n = 77 for prasugrel and n = 250 for clopidogrel) who had overlapping propensity scores (Online Figure 3). All statistical analyses were performed at the Duke Clinical Research Institute using SAS software (version 9.3, SAS Institute, Cary, North Carolina).
Patient and baseline characteristics
Among the 11,756 acute MI patients treated with PCI, 617 patients (5%) were discharged on triple therapy (Figure 1). Triple therapy with clopidogrel (triple-C) was used in 526 patients, whereas triple therapy with prasugrel (triple-P) was used in 91 (4.5% and 0.8% of the overall study population, respectively). Among patients discharged on triple therapy, warfarin was the predominant oral anticoagulant used in 572 patients (93%), whereas novel oral anticoagulants (dabigatran or rivaroxaban) were used in 45 patients. Among patients discharged on DAPT alone, 7,715 (66% of the overall study population) were treated with clopidogrel (dual-C) and 3,424 (29%) received prasugrel (dual-P).
Prior to admission, 347 (3%) patients were on home oral anticoagulant therapy. The indications for anticoagulation were: prosthetic valve (n = 26, 7%), venous thromboembolism (n = 69, 20%), atrial fibrillation/atrial flutter (n = 200, 58%), other (n = 48, 14%), and missing (n = 4, 1%). Among patients on home anticoagulant therapy prior to admission, 215 (62%) were discharged on triple-C, 16 (5%) were discharged on triple-P, 104 (30%) were discharged on dual-C, and 12 (3%) were discharged on dual-P. Overall, 231 of the 617 (37%) patients were discharged on triple therapy, and 116 of the 11,139 (1.0%) patients discharged on DAPT only were taking an oral anticoagulant prior to admission.
Baseline characteristics of the study cohort are shown according to discharge treatment group in Table 1. Dual-C patients were younger than those treated with triple-C; however, there was minimal age difference between dual- and triple-P patients. Similar to the overall results from the TRANSLATE-ACS study (13), patients treated with prasugrel were younger and were more likely to be male than those treated with clopidogrel, regardless of oral anticoagulant use. In general, patients treated with triple therapy had a higher prevalence of cardiovascular comorbidities such as prior MI, revascularization, and heart failure, and were more likely to present with cardiogenic shock or heart failure compared with patients treated with DAPT, irrespective of the P2Y12 receptor inhibitor used. Rates of STEMI presentation and drug-eluting stent use were higher among patients treated with prasugrel regardless of oral anticoagulant use. Drug-eluting stents were used in 59% of patients discharged on triple-C and 74% among patients discharged on triple-P. Notably, an aspirin dose >81 mg was prescribed in approximately one-third of patients discharged on triple therapy (44% among prasugrel-treated and 34% among clopidogrel-treated patients) and approximately two-thirds of patients discharged on dual therapy. Overall, >4% of patients were lost to follow-up at 6 months and >5% at 12 months for each discharge group.
Any BARC-defined bleeding
At 6 months post-discharge, triple-C was associated with a significantly higher risk of any BARC-defined bleeding compared with dual-C after multivariable analysis (28.7% vs. 19.7%, adjusted incidence rate ratio [IRR]: 1.68, 95% confidence interval [CI]: 1.29 to 2.18; p = 0.0001) (Table 2). Similarly, triple-P was associated with significantly higher any BARC bleeding compared with dual-P (38.5% vs. 26.7%, adjusted IRR: 1.88, 95% CI: 1.10 to 3.20; p = 0.02). Among patients treated with triple therapy, triple-P was associated with significantly higher bleeding compared with triple-C (39.0% vs. 24.4%, adjusted IRR: 2.37, 95% CI: 1.36 to 4.15; p = 0.003).
Bleeding involving rehospitalization and patient-reported–only bleeding
Bleeding events were stratified into those that involved rehospitalization and those that were patient-reported only. As shown in Table 3, triple therapy was associated with significantly higher risks of rehospitalized bleeding compared with DAPT, regardless of P2Y12 receptor inhibitor choice. However, there was no significant difference between triple-P and -C (adjusted odds ratio [OR]: 0.62, 95% CI: 0.20 to 1.93) for bleeding involving rehospitalization. Triple-P was associated with significantly higher adjusted risk of patient-reported–only bleeding than triple-C (adjusted OR: 3.19, 95% CI: 1.52 to 6.66; p = 0.002).
Bleeding subtypes and severity
Bleeding events that were patient-reported only and did not involve rehospitalization were classified into BARC type 1 (not requiring patient to solicit medical attention) and BARC type 2 (prompted evaluation). There was no significant difference between triple therapy versus DAPT groups for BARC type 1 bleeding (Table 4), but triple therapy was associated with significantly higher BARC type 2 patient-reported–only bleeding for triple- compared with dual-C (adjusted IRR: 2.06, 95% CI: 1.50 to 2.82; p < 0.0001). Among patients on triple therapy, triple-P was associated with significantly higher patient-reported bleeding than triple-C, regardless of BARC type. Bleeding events involving rehospitalization were classified into BARC types 2 through 5 with event rates shown in Table 4. For comparisons with low event rates for BARC bleeding types 3 through 5, adjusted analyses were not performed.
Overall rates of GUSTO moderate/severe bleeding within 6 months after acute MI were low. Among clopidogrel-treated patients, GUSTO moderate/severe bleeding occurred in 21 patients (4.1%) treated with triple-C versus 109 patients (1.4%) treated with dual-C (adjusted hazard ratio [HR]: 3.31, 95% CI: 1.49 to 7.37). One triple-P patient (1.1%) developed GUSTO moderate/severe bleeding by 6-month follow-up compared with 26 patients (0.8%) treated with dual-P.
Major adverse cardiovascular events
Bleeding and ischemic outcomes on the basis of admission oral anticoagulant status
Among patients who were discharged on triple therapy (n = 617), 231 (37%) were on oral anticoagulant therapy prior to admission for their index MI. There was no significant association between oral anticoagulation use prior to admission versus no home oral anticoagulation use and MACE at 6 months (HR: 1.07, 95% CI: 0.60 to 1.91; p = 0.81). In addition, there was no significant association for either any BARC-defined bleeding (HR: 1.01, 95% CI: 0.66 to 1.57; p = 0.95) or ordinal BARC bleeding at 6 months (patient-reported bleeding vs. no bleeding: OR: 1.01, 95% CI: 0.57 to 1.76; p = 0.98; validated bleeding vs. no bleeding: OR: 1.17, 95% CI: 0.52 to 2.60; p = 0.71).
The TRANSLATE-ACS study offers a unique opportunity to examine the longitudinal risks of oral anticoagulant use among a contemporary cohort of MI patients treated with PCI and either clopidogrel or prasugrel in the United States. In this study, 617 patients were discharged on triple therapy; of these, 526 patients were treated with clopidogrel and 91 were treated with prasugrel. Our findings suggest that acute MI patients discharged on triple therapy had a greater risk of bleeding than those discharged on dual therapy, regardless of which P2Y12 receptor inhibitor was used. Among patients discharged on triple therapy, the use of prasugrel was associated with a higher risk of bleeding than clopidogrel. This association was largely driven by an increase in patient-reported–only bleeding; we observed no significant difference in the risk of bleeding requiring rehospitalization between these 2 groups. Finally, there was no significant difference in the composite risk of MACE between treatment groups.
Expert consensus documents have provided recommendations on antithrombotic therapy regimens for patients with recent MI and/or PCI and atrial fibrillation based on assessments of the need for prophylaxis against stroke, stent thrombosis, or other MACE (14). Yet, to date, most studies evaluating bleeding and cardiovascular outcomes associated with triple therapy have been nonrandomized in design, predominantly retrospective, and mostly in the setting of clopidogrel use (15–17). Sorensen et al. (18) demonstrated that in MI patients, the yearly incidence bleeding requiring rehospitalization was 3.7% for aspirin plus clopidogrel versus 12.0% for triple therapy. Among patients with both MI and atrial fibrillation, antithrombotic intensification was similarly associated with increased bleeding risk. Relative to aspirin alone, the HR was 1.22 for aspirin + clopidogrel, 1.46 for aspirin + warfarin, and 1.65 for aspirin + clopidogrel + warfarin (19).
Prasugrel is a higher-potency P2Y12 receptor inhibitor proven to have superior efficacy in reducing downstream cardiovascular events when compared with clopidogrel. Nonetheless, prasugrel is associated with a higher risk of bleeding (9), which leads to hesitation for its use with oral anticoagulant therapy. Our study showed that prasugrel was received in approximately 1 in 7 patients (15%) on triple therapy, and approximately 1 in 3 patients (31%) on DAPT. This finding suggests that physicians are less likely to add prasugrel to an oral anticoagulant and more likely to choose clopidogrel when prescribing DAPT with an oral anticoagulant. To date, Sarafoff et al. (20) described the largest cohort of patients treated with prasugrel and an oral anticoagulant. In this single-center cohort of patients undergoing drug-eluting stent implantation and discharged on oral anticoagulation, 21 of 377 patients received prasugrel (20). Prasugrel-treated patients had significantly higher rates of Thrombolysis In Myocardial Infarction major and minor bleeding at 6 months compared with clopidogrel-treated patients (6 [28.6%] vs. 24 [6.7%]; adjusted HR: 3.2, 95% CI: 1.1 to 9.1). Of the 377 patients on triple therapy in this study, only 139 (37%; 14 on prasugrel and 125 on clopidogrel) presented with acute coronary syndrome.
Our cohort is a larger sample of acute MI patients treated with PCI at more than 200 hospitals in the United States. In a previous analysis of the TRANSLATE-ACS study, patients discharged on higher-potency P2Y12 receptor inhibitors were shown to be more likely to have early post-discharge bleeding than patients discharged on clopidogrel; however, the majority of bleeding events were patient-reported only and did not require rehospitalization (21). In our analysis of patients discharged on oral anticoagulation therapy, we again observed a higher risk of bleeding when patients were concurrently treated with prasugrel versus clopidogrel. When bleeding events were divided into those requiring rehospitalization versus those that did not, we again demonstrated that the increase in bleeding seen with prasugrel was primarily driven by more minor patient-reported–only bleeding not requiring rehospitalization. Although our cohort size is still modest, our findings are reassuring in that we observed no significant difference in rehospitalized bleeding risk between prasugrel and clopidogrel, and only 1 of 91 patients on triple-P developed GUSTO moderate/severe bleeding. Although, the rate of MACE was higher for patients discharged on triple-P compared with triple-C, we found no significant differences after adjustment. Nevertheless, given that patients receiving triple therapy are less likely to be prescribed prasugrel, we may not be fully accounting for selection bias in this observational study. Further investigation is needed to elucidate specific subgroups of patients for whom triple therapy with prasugrel is preferable or cautioned.
Prior studies have shown the risk of bleeding to be higher with triple therapy compared with DAPT (18,22). In the TRANSLATE-ACS study, we found a similar association between increased risk of bleeding and triple therapy, regardless of antiplatelet agent choice. Although the TRANSLATE-ACS study did not evaluate interventions to mitigate bleeding risk in triple therapy patients, several points of interest were noted. First, a substantial number of patients treated with triple therapy were still discharged on high-dose aspirin; therefore, lowering concomitant aspirin dose may improve bleeding risk. Second, in the WOEST (What is the Optimal Antiplatelet and Anticoagulant Therapy in Patients With Oral Anticoagulation and Coronary Stenting) trial, DeWilde et al. (23) were able to show less bleeding and no increase in the rate of thrombotic events when clopidogrel was administered alone (without aspirin) in conjunction with an oral anticoagulant, in comparison to triple therapy; however, the WOEST trial primarily studied lower-risk patients, the majority of whom did not have acute coronary syndromes, who underwent PCI. Finally, rates of drug-eluting stent use are also high in the anticoagulated population. Minimizing the duration of antiplatelet therapy with bare-metal stent selection may also improve bleeding risk (24).
First, TRANSLATE-ACS was a voluntary observational study. Neither the selection of P2Y12 receptor inhibitor therapy nor the designation of oral anticoagulant in combination with a P2Y12 receptor inhibitor was assigned in a randomized manner. Therefore, despite rigorous multivariable adjustment, residual selection bias and unmeasured confounding likely remains. Second, although this is the largest cohort described so far, the number of patients that received triple-P was very low. Finally, the small number of patients discharged on prasugrel limits our ability to adjust for potential confounding and attenuates the strength of the derived conclusions.
In this observational study of contemporary MI patients treated with PCI and either clopidogrel or prasugrel, we observed a significantly higher risk of bleeding when an oral anticoagulant was added to DAPT. Triple therapy with prasugrel was prescribed to a select group of patients and was associated with a higher risk of any BARC bleeding compared with triple therapy with clopidogrel; however, this increase in risk was primarily observed for patient-reported bleeding that did not require rehospitalization. In contrast, we observed no significant difference in the risk of rehospitalized bleeding between triple-P and -C groups. Data from larger studies are needed to determine the overall benefit of different P2Y12 receptor inhibitor regimens in patients requiring both systemic anticoagulation and DAPT after a recent MI and/or PCI.
WHAT IS KNOWN? Prior studies have shown significant bleeding risk among MI patients receiving PCI and treated with triple therapy (i.e., oral anticoagulant, P2Y12 receptor inhibitor, and aspirin).
WHAT IS NEW? We found that among MI patients, the addition of an oral anticoagulant was associated with a significantly greater risk of any BARC-defined bleeding relative to DAPT, regardless of which P2Y12 receptor inhibitor was selected. Among patients on triple therapy, prasugrel use was associated with higher patient-reported–only bleeding, but not bleeding requiring rehospitalization, than clopidogrel-treated patients.
WHAT IS NEXT? Data from larger studies are needed to determine the overall benefit of different P2Y12 receptor inhibitor regimens in patients requiring both systemic anticoagulation and DAPT after a recent MI and/or PCI.
For supplemental figures and tables, please see the online version of this article.
The TRANSLATE-ACS study is sponsored by Daiichi-Sankyo, Inc., and Lilly USA. The Duke Clinical Research Institute is the coordinating center for this study, which represents a collaborative effort with the American College of Cardiology. Dr. Zettler is an employee of Eli Lilly & Company. Dr. Cohen has received research grant support from Eli Lilly, Daiichi-Sankyo, and AstraZeneca; and has received consulting fees and speaking honoraria from Eli Lilly and AstraZeneca. Dr. Stone reports has served as a consultant to Eli Lilly, Daiichi-Sankyo, and AstraZeneca (all modest). Dr. Baker is an employee of Daiichi-Sankyo, Inc. Dr. Effron is an employee and shareholder of Eli Lilly & Company. Dr. Peterson has received institutional grant support from: the American College of Cardiology, the American Heart Association, Eli Lilly, Janssen; has received consulting fees (including CME) from: Merck & Co., Boehringer Ingelheim, Genentech, Janssen, and Sanofi. Dr. Wang has received research grant support from: Eli Lilly, Daiichi-Sankyo, AstraZeneca; Bristol-Myers Squibb, Boston Scientific, Gilead, GlaxoSmithKline, and Regeneron; consulting services from: Eli Lilly, AstraZeneca, and Premier. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.
- Abbreviations and Acronyms
- Bleeding Academic Research Consortium
- confidence interval
- dual antiplatelet therapy
- Global Use of Strategies to Open Occluded Arteries
- hazard ratio
- incidence rate ratio
- major adverse cardiac event(s)
- myocardial infarction
- odds ratio
- percutaneous coronary intervention
- ST-segment elevation myocardial infarction
- Received August 5, 2015.
- Accepted August 13, 2015.
- American College of Cardiology Foundation
- Connolly S.,
- Pogue J.,
- Hart R.,
- et al.,
- for the ACTIVE Writing Group of the ACTIVE Investigators
- Lamberts M.,
- Gislason G.H.,
- Olesen J.B.,
- et al.
- Levine G.N.,
- Bates E.R.,
- Blankenship J.C.,
- et al.
- Chin C.T.,
- Wang T.Y.,
- Anstrom K.J.,
- et al.
- Mehran R.,
- Rao S.V.,
- Bhatt D.L.,
- et al.
- ↵Wang TY, Anstrom K, Effron MB, et al. TRANSLATE-ACS: a large-scale registry comparing patterns of use and one-year outcomes with prasugrel versus clopidogrel in patients with acute myocardial infarction undergoing percutaneous coronary intervention. Paper presented at: Transcatheter Cardiovascular Therapeutics (TCT) Conference; September 2014; Washington, DC.
- Lip G.Y.,
- Windecker S.,
- Huber K.,
- et al.
- Holmes D.R. Jr..,
- Kereiakes D.J.,
- Kleiman N.S.,
- Moliterno D.J.,
- Patti G.,
- Grines C.L.
- Karjalainen P.P.,
- Porela P.,
- Ylitalo A.,
- et al.
- Sorensen R.,
- Hansen M.L.,
- Abildstrom S.Z.,
- et al.
- Sarafoff N.,
- Martischnig A.,
- Wealer J.,
- et al.
- Wang T.Y.,
- McCoy L.,
- Henry T.D.,
- et al.
- ↵ClinicalTrials.gov. A study exploring two strategies of rivaroxaban (JNJ39039039; BAY-59–7939) and one of oral vitamin k antagonist in patients with atrial fibrillation who undergo percutaneous coronary intervention (PIONEER AF-PCI). January 29, 2015. Available at: https://clinicaltrials.gov/ct2/show/NCT01830543. Accessed February 2, 2015.