Author + information
- Received March 4, 2016
- Accepted March 15, 2016
- Published online May 31, 2016.
- Dean J. Kereiakes, MDa,
- Robert W. Yeh, MDb,c,d,
- Joseph M. Massaro, PhDc,e,
- Donald E. Cutlip, MDb,c,f,
- P. Gabriel Steg, MDg,h,i,j,
- Stephen D. Wiviott, MDb,k,
- Laura Mauri, MDb,c,k,∗ (, )
- DAPT Study Investigators
- aChrist Hospital Heart and Vascular Center and The Lindner Center for Research and Education, Cincinnati, Ohio
- bHarvard Medical School, Boston, Massachusetts
- cHarvard Clinical Research Institute, Boston, Massachusetts
- dThe Smith Center for Outcomes Research in Cardiology, Beth Israel Deaconess Medical Center, Boston, Massachusetts
- eBoston University School of Public Health, Boston, Massachusetts
- fDepartment of Medicine, Cardiology Division, Beth Israel Deaconess Medical Center, Boston, Massachusetts
- gUniversité Paris-Diderot, Paris, France
- hINSERM U-1148, Hôpital Bichat, Paris, France
- iDépartement Hospitalo-Universitaire Fibrosis, Inflammation, and Remodeling, Assistance Publique–Hôpitaux de Paris, Paris, France
- jNational Heart and Lung Institute, Institute of Cardiovascular Medicine and Science, Royal Brompton Hospital, Imperial College, London, United Kingdom
- kDepartment of Cardiovascular Medicine, Brigham and Women’s Hospital, Boston, Massachusetts
- ↵∗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 DAPT (Dual Antiplatelet Therapy) study enrolled patients after coronary stenting. Patients randomized to continued thienopyridine and aspirin after 12 months had lower ischemic risk but higher bleeding risk than those treated with placebo and aspirin.
Objectives This study sought to determine whether a decision tool (DAPT score) aids prescription of dual antiplatelet therapy duration in patients with or without prior myocardial infarction (MI) treated with coronary stents.
Methods Patients were categorized according to any history of MI before the index procedure or no history of MI. Risk differences during the randomized treatment period (12 to 30 months) for ischemic (MI and/or stent thrombosis) and bleeding (Global Utilization of Streptokinase and Tissue Plasminogen Activator for Occluded Arteries moderate/severe) events were compared according to DAPT score.
Results Rates of MI were 3.8% versus 2.4% (p = 0.01) for patients with any MI versus no MI. Continued thienopyridine reduced late MI compared with placebo regardless of MI history (hazard ratio [HR] for any MI: 0.46; p < 0.001; HR for no MI: 0.60; p = 0.003) and increased bleeding (HR: 1.86, p = 0.01 any MI; HR: 1.58, p = 0.01 no MI). DAPT scores ≥2 were associated with reductions in MI/stent thrombosis with continued thienopyridine compared with placebo (2.7% vs. 6.0%, p < 0.001 any MI; 2.6% vs. 5.2%, p = 0.002 no MI), with comparable bleeding rates. Among patients with DAPT scores <2 in both groups, continued thienopyridine was associated with significantly increased bleeding but similar rates of ischemia.
Conclusions Patients with previous MI have greater risk of late ischemic events than those with no MI history. The DAPT score improves prediction of patient benefit and harm from continued dual antiplatelet therapy beyond assessment of MI history alone. (The Dual Antiplatelet Therapy Study; NCT00977938).
Patients with a history of myocardial infarction (MI) or presenting with acute coronary syndrome (ACS) have higher rates of recurrent ischemia following percutaneous coronary intervention (PCI) than those presenting with stable angina; clinical practice guidelines recommend their treatment include more aggressive risk factor modification and prolonged antiplatelet therapy (1). In the DAPT (Dual Antiplatelet Therapy) study, the risks of MI and stent thrombosis (ST) beyond 1 year after PCI were reduced by continued thienopyridine therapy (clopidogrel or prasugrel) in combination with aspirin (vs. placebo plus aspirin) (2,3), with a larger absolute event reduction observed among those patients whose stent was placed as treatment for ACS (4). The PEGASUS (Prevention of Cardiovascular Events in Patients With Prior Heart Attack Using Ticagrelor Compared to Placebo on a Background of Aspirin) trial was conducted among patients with a history of MI 1 to 3 years before enrollment, but no ACS within 12 months. Continued treatment with ticagrelor in combination with aspirin (vs. placebo plus aspirin) was associated with a reduction in major adverse cardiovascular events (5). In both studies, continuation of platelet P2Y12 inhibition was associated with increased bleeding risk.
The DAPT score is a novel decision tool that was recently developed to determine, among patients eligible for long-term dual antiplatelet therapy, those more likely to derive benefit (vs. harm) from long-term therapy (6). The ability of the DAPT score to effectively stratify relative ischemic benefit versus bleeding risk associated with prolonged thienopyridine therapy among patients with established ischemic risk (ACS or prior MI) and those without a history of MI is unknown. Thus, we analyzed ischemic and bleeding events among patients enrolled into the DAPT study by MI status (prior MI, index MI, any MI, or no MI) and DAPT score among eligible patients randomized to continued thienopyridine (vs. placebo) therapy in combination with aspirin between 12 and 30 months following PCI.
The DAPT study was a double-blind, international, multicenter, randomized, placebo-controlled trial designed to compare 30 with 12 months of aspirin plus thienopyridine therapy (clopidogrel or prasugrel) after coronary stenting with either drug-eluting stents or bare-metal stents. The study design (7) and results (2–4,8) have been described previously, as has the DAPT score (6).
The present exploratory analysis of patients who tolerated dual antiplatelet therapy for 1 year was designed to evaluate the risk of ischemic and bleeding events according to the time interval between presentation with MI and PCI; and determine the ability of the DAPT score to predict relative benefit (vs. harm) from continued thienopyridine therapy among individual patients beyond the benefit-risk strata conferred by MI status (any or none) alone.
Study population and procedures
After PCI with either drug-eluting stents or bare-metal stents, patients who were candidates for dual antiplatelet therapy were enrolled and treated with open-label thienopyridine (clopidogrel or prasugrel) in combination with aspirin for 12 months. At 12 months, patients without a major adverse cardiovascular or cerebrovascular event, repeat revascularization, or moderate or severe bleeding but who were compliant with dual antiplatelet therapy were randomized to receive thienopyridine plus aspirin or placebo plus aspirin for an additional 18 months. At 30 months, the randomized study drug was discontinued; all patients remained on aspirin alone and were followed for another 3 months. The institutional review board at each participating institution approved the study and all patients provided written, informed consent.
For the purposes of this study, patients were categorized according to the timing of MI, with “index MI” occurring within 72 h before the index PCI, “prior MI” defined as occurring more than 72 h before the index PCI, “no MI” described patients with neither index nor prior MI, and “any MI” used to describe patients with either index or prior MI.
All endpoints were adjudicated by a clinical events committee blinded to treatment assignment and administered by the Harvard Clinical Research Institute. A central data safety monitoring board and an independent biostatistician reviewed unblinded data from all patients on a regular basis.
DAPT score assessment, the primary ischemic endpoint was a composite of MI or Academic Research Consortium–defined definite or probable ST (MI/ST) (9) and the primary bleeding endpoint was GUSTO (Global Utilization of Streptokinase and Tissue Plasminogen Activator for Occluded Arteries) moderate or severe bleeding (10). Other endpoints included death, MI, major adverse cardiovascular or cerebrovascular events, and Bleeding Academic Research Consortium-defined bleeding (11).
The derivation and validation of the DAPT score has previously been described for all randomized patients in the DAPT study (6). The DAPT score, ranging from -2 to 10, included several variables pertinent to event risk (Central Illustration). Overall, lower DAPT scores were associated with higher bleeding risk (with or without continued thienopyridine therapy) and less ischemic benefit from treatment, whereas higher DAPT scores were associated with lower bleeding risk and larger absolute ischemic benefit.
We compared endpoint events during the 12 months before randomization between patients with any MI and patients with no MI using the chi-square test. We compared Kaplan-Meier estimates of endpoint events occurring between 12 and 30 months after stenting by randomized treatment arm, using log-rank p value stratified by geographic region (North America, Europe, or Australia and New Zealand), thienopyridine type received at the time of randomization, and presence or absence of risk factors for ST. We assessed these endpoints within 5 groups of patients, those with: 1) index MI; 2) prior MI; 3) both index and prior MI; 4) no MI; and 5) any (either index or prior) MI. Patients not experiencing the endpoints between 12 and 30 months were censored at the time of last known contact or 30 months, whichever was earlier.
The consistency of the treatment effect between patients with any MI and patients with no MI was evaluated through Cox proportional hazards regression models with the main effects of randomized treatment and MI status and the inclusion of MI status analyzed by randomized-treatment interaction term. We also assessed the interaction of randomized treatment by MI status within DAPT score groups.
Randomized patients with any MI or no MI were divided into 4 groups, defined by the overall randomized population DAPT score quartiles (quartile 1 = −2 to 0 points; quartile 2 = 1 point; quartile 3 = 2 points; and quartile 4 = 3 to 9 points) and according to the median value of the DAPT score in the overall randomized population (DAPT score <2 vs. ≥2). The observed 12- to 30-month Kaplan-Meier event rates were compared within each score quartile across randomized treatment arm (continued thienopyridine vs. placebo). Because paclitaxel-eluting stents have been associated with higher thrombotic risk (12,13) and are not commonly used, event rates were additionally examined among patients not treated with 1 of these stents.
All statistical analyses were conducted at Harvard Clinical Research Institute with SAS software, version 9.2. (SAS Institute Inc., Cary, North Carolina). The authors (L.M., J.M.M.) had full access to the data and vouch for the integrity of the analyses presented. All analyses were performed on randomized subjects according to the intention-to-treat principle. A 2-sided p value of ≤0.05 was considered statistically significant for all analyses.
Of 25,682 patients enrolled in the DAPT study, 7,119 had an index MI and 5,900 had a prior MI (1,581 had both a prior MI and index MI), totaling 11,501 with any MI, whereas 14,181 had no MI. After 12 months of open-label treatment with dual antiplatelet therapy, 11,648 eligible patients were randomized to continued thienopyridine or placebo. Of these, 2,456 patients had prior MI (median, 891 days before stenting), 3,576 had an index MI (692 had both and were included in the prior MI and index MI groups, with their characteristics and outcomes separately presented in Online Tables 1 to 3), totaling 5,340 with any MI and 6,308 with no MI (Table 1, Figure 1). Compared with randomized patients with no MI, randomized patients with any MI were more likely to be cigarette smokers and male, whereas randomized patients with no MI were older and more likely to have diabetes, congestive heart failure, or hypertension compared with those with any MI.
Impact of MI on subsequent clinical events: Open-label treatment period (0 to 12 months post-PCI)
During the first 12 months after PCI, death (1.6% vs. 1.1%), MI (3.4% vs. 2.2%), and ST (0.7% vs.0.4%) rates were higher among enrolled patients with any MI versus those with no MI (all p < 0.001); GUSTO moderate or severe bleeding was lower among patients with any MI (2.2% vs. 3.1% for no MI; p < 0.001); but rates of noncompliance with dual antiplatelet therapy were similar (6.2% vs. 6.3%; p = 0.82) (Table 2), whereas rates of proton pump inhibitor use were higher for patients with no MI (21.2% vs. 22.8%; p = 0.04).
Impact of MI on subsequent clinical events: Randomized treatment period (12 to 30 months post-PCI)
Patients who had been treatment adherent and were event-free at 12 months were randomized. During the 18-month randomized treatment period, patients with any MI had higher rates of recurrent MI compared with patients with no MI (3.8% vs. 2.4%; p = 0.01) (Table 3), and lower rates of moderate/severe bleeding (1.6% vs. 2.2%; p = 0.02). The hazard ratio (HR) for MI reduction for continued thienopyridine versus placebo was 0.56 for prior MI, 0.42 for index MI, and 0.60 for no MI (interaction p = 0.29 for any MI vs. no MI). Absolute risk reduction with continued thienopyridine was 2.5% for prior MI, 3.0% for index MI, and 1.1% for no MI. Bleeding risk increases were 0.5%, 1.1%, and 1.0%, respectively (Online Table 1). At 30 months post-PCI, 20.5% of patients with prior MI had discontinued study drug, as had 18.0% with index MI, 18.7% with any MI, and 21.7% with no MI.
DAPT score distribution and clinical outcome
Among randomized patients with no MI, the median DAPT score was 1; a total of 2,210 (35.0%) had a high (≥2) DAPT score and 4,098 (65.0%) had a low (<2) DAPT score. In randomized patients with any MI, the median DAPT score was 2 (p < 0.0001 compared with median score in patients with no MI); 3,707 (69.4%) had a high and 1,633 (30.6%) had a low score (Figure 2).
Among patients with DAPT scores ≥2, continued thienopyridine (vs. placebo) was associated with reductions in MI/ST regardless of MI status at presentation (2.7% vs. 6.0%, p < 0.001 for any MI; 2.6% vs. 5.2%, p = 0.002 for no MI; interaction p = 0.68). Rates of GUSTO moderate or severe bleeding were 1.5% versus 1.1% (p = 0.24) for continued thienopyridine compared with placebo among those with any MI and 2.2% versus 2.0% (p = 0.68) for those with no MI (interaction p = 0.59).
Among patients with DAPT scores <2, in both groups, continued thienopyridine use was associated with increased bleeding compared with placebo (any MI, 3.2% vs. 1.2%, p = 0.01; no MI, 2.9% vs. 1.6%, p = 0.004; interaction p = 0.38), and MI/ST rates of 2.1% versus 3.2% in the any MI group (p = 0.17) and 1.5% versus 2.0% in the no MI cohort (p = 0.21; interaction p = 0.76) (Online Tables 4 and 5, Central Illustration, Figures 3 and 4).
At 12 to 30 months post-stenting in 5,340 patients with any MI, MI/ST occurred in 2.7% of thienopyridine users versus 6.0% for the placebo group (p < 0.001) in patients with a high DAPT score, and 2.1% versus 3.2% (p = 0.17) in patients with a low score; and GUSTO moderate or severe bleeding occurred in 1.5% versus 1.1% (p = 0.24) of patients with a high DAPT score and in 3.2% versus 1.2% (p = 0.01) of patients with a low score, respectively (Online Table 5, Central Illustration, Figures 3 and 4). Results were consistent among randomized patients not treated with paclitaxel-eluting stents (Online Figure 1).
This exploratory analysis of the DAPT study examines clinical ischemic and bleeding outcomes among enrolled patients stratified by history of MI and time interval since MI occurrence; the benefit versus risk relationship of prolonged (30 vs. 12 months) thienopyridine therapy among all randomized patients stratified by MI status; and whether a tool to individualize treatment decision regarding continued thienopyridine therapy, the DAPT score, could enhance the assessment of potential benefit and risk compared with decision making based on MI status alone.
The major findings of this study were: 1) patients with any MI before PCI had increased risk for ischemic events (vs. patients with no MI) in the year after PCI despite dual antiplatelet therapy; 2) patients with any MI had higher rates of ischemic events (MI, ST) than did patients with no MI between 12 and 30 months following PCI; 3) although the relative treatment benefit (ischemic event reduction) of thienopyridine therapy (vs. placebo) between 12 to 30 months post-PCI was consistent across patient cohorts stratified by MI status, absolute reductions in ischemic event rates were numerically greater among patients with any MI (vs. no MI); and 4) the DAPT score further stratified individual patients according to expected treatment benefit versus harm of dual antiplatelet therapy beyond 1 year post-PCI compared with MI status only to determine duration of therapy prescription. It did so by identifying patients with MI who are more likely to be harmed and patients with no previous MI who are more likely to be benefitted. Analyses excluding paclitaxel-eluting stent–treated subjects showed similar utility of the DAPT score.
The present analysis both confirmed and extended prior observations regarding the persistent relative ischemic hazard following MI and the larger absolute treatment benefit of dual antiplatelet therapy beyond 1 year in patients with, versus those without, MI. Early ischemic hazard following PCI for ACS has been ascribed to an increased risk of ST and to events unrelated to stented coronary segments caused by the multicentric, multivessel nature of vulnerable plaque within the epicardial coronary tree. Furthermore, ischemic events occurring beyond 1 year after coronary stenting most frequently have been nontarget-lesion-related events regardless of stent type (bare-metal stents or drug-eluting stents) (14,15). Finally, stent healing and endothelial coverage are more often incomplete following stent strut deployment into necrotic core plaque. Together, these observations support the premise of increased magnitude and duration of risk for ischemic events following ACS presentation, whether or not PCI is performed.
Consistent with this observed increase in ischemic risk among patients with ACS have been observations of greater ischemic event suppression with prolonged platelet inhibition. Although most studies focused on early events after ACS, the DAPT study primarily evaluated patients who had been stable for 1 year after presentation and, in this setting, any prior history of MI classified patients to a higher-risk group for recurrent ischemic events. In fact, a prior analysis of patients presenting with index MI and randomized in the DAPT study demonstrated that index MI patients (compared with those without index MI) derived a relatively greater absolute benefit for MI reduction (particularly MI not related to ST) and had a similar (both absolute and relative) increased risk for bleeding with prolonged (30 vs. 12 months) duration thienopyridine plus aspirin therapy compared with placebo plus aspirin alone. Similarly, a recent large study of patients with a history of MI (with or without stent treatment) 1 to 5 years before enrollment demonstrated a significant reduction in recurrent MI and an associated significant increase in bleeding events following P2Y12 receptor inhibition with ticagrelor compared with placebo (both in combination with aspirin) (5). Thus, even 1 to 5 years following presentation for MI, the addition of P2Y12 inhibition to aspirin significantly reduced recurrent ischemic events regardless of prior PCI treatment, at the cost of increased bleeding.
The current analysis demonstrated that regardless of the timing of prior or index MI and despite the absence of events during the 12 months before randomization, patients with any MI derived a larger absolute reduction in ischemic events when treated with 30 (vs. 12) months of thienopyridine therapy compared with patients with no MI. Interestingly, patients with no MI had a greater risk of bleeding both within and beyond the first 12 months after PCI compared with patients having any MI. This may be attributed to the older average age of patients with no MI versus any MI. The combination of higher absolute ischemic risk and treatment benefit along with lower bleeding risk in subjects with any MI amplified the overall benefit of continued thienopyridine therapy treatment and was consistent with prior studies (16).
Clinical utility of the DAPT risk score
In a prior DAPT study analysis of randomized patients with index MI (ST- or non-ST-segment elevation MI), fatal (Bleeding Academic Research Consortium type 5) bleeding was rare and not different by duration of thienopyridine therapy (regardless of index MI status), and the absolute increases in major bleeding events associated with prolonged thienopyridine therapy were similar (1.1% index MI, 0.9% no index MI). Nonetheless, although patients with index MI had large absolute and relative risk reduction in ischemic events with continued thienopyridine therapy, there remained a significant risk of bleeding in this population (HR for major bleeding: 2.38; 95% confidence interval: 1.27 to 4.43; p = 0.005). Additionally, among patients without index MI, continued thienopyridine therapy was associated with significant reduction in MI and ST rates. Thus, optimization of therapy for individual patients to minimize these counterbalancing risks is complex and not simply determined by MI status. Indeed, although patients with any (vs. no) MI in the present study derived greater absolute reductions in risk for MI/ST, the relative hazards for major bleeding events were similar (HR: 1.86; 95% confidence interval: 1.18 to 2.93; p = 0.01 for any MI; and HR: 1.58; 95% confidence interval: 1.12 to 2.24; p = 0.01 for no MI).
In prior analysis, the DAPT score was able to identify patients in the overall DAPT study with greater ischemic benefit (DAPT score ≥2) or greater bleeding risk (DAPT score <2). Higher DAPT scores indicated greater MI/ST reduction (p interaction < 0.001) and lower DAPT scores indicated greater bleeding risk increases (p interaction = 0.02) with continued thienopyridine therapy (6). Of note, the DAPT score includes a history of MI and, therefore, by definition patients with any MI would be expected to have higher scores. Nonetheless, in the current study, the score still differentiated between those who would benefit from or be harmed by continued thienopyridine use among patients within each of these groups. In this regard, it is noteworthy that 35% of the no MI cohort had high DAPT scores that would predict ischemic benefit exceeding bleeding risk, whereas 30% of the any MI cohort had low DAPT scores that would predict the opposite. Thus, almost one-third of the patients in either MI subgroup (any or no) might have been more accurately prescribed risk-appropriate duration of dual antiplatelet therapy based on DAPT score compared with MI status alone.
Indeed, among patients with any compared to no MI, DAPT scores <2 versus ≥2 distinguished between individual patients likely to be benefited versus harmed by continued antiplatelet therapy. The clinical utility of the DAPT score to improve decision making over the single subgroup classification by MI status was evident in terms of number needed to treat to benefit or harm (Table 4). The number needed to treat to benefit to avoid MI/ST in the no MI population was reduced from 84 to 40 when patients with a high DAPT score were selected. For patients with any MI, the number needed to treat to harm resulting in bleeding was increased from 106 to 226 when patients with a high DAPT score were selected.
Because some patients with MI have high risk of bleeding and some patients without MI have high risk of ischemia, using the determinant of MI history alone to decide treatment duration is inadequate. Importantly, the DAPT score allowed for more refined decision making and identified which patients with a history of MI have a risk of bleeding that outweighed any ischemic benefit from longer duration therapy. Conversely, among patients with no history of MI, a high DAPT score predicted ischemic risk reduction that outweighed bleeding risk. Thus, the DAPT score more accurately classified the benefit-risk relationship of prolonged (>12 months) thienopyridine therapy for individual patients beyond what can be attributed to MI history status alone.
This study’s main limitation is related to the post hoc subgroup nature of analysis. Second, although the DAPT score was derived from the global DAPT study population, treatment effects within each subgroup were underpowered. Additionally, one might expect that the score would perform well when applied to a subset of the dataset from which it was derived. Finally, we combined patients with prior MI and those with index MI for the purpose of interaction analysis. Although these groups were demographically dissimilar, they were similar with respect to risk for recurrent ischemic events, and MI (regardless of classification) occurred at least 1 year before randomized treatment allocation. This cohort is, therefore, lower risk than patients who have had an MI within the first year after PCI who would be recommended to continue dual antiplatelet therapy for an additional year according to current guidelines (17). Nevertheless, application of the DAPT score, even among patients at demonstrated increased ischemic risk, provided more accurate, individualized assessment of relative benefit (vs. risk) for prolonged (30- vs. 12-month) thienopyridine therapy than could be inferred from MI status alone.
Patients with any MI have an increased risk for ischemic events 12 to 30 months after PCI compared with patients with no MI despite treatment with dual antiplatelet therapy. Prolonged (>12 months) thienopyridine therapy provides a greater absolute reduction in ischemic events with a similar relative bleeding risk among patients with (vs. without) any MI. Among patients with MI eligible for prolonged thienopyridine therapy at 1-year post-PCI, the DAPT score seemed to provide a more accurate benefit versus risk assessment on which individualized thienopyridine therapy may be appropriately prescribed. A high DAPT score (≥2) predicted ischemic benefit without incremental bleeding risk with continued thienopyridine therapy beyond 1 year.
COMPETENCY IN PATIENT CARE AND PROCEDURAL SKILLS: The DAPT score may be useful in assessing the risks and benefits of continuing dual antiplatelet therapy for more than 12 months after coronary stenting. The score incorporates patient age, cigarette smoking, diabetes, myocardial infarction at presentation or earlier, prior coronary interventions, stent type and diameter, heart failure, and left ventricular ejection fraction. Among the additional factors to consider are medication compliance and the occurrence of major ischemic or bleeding events during the initial treatment period.
TRANSLATIONAL OUTLOOK: Prospective studies are required to validate the predictive value of the dual antiplatelet therapy score in diverse patient cohorts over shorter and longer periods of treatment exposure.
The authors thank Ms. Wen-Hua Hsieh and Ms. Patricia K. Apruzzese for their assistance with statistical analysis, and Ms. Joanna Suomi for her assistance with editing and formatting the manuscript.
Sponsored by Harvard Clinical Research Institute. 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. Kereiakes has received research funding and is a consultant to Abbott Vascular, Boston Scientific, and Sanofi. Dr. Yeh is on an Advisory Board for Abbott Vascular and for Boston Scientific; and is a consultant for Boston Scientific, Abbott Vascular, and Merck. Dr. Massaro has received funding from Harvard Clinical Research Institute for statistical services for the manuscript. Dr. Cutlip has received research funding (paid to his institution) from Medtronic, Boston Scientific, and Celonova. Dr. Steg has received research funding from Sanofi and Servier; is a consultant for Amarin, AstraZeneca, Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, CSL-Behring, Daiichi-Sankyo-Lilly, GlaxoSmithKline, Janssen, Medtronic, Merck-Sharpe Dohme, Novartis, Pfizer, Regeneron, Sanofi, Servier, and The Medicines Company; and is a stockholder in Aterovax. Dr. Wiviott has received grants and personal fees from AstraZeneca, Eli Lilly/Daiichi-Sankyo, Bristol-Myers Squibb, and Arena; grants from Eisai, Merck, and Sanofi; and personal fees from Aegerion, Angelmed, Janssen, Xoma, ICON Clinical, and Boston Clinical Research Institute. Dr. Wiviott’s wife is an employee of Merck Research Laboratories. Dr. Mauri has received grants (to her institution) from Abbott, Boston Scientific, Cordis, Medtronic, Eli Lilly and Company, Daiichi-Sankyo, Sanofi, Bristol-Myers Squibb, Boehringer Ingelheim, and Biotronik; and is a consultant for Medtronic, Eli Lilly and Company, Boehringer Ingelheim, AstraZeneca, Recor, and Biotronik.
- Abbreviations and Acronyms
- acute coronary syndrome(s)
- Dual Antiplatelet Therapy
- Global Utilization of Streptokinase and Tissue Plasminogen Activator for Occluded Arteries
- hazard ratio
- myocardial infarction
- percutaneous coronary intervention
- stent thrombosis
- Received March 4, 2016.
- Accepted March 15, 2016.
- American College of Cardiology Foundation
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