1
Duration of dual antiplatelet therapy and associated outcomes following percutaneous
coronary intervention for acute myocardial infarction: Contemporary practice insights
from the Canadian Observational Antiplatelet Study (COAPT)
Juan J Russo, MD1,2, Shaun G Goodman, MD, MSc1,3, Akshay Bagai, MD, MPH1, Jean-Pierre Déry,
MD4, Mary K Tan, MSc3, Harold N Fisher, MD5, Xiang Zhang, PhD6, Yajun Emily Zhu, MSc6, Robert
C Welsh, MD7, Anthony Della Siega, MD8, Andre Kokis, MD9, Brian YL Wong, MD10, Mark Henderson,
MD11, Sohrab Lutchmedial, MD12, Shahar Lavi, MD13, Shamir R Mehta, MD, MSc14, Andrew T Yan,
MD, on behalf of the COAPT investigators
From the 1Terrence Donnelly Heart Centre, St Michael’s Hospital, University of Toronto, Toronto, ON;
2
University of Ottawa Heart Institute, Ottawa, ON; 3Canadian Heart Research Centre, Toronto, ON;
Institut Universitaire de Cardiologie et de Pneumologie de Québec, Quebec City, QC; 5Eli Lilly Canada
4
Inc, Toronto, ON; 6Eli Lilly and Company, Indianapolis, IN; 7Mazankowski Alberta Heart Institute,
University of Alberta, VIGOUR Centre, Edmonton, AB; 8Royal Jubilee Hospital, Victoria Heart Institute,
Victoria, BC; 9Centre Hospitalier de l'Université de Montréal (CHUM), Montreal, QC;
10
Health
Sciences North, Sudbury, ON; 11Thunder Bay Regional Health Sciences Centre, Thunder Bay, ON; 12New
Brunswick Heart Centre, CardioVascular Research New Brunswick, Saint John, NB; 13London Health
Sciences Centre, Western University, London, ON; 14Hamilton Health Sciences, McMaster University,
Population Health Research Institute, Hamilton, ON.
Short Title: DAPT duration after PCI for myocardial infarction
Word count: 3622
Address for correspondence: Andrew T. Yan or Shaun G. Goodman, St. Michael’s Hospital,
Division of Cardiology, 30 Bond Street, Donnelly 6-030, Toronto, Ontario, Canada M5B 1W8.
Fax: 416-864-5159, Telephone: 416-864-5465, E-mail: [email protected] or [email protected]
2
Abstract
Aims: There is a paucity of real-world, contemporary data of practice patterns and clinical
outcomes following dual-antiplatelet therapy (DAPT) in acute myocardial infarction (AMI)
patients treated with percutaneous coronary intervention (PCI).
Methods and Results: The Canadian Observational Antiplatelet Study (COAPT) was
a prospective, multicenter, cohort study examining adenosine diphosphate (ADP) receptor
antagonist use following PCI for AMI. We compared practice patterns, patient characteristics,
and clinical outcomes in relation to DAPT duration (<6 weeks, 6 weeks to <6 months, 6 to <12
months, and ≥12 months). The primary outcome was the composite of non-fatal AMI, unplanned
coronary revascularization, stent thrombosis, new or worsening heart failure, cardiogenic shock,
or stroke. We identified 2034 patients with AMI treated with PCI. DAPT duration was <6 weeks
in 5.2% of patients; 6 weeks to <6 months in 7.0%; 6 to <12 months in 12.6%; and ≥12 months
in 75.3%. Patients who discontinued DAPT earlier had higher GRACE risk scores. Overall,
mortality rate at 15 months was 2.5%. Compared to a duration of DAPT of ≥12 months,
discontinuation of DAPT <6 weeks (p<0.0001) and 6 weeks to <6 months (p = 0.02), but not 6
months to <12 months (p=0.06), were independently associated with a higher incidence of the
primary outcome among survivors.
Conclusion: One-in-four patients with AMI treated with PCI discontinued DAPT prior to the
guideline-recommended 12-month duration. Patients in whom DAPT was discontinued early
were at higher baseline risk and had higher rates of non-fatal ischemic events during follow up.
Key words: myocardial infarction, angioplasty, dual antiplatelet therapy, cardiovascular
outcomes.
3
Introduction
The optimal duration of dual antiplatelet therapy (DAPT) following percutaneous
coronary intervention (PCI) has not been well established. Current guidelines recommend the
combination of aspirin and an adenosine diphosphate (ADP) receptor antagonist for at least 12
months following myocardial infarction, including those patients managed with PCI.1 DAPT in
this context prevents stent thrombosis and other ischemic events, but is associated with an
increased risk of bleeding.2-5 In contemporary practice, DAPT is often discontinued prior to the
guideline recommended duration of 12 months.6-8 A growing body of evidence now supports the
notion that a shortened duration of DAPT of 3 to 6 months may be sufficient to prevent stent
thrombosis in elective PCI patients, particularly with the newer generation stents.3, 9-11 In
contrast, the recent DAPT and Prevention of Cardiovascular Events in Patients With Prior Heart
Attack Using Ticagrelor Compared to Placebo on a Background of Aspirin (PEGASUS) trials
demonstrated that the use of DAPT beyond 12 months following PCI or acute myocardial
infarction (AMI) was associated with reduced major adverse cardiovascular events, albeit with
increased bleeding.12, 13 These studies suggest that the optimal duration of DAPT may be largely
dependent on patient characteristics, index event, and procedural details. The added complexity
of the decision-making process may translate to increased variability in practice patterns amongst
treating physicians and deviation from guideline recommendations. In the present retrospective
cohort study, we used contemporary registry data to examine real-world practice patterns, patient
characteristics, and clinical outcomes following PCI for AMI in relation to DAPT duration.
Methods
The Canadian Observational Antiplatelet Study (COAPT) was a prospective, multicenter,
longitudinal observational study examining ADP receptor antagonist use following PCI for acute
4
myocardial infarction. Patients ≥18 years of age undergoing PCI during their index admission for
non-ST segment elevation myocardial infarction (NSTEMI) or ST-segment elevation myocardial
infarction (STEMI) were included and followed for 15 months. Patients who did not receive an
ADP receptor antagonist or were enrolled in a clinical trial mandating specific antiplatelet or
anticoagulation therapy as part of the trial protocol were excluded. Initiation, maintenance, and
changes to treatment were solely at the discretion of the treating physician and the patient. The
target enrollment was 2200 consecutive AMI patients treated in PCI-capable hospitals in Canada.
All 43 PCI-capable hospitals across Canada were invited, and 26 sites participated in COAPT.
The study was approved by institutional research ethics boards and all patients provided
informed consent prior to participation.
The primary objective of COAPT was to examine real-world practice patterns of DAPT
use following PCI for acute myocardial infarction, and their association with patient and
treatment characteristics. Secondary objectives included an assessment of the incidence of
adverse events including death, myocardial infarction, ischemic stroke, unplanned coronary
revascularization, stent thrombosis, and bleeding events in relation to the type and duration of
ADP receptor antagonist therapy.
In the current analysis, we compared practice patterns, patient characteristics, and clinical
outcomes in relation to the duration of DAPT following PCI for AMI. We stratified patients a
priori into four DAPT duration intervals (<6 weeks, 6 weeks to <6 months, 6 to <12 months, and
≥12 months), and examined baseline patient characteristics, treatment variables, and adverse
events within each stratum. The timing of DAPT discontinuation was coded independently from
the reason for discontinuation–which may have included discontinuation as a result of death or
bleeding event. The primary cardiovascular outcome of the present analysis was the composite of
5
non-fatal myocardial infarction, unplanned coronary revascularization, stent thrombosis, new or
worsening heart failure, cardiogenic shock, or ischemic stroke at 15 months. The composite
cardiovascular outcome consisted of non-fatal events only to avoid confounding by reverse
causation (i.e. patients classified as having discontinued DAPT early as a result of death).
Secondary outcomes included death and bleeding events (any bleeding and bleeding as defined
by the Bleeding Research Academic Consortium).14
We present continuous variables using medians and interquartile ranges, and categorical
variables using percentages or frequencies. We compared continuous variables using the
Kruskal-Wallis test, and categorical variables using the χ2 test, or Fisher’s exact test when
appropriate. Trends were compared using the Jonckheere-Terpstra or the Cochran-Armitage
trend tests where appropriate. We provided odds ratios and 95% confidence intervals (CI) for all
endpoints analyzed.
Due to the non-randomized nature of this analysis, the independent association between
DAPT duration and the composite cardiovascular outcome was examined using three main
models, which included: 1) a complete-case propensity score adjusted analysis, 2) a completecase adjusted multilevel logistic regression analysis, and 3) a multiple imputed adjusted
regression model. Explanatory variables in the first and second models included duration of
DAPT, age, systolic blood pressure, heart rate, type of myocardial infarction (STEMI versus
NSTEMI), oral anticoagulant (OAC) therapy on discharge, cardiac arrest on presentation, and
previous history of myocardial infarction, PCI, heart failure, stroke or transient ischemic attack,
atrial fibrillation, coronary artery bypass grafting, hypertension, and dyslipidemia. In the third
model, we examined the association between key patient and treatment variables (including those
for which only <95% of the data were available) and the odds of the composite cardiovascular
6
outcome. Explanatory variables in this model included duration of DAPT (≥12 months compared
to <6 weeks, 6 weeks to <6 months, and 6 to <12 months), GRACE risk score (a validated
predictor of in-hospital mortality),15 type of MI (STEMI versus NSTEMI), treatment with OAC
on discharge, newer ADP receptor antagonist (ticagrelor or prasugrel versus clopidogrel), and the
composite of a previous history of PCI, MI, or CABG.
The propensity score adjusted analysis (model 1) was performed using marginal mean
weighting through stratification (MMWS). The MMWS was obtained by combining elements of
two propensity score based techniques, stratification and weighting.16 Multinomial logistic
regression was used to estimate the propensity scores, with four propensity scores estimated for
each patient. The region of common support was assessed to ensure that the resulting propensity
scores were within the common bound of minimum and maximum ranges. Propensity scores
were subsequently stratified into five similarly-sized quintiles per stratum in each DAPT
duration group. MMWS was then calculated in each stratum and DAPT duration group. Data
balance was assessed by adjusting with MMWS weights. A total of 1895 of 2034 patients were
analyzed in the propensity score model as: 1) there were 44 patients with no propensity score,
and 2) 95 patients had propensity scores outside the common region of support. We provide 2
adjusted estimates of the composite cardiovascular outcome: the first adjustment was obtained
using MMWS as weights only, and the second was further adjusted by introducing additional
covariates (used to construct the propensity score) to create a “doubly robust model”.16
In the second analysis (model 2), we examined the odds of the composite cardiovascular
outcome in relation to the duration of DAPT after adjusting for baseline differences in variables
potentially associated with the timing of DAPT discontinuation and for which >95% of the data
were available (complete case analysis). A multilevel random intercept model design was used to
7
adjust for variability related to practice patterns in individual participating sites. The intraclass
correlation coefficient was determined using an unconditional model with no predictor through
PROC GLIMMIX in SAS.
The third analysis (model 3) also included variables for which only <95% of the data
might have been available. In this model, GRACE risk score was unavailable in 30% of patients.
Multiple imputation was used to address missing data in the model under the assumption that
data were missing at random. A SAS default single Markov chain Monte Carlo method, which
assumes multivariate normality, was used to generate 20 complete datasets. All explanatory
variables and the composite cardiovascular outcome were used as auxiliary variables when
imputing missing data. The results of the complete models were combined (PROC
MIANALYZE in SAS) to generate inferences. In an exploratory analysis, we included DAPT
duration as a continuous variable, rather than a categorical variable, in models 2 and 3.
Statistical analyses were conducted using SAS 9.4 (SAS Institute, Cary, NC, USA). Twosided p values <0.05 were considered statistically significant.
Results
Of the initial enrolment target of 2200 patients, 2179 patients were enrolled in 26
Canadian PCI-capable hospitals between December 2011 and May 2013. Of these 2179 patients,
2034 were included in this analysis as they had been started on DAPT following PCI for AMI
and survived to hospital discharge. Upon discharge, clopidogrel was used in 72% of patients,
ticagrelor in 17%, and prasugrel in 11%. DAPT duration was ≥ 12 months in 1531 patients
(75.3%), 6 to <12 months in 256 (12.6%), 6 weeks to <6 months 142 (7.0%), and <6 weeks in
105 (5.2%).
8
Baseline patient characteristics stratified by duration of DAPT are summarized in Table
1. In comparison to patients who continued DAPT ≥ 12 months, patients who received a shorter
duration of DAPT were older, had higher creatinine levels, and a higher prevalence of atrial
fibrillation, prior myocardial infarction, PCI, heart failure, and stroke or transient ischemic
attack. Table 2 outlines the characteristics and treatment of the index AMI. Compared to
patients who received DAPT for ≥ 12 months, patients who received a shorter duration of DAPT
were at higher baseline risk as evidenced by their higher GRACE risk scores, less likely to have
received a drug-eluting stent, and more likely to be on an OAC upon discharge. Treatment
characteristics were otherwise well balanced between DAPT duration strata. Data regarding
reason for early DAPT discontinuation (defined as <12 months) were available for 325 patients
(65%). Among these patients, the most common reasons for early discontinuation of DAPT were
DAPT being deemed unneeded (49.5%) and other physician preference (29.5%). DAPT was
discontinued early due to adverse events in 7.0% of patients, need for oral anticoagulation in
2.5%, need for surgery in 2.5%, patient preference in 3.1%, and financial constraints in 1.2%.
Table 3 and figure 1 illustrate the unadjusted ischemic and safety outcomes in the overall
population and after stratification by the duration of DAPT. Mortality rate at 15 months in the
overall cohort was 2.5%: 21% in patients treated with DAPT <6 weeks, 11% in those treated for
6 weeks to <6 months, 3.1% for those treated for 6 to <12 months, and 0.3% in patients treated
for ≥12 months. The composite cardiovascular outcome occurred in 16.6% of patients, non-fatal
myocardial infarction in 9.4%, and stent thrombosis in 1.6%. There was a significant association
between a shorter duration of DAPT and increased rates of these adverse events. With regard to
ischemic outcomes specifically, the rates of myocardial infarction and unplanned coronary
revascularization correlated inversely with the duration of DAPT. In contrast, the rate of stent
9
thrombosis was comparable in patients who received DAPT for ≥6 weeks (1.3%), and
significantly higher in patients who received DAPT for <6 weeks (5.7%). There was also a
significant association between longer duration of DAPT and reduced rates of new or worsening
heart failure and cardiogenic shock. While the rates of any bleeding and need for blood
transfusions were similar between DAPT duration strata, there was an inverse relationship
between the incidence of BARC ≥2 bleeding and duration of DAPT.
The results of the propensity score analysis (model 1) are summarized in Table 4; in
addition, all variables included as covariates in the propensity score and their respective adjusted
odds ratios are listed in Supplementary Table 1. Shortened DAPT durations of <6 weeks and 6
weeks to < 6 months were associated with increased odds of the composite cardiovascular
outcome compared to a duration ≥12 months. Compared to a duration of ≥12 months,
discontinuation of DAPT between 6 to <12 months was associated with a non-significant trend
towards an increased odds of the composite cardiovascular outcome. Additional covariates
independently associated with an increased incidence of the composite cardiovascular outcome
included prescription of an oral anticoagulant on discharge and a previous history of heart
failure, stroke, or transient ischemic attack (Supplementary Table 1).
The results of the multivariable logistic regression analyses (models 2 and 3) are
summarized in supplementary Tables 2 and 3. In model 2, which used a multilevel random
intercept model design to account for variability in practice patterns in individual sites, the
intraclass correlation coefficient was 0.44 for the composite cardiovascular outcome. Compared
to a DAPT duration ≥12 months, a shortened duration of DAPT duration of < 6 weeks and 6
weeks to <6 months were independently associated with increased odds of composite
cardiovascular outcome in both models. Additional variables associated with increased odds of
10
the composite cardiovascular outcome included GRACE risk score, OAC on discharge, use of
clopidogrel (versus ticagrelor or prasugrel), and previous history of MI, PCI, and/or CABG were
independently associated with increased odds of the composite cardiovascular outcome
(supplementary Table 3).
In an exploratory analysis, increased DAPT duration as a continuous variable was
independently associated with lower odds of the composite cardiovascular outcome in models 2
(OR per 10 day increase = 0.984; 95%CI 0.977-0.992; p = 0.0001) and 3 (OR per 10 day
increase = 0.984; 95%CI 0.976-0.991; p <0.0001).
Discussion
The present study provides valuable insight into the contemporary use of DAPT
following PCI for AMI. Current ACC/AHA guidelines recommend continuing DAPT for ≥12
months following ACS.1 Although the majority of patients received DAPT for the guideline
recommended duration of ≥12 months, early discontinuation of DAPT occurred in approximately
25% of patients. Patients in whom DAPT was discontinued <12 months after PCI were older and
had higher risk profiles at baseline. There was an inverse correlation between the duration of
DAPT following PCI and the rates of non-fatal ischemic cardiovascular events, including
myocardial infarction and unplanned revascularization. While this was also true for stent
thrombosis, the rates of stent thrombosis did not seem to vary significantly when duration of
DAPT was ≥6 weeks. The overall rates of bleeding were comparable between DAPT duration
cohorts, but the incidence of more significant clinical bleeding (BARC ≥2) had a paradoxical
inverse correlation with the duration of DAPT – likely the result of confounding by reverse
causation (i.e. DAPT discontinuation due to bleeding event).
11
Although randomized controlled trials of ADP receptor antagonists generally used a 12month DAPT protocol, the duration of DAPT in these trials was arguably arbitrary.2, 4, 5 The
totality of the evidence regarding the optimal duration of DAPT following PCI for ACS remains
inconclusive.3-5, 17 Observational evidence does suggest that non-adherence to DAPT during the
early post-PCI period is associated with an increased risk of adverse cardiovascular events,
including stent thrombosis.6, 7 However, recent studies have demonstrated that the actual
minimum duration of DAPT required to reliably ensure the viability of a newly deployed stent
may be shorter than previously estimated, and significantly shorter than the guideline
recommended duration of 12 months following PCI.3, 9-11 The effect of shorter duration of DAPT
in patients undergoing PCI in the context of ACS is uncertain, as the derived benefit may not
relate to the viability of a recently deployed stent. Two recent large randomized controlled trials
suggest that prolonged DAPT following PCI, including patients post-ACS, reduces the incidence
of stent thrombosis but increases bleeding; hence, the net clinical benefit of prolonged DAPT
remains an area of active research and debate.12, 18 In real-world practice, a prolonged duration of
DAPT may be constrained by side effects, bleeding risks (particularly in patients with an
indication for OAC), financial limitations, and complications of polypharmacy (including nonadherence).8, 19-21 In addition, with the advent of newer generation stents, the rates of stent
thrombosis and other ischemic events have decreased significantly; thus, previous
recommendations regarding the optimal duration of DAPT following PCI may need to be
revisited.22, 23
In our contemporary cohort of AMI patients undergoing PCI, 1 in 4 discontinued DAPT
before the guideline recommended duration of 12 months. Most importantly, in the vast majority
of cases, DAPT was discontinued due to physician preference, rather than as a result of adverse
12
events, need for surgery, or use of OAC. The proportion of physicians discontinuing DAPT due
to the perception that it was no longer needed rose sharply after 6 months of DAPT – from 28%
to 64% when discontinuation was <6 weeks versus 6 to 12 months following PCI, respectively.
These findings support the notion that there may be significant uncertainty among practicing
physicians regarding the recommended and/or optimal duration of DAPT following myocardial
infarction and PCI. Perceived lack of supporting evidence or clinical need for guidelinerecommended practices by treating physicians has been previously identified as one of the most
common reasons for not prescribing evidence-based therapies.24 Our analysis corroborated the
findings of previous observational studies demonstrating an inverse correlation between DAPT
duration and adverse cardiovascular events.6, 7 However, patients in whom DAPT was
discontinued early represented a higher risk population at baseline; the exact effect of this bias
on the differential rates of adverse events is difficult to ascertain. Interestingly, while the inverse
correlation between adverse cardiovascular events and DAPT duration persisted across DAPT
duration strata, the rate of stent thrombosis did not differ significantly as long as DAPT duration
was ≥ 6 weeks. After this treatment period, the observed association between early DAPT
discontinuation and increased adverse events may not relate to the viability of a newly deployed
stent. After adjusting for potential confounders, an association between early DAPT
discontinuation and increased adverse cardiovascular events was noted in patients discontinuing
DAPT within 6 months of PCI. There was a trend towards an increased incidence of adverse
events when DAPT was discontinued between 6 to <12 months, compared to discontinuation
after ≥12 months, but it did not reach statistical significance. Although the current analysis
represents a non-randomized comparison, our results would suggest that patients undergoing PCI
for AMI in the current era benefit from completion of the guideline-recommended 12-month
13
DAPT course.1 In addition, the comparable rates of stent thrombosis when DAPT duration was
≥6 weeks support previous observations that shorter durations of DAPT are sufficient to ensure
viability of newer generation stents, and that the benefit derived from more prolonged DAPT
may not relate to complications of a recently deployed stent.3, 25-28
Limitations
The current study represents a non-randomized comparison designed to assess whether
findings of large DAPT trials are reflected in “real-world” practice. When assessing the effect of
DAPT discontinuation, patients in whom DAPT was discontinued early represent a selected
population as evidenced by differences in baseline characteristics between DAPT duration strata.
We used multivariable logistic regression and propensity score MMWS analyses to adjust for
variables potentially associated with the decision to discontinue DAPT. However, due to the
non-randomized nature of this analysis, the residual effect of these variables and other
unmeasured confounders cannot be completely corrected, and their exact effect on the observed
clinical outcomes is difficult to ascertain. In the ancillary analysis using multiple imputation,
data were assumed to be missing at random; however, the exact missing data mechanisms were
not known and the assumption of data missing at random could not be verified. When assessing
mortality and bleeding specifically, our observations are confounded by reverse causality –
where DAPT would have been discontinued following death or a bleeding event. The effect of
reverse causality is apparent in the strong inverse correlation between death and DAPT duration,
and the paradoxical inverse correlation between duration of DAPT and BARC ≥2 bleeding.
Thus, a causal relationship between early DAPT discontinuation and the incidence of these
clinical outcomes should not be inferred. When examining DAPT discontinuation, the exact
reason for early discontinuation was not provided for all patients. In addition, the specific type or
14
generation of drug-eluting stent was not recorded and might be associated with both the timing
of DAPT discontinuation and clinical outcomes. Lastly, COAPT was not designed or powered to
examine clinical outcomes in relation to DAPT duration following PCI for AMI. Despite these
limitations, the present observational study provides valuable contemporary insights into the
demographics, treatment, and outcomes of “real-world” patients treated with DAPT following
PCI for AMI.
Conclusion
In contemporary practice, the majority of patients undergoing PCI for AMI receive
DAPT for at least 12 months. However, early discontinuation of DAPT is not uncommon and
occurred in 25% of patients; more often due to physician preference rather than adverse events or
need for surgical interventions. Patients at higher baseline risk are more likely to discontinue
DAPT early, and early DAPT discontinuation is associated with increased rates of ischemic
events.
15
Acknowledgements and Funding
The study was designed by the study co-chairs (Mehta and Goodman) and the cardiovascular
medical director of the sponsor (Fisher) and funded by Eli Lilly and Company. Site management
was provided by the CHRC, a federally incorporated not-for-profit academic research
organization. Data management and analysis was undertaken by Inventive Health (Köln,
Germany) and Eli Lilly and Company. The authors were responsible for analysis and
interpretation of the data. The first author drafted the manuscript, and all authors had significant
input into content, analysis and interpretation.
Disclosures
Juan J Russo, none. Shaun G Goodman, speaker/consulting honoraria and/or research grant
support from Eli Lilly Canada, AstraZeneca, Bristol-Myers Squibb, Sanofi. Akshay Bagai,
none. Jean-Pierre Dery, speaker/consulting honoraria and/or research grant support from Eli
Lilly Canada, AstraZeneca, Astra-Zeneca, Sanofi, Bristol-Myers-Squibb, Amgen, Pfizer, Bayer,
Boehringer, Servier, Merck. Mary K Tan, none. Harold N Fisher, medical officer/salary, Eli
Lilly Canada. Xiang Zhang, salary, Eli Lilly and Company. Y Emily Zhu, salary, Eli Lilly and
Company. Robert C Welsh, speaker/consulting honoraria and research grant support from Eli
Lilly Canada, honoraria from AstraZeneca. Anthony J Della Siega, research grant support from
Eli Lilly Canada. Andre Kokis, none. Brian YL Wong, research grant support from Eli Lilly
Canada. Mark A Henderson, research grant support from Eli Lilly Canada. Sohrab
Lutchmedial, research grant support from Eli Lilly Canada. Shahar Lavi, speaker/consulting
honoraria and/or research grant support from AstraZeneca, Eli Lilly Canada. Shamir R Mehta,
speaker/consulting honoraria and/or research grant support from Eli Lilly Canada. Andrew T
Yan, none.
16
References
1.
Levine GN, Bates ER, Bittl JA, Brindis RG, Fihn SD, Fleisher LA, Granger CB, Lange RA,
Mack MJ, Mauri L, Mehran R, Mukherjee D, Newby LK, O'Gara PT, Sabatine MS, Smith PK,
and Smith SC, Jr. 2016 ACC/AHA guideline focused update on duration of dual antiplatelet
therapy in patients with coronary artery disease: A report of the American College of
Cardiology/American Heart Association task force on clinical practice guidelines: An update of
the 2011 ACCF/AHA/SCAI guideline for percutaneous coronary intervention, 2011 ACCF/AHA
guideline for coronary artery bypass graft surgery, 2012
ACC/AHA/ACP/AATS/PCNA/SCAI/STS guideline for the diagnosis and management of
patients with stable ischemic heart disease, 2013 ACCF/AHA guideline for the management of
ST-elevation myocardial infarction, 2014 AHA/ACC guideline for the management of patients
with non-ST-elevation acute coronary syndromes, and 2014 ACC/AHA guideline on
perioperative cardiovascular evaluation and management of patients undergoing noncardiac
surgery. Circulation. 2016; 133.
2.
Mehta SR, Yusuf S, Peters RJ, Bertrand ME, Lewis BS, Natarajan MK, Malmberg K, Rupprecht
H, Zhao F, Chrolavicius S, Copland I, Fox KA, and Clopidogrel in Unstable angina to prevent
Recurrent Events trial Investigators. Effects of pretreatment with clopidogrel and aspirin followed
by long-term therapy in patients undergoing percutaneous coronary intervention: The PCI-CURE
study. Lancet. 2001;358:527-533
3.
El-Hayek G, Messerli F, Bangalore S, Hong MK, Herzog E, Benjo A, and Tamis-Holland JE.
Meta-analysis of randomized clinical trials comparing short-term versus long-term dual
antiplatelet therapy following drug-eluting stents. Am J Cardiol. 2014;114:236-242
4.
Wallentin L, Becker RC, Budaj A, Cannon CP, Emanuelsson H, Held C, Horrow J, Husted S,
James S, Katus H, Mahaffey KW, Scirica BM, Skene A, Steg PG, Storey RF, Harrington RA,
17
Investigators P, Freij A, and Thorsen M. Ticagrelor versus clopidogrel in patients with acute
coronary syndromes. New Engl J Med. 2009;361:1045-1057
5.
Wiviott SD, Braunwald E, McCabe CH, Montalescot G, Ruzyllo W, Gottlieb S, Neumann F-J,
Ardissino D, De Servi S, Murphy SA, Riesmeyer J, Weerakkody G, Gibson CM, and Antman
EM. Prasugrel versus clopidogrel in patients with acute coronary syndromes. New Engl J Med.
2007;357:2001-2015
6.
Mehran R, Baber U, Steg PG, Ariti C, Weisz G, Witzenbichler B, Henry TD, Kini AS, Stuckey T,
Cohen DJ, Berger PB, Iakovou I, Dangas G, Waksman R, Antoniucci D, Sartori S, Krucoff MW,
Hermiller JB, Shawl F, Gibson CM, Chieffo A, Alu M, Moliterno DJ, Colombo A, and Pocock S.
Cessation of dual antiplatelet treatment and cardiac events after percutaneous coronary
intervention (PARIS): 2 year results from a prospective observational study. Lancet.
2013;382:1714-1722
7.
Cutlip DE, Kereiakes DJ, Mauri L, Stoler R, and Dauerman HL. Thrombotic complications
associated with early and late nonadherence to dual antiplatelet therapy. JACC Cardiovasc Interv.
2015;8:404-410
8.
Czarny MJ, Nathan AS, Yeh RW, Mauri L. Adherence to dual antiplatelet therapy after coronary
stenting: A systematic review. Clin Cardiol. 2014;37:505-513
9.
Spencer FA, Prasad M, Vandvik PO, Chetan D, Zhou Q, Guyatt G. Longer- versus shorterduration dual-antiplatelet therapy after drug-eluting stent placement: A systematic review and
meta-analysis. Ann Intern Med. 2015;163:118-126
10.
Palmerini T, Benedetto U, Bacchi-Reggiani L, Della Riva D, Biondi-Zoccai G, Feres F, Abizaid
A, Hong M-K, Kim B-K, Jang Y, Kim H-S, Park KW, Genereux P, Bhatt DL, Orlandi C, De
Servi S, Petrou M, Rapezzi C, and Stone GW. Mortality in patients treated with extended
duration dual antiplatelet therapy after drug-eluting stent implantation: A pairwise and bayesian
network meta-analysis of randomised trials. Lancet. 2015;385:2371-2382
18
11.
Montalescot G, Brieger D, Dalby AJ, Park S-J, and Mehran R. Duration of dual antiplatelet
therapy after coronary stenting: A review of the evidence. J Am Coll Cardiol. 2015;66:832-847
12.
Mauri L, Kereiakes DJ, Yeh RW, Driscoll-Shempp P, Cutlip DE, Steg PG, Normand S-LT,
Braunwald E, Wiviott SD, Cohen DJ, Holmes DR, Jr., Krucoff MW, Hermiller J, Dauerman HL,
Simon DI, Kandzari DE, Garratt KN, Lee DP, Pow TK, Ver Lee P, Rinaldi MJ, and Massaro JM.
Twelve or 30 months of dual antiplatelet therapy after drug-eluting stents. New Engl J Med.
2014;371:2155-2166
13.
Bonaca MP, Bhatt DL, Cohen M, Steg PG, Storey RF, Jensen EC, Magnani G, Bansilal S, Fish
MP, Im K, Bengtsson O, Oude Ophuis T, Budaj A, Theroux P, Ruda M, Hamm C, Goto S, Spinar
J, Nicolau JC, Kiss RG, Murphy SA, Wiviott SD, Held P, Braunwald E, and Sabatine MS. Longterm use of ticagrelor in patients with prior myocardial infarction. New Engl J Med.
2015;372:1791-1800
14.
Mehran R, Rao SV, Bhatt DL, Gibson CM, Caixeta A, Eikelboom J, Kaul S, Wiviott SD, Menon
V, Nikolsky E, Serebruany V, Valgimigli M, Vranckx P, Taggart D, Sabik JF, Cutlip DE,
Krucoff MW, Ohman EM, Steg PG, and White H. Standardized bleeding definitions for
cardiovascular clinical trials: A consensus report from the Bleeding Academic Research
Consortium. Circulation. 2011;123:2736-2747
15.
Granger CB, Goldberg RJ, Dabbous O, Pieper KS, Eagle KA, Cannon CP, Van De Werf F,
Avezum A, Goodman SG, Flather MD, and Fox KA. Predictors of hospital mortality in the
Global Registry of Acute Coronary Events. Arch Intern Med. 2003;163:2345-2353
16.
Linden A. Combining propensity score-based stratification and weighting to improve causal
inference in the evaluation of health care interventions. J Eval Clin Pract. 2014;20:1065-1071
17.
Effects of clopidogrel in addition to aspirin in patients with acute coronary syndromes without stsegment elevation. New Engl J Med. 2001;345:494-502
18.
Udell JA, Bonaca MP, Collet J-P, Lincoff AM, Kereiakes DJ, Costa F, Lee CW, Mauri L,
Valgimigli M, Park S-J, Montalescot G, Sabatine MS, Braunwald E, and Bhatt DL. Long-term
19
dual antiplatelet therapy for secondary prevention of cardiovascular events in the subgroup of
patients with previous myocardial infarction: A collaborative meta-analysis of randomized trials.
Eur Heart J. 2015
19.
Quadros AS, Welter DI, Camozzatto FO, Chaves A, Mehta RH, Gottschall CA, and Lopes RD.
Identifying patients at risk for premature discontinuation of thienopyridine after coronary stent
implantation. Am J Cardiol. 2011;107:685-689
20.
Ko DT, Chiu M, Guo H, Austin PC, Marquis J-F, and Tu JV. Patterns of use of thienopyridine
therapy after percutaneous coronary interventions with drug-eluting stents and bare-metal stents.
Am Heart J. 2009;158:592-598.e591
21.
Ferreira-Gonzalez I, Marsal JR, Ribera A, Permanyer-Miralda G, Garcia-Del Blanco B, Marti G,
Cascant P, Martin-Yuste V, Brugaletta S, Sabate M, Alfonso F, Capote ML, De La Torre JM,
Ruiz-Lera M, Sanmiguel D, Cardenas M, Pujol B, Baz JA, Iniguez A, Trillo R, Gonzalez-Bejar
O, Casanova J, Sanchez-Gila J, and Garcia-Dorado D. Background, incidence, and predictors of
antiplatelet therapy discontinuation during the first year after drug-eluting stent implantation.
Circulation. 2010;122:1017-1025
22.
Camenzind E, Boersma E, Wijns W, Mauri L, Rademaker-Havinga T, Ordoubadi FF, Suttorp MJ,
Al Kurdi M, and Steg PG. Modifying effect of dual antiplatelet therapy on incidence of stent
thrombosis according to implanted drug-eluting stent type. Eur Heart J. 2014;35:1932-1948
23.
Naidu SS, Krucoff MW, Rutledge DR, Mao VW, Zhao W, Zheng Q, Wilburn O, Sudhir K,
Simonton C, Hermiller JB. Contemporary incidence and predictors of stent thrombosis and other
major adverse cardiac events in the year after XIENCE V implantation: Results from the 8,061patient XIENCE V united states study. JACC Cardiovasc Interv. 2012;5:626-635
24.
Bagnall AJ, Yan AT, Yan RT, Lee CH, Tan M, Baer C, Polasek P, Fitchett DH, Langer A,
Goodman SG, Canadian Acute Coronary Syndromes Registry III. Optimal medical therapy for
non-ST-segment-elevation acute coronary syndromes: Exploring why physicians do not prescribe
20
evidence-based treatment and why patients discontinue medications after discharge. Circ
Cardiovasc Qual Outcomes. 2010;3:530-537
25.
Gwon H-C, Hahn J-Y, Park KW, Song YB, Chae I-H, Lim D-S, Han K-R, Choi J-H, Choi S-H,
Kang H-J, Koo B-K, Ahn T, Yoon J-H, Jeong M-H, Hong T-J, Chung W-Y, Choi Y-J, Hur S-H,
Kwon H-M, Jeon D-W, Kim B-O, Park S-H, Lee N-H, Jeon H-K, Jang Y, Kim H-S. Six-month
versus 12-month dual antiplatelet therapy after implantation of drug-eluting stents: The efficacy
of XIENCE/PROMUS versus CYPHER to reduce late loss after stenting (EXCELLENT)
randomized, multicenter study. Circulation. 2012;125:505-513
26.
Kim B-K, Hong M-K, Shin D-H, Nam C-M, Kim J-S, Ko Y-G, Choi D, Kang T-S, Park B-E,
Kang W-C, Lee S-H, Yoon J-H, Hong B-K, Kwon H-M, and Jang Y. A new strategy for
discontinuation of dual antiplatelet therapy: The RESET trial (REal Safety and Efficacy of 3month dual antiplatelet Therapy following Endeavor zotarolimus-eluting stent implantation). J
Am Coll Cardiol. 2012;60:1340-1348
27.
Valgimigli M, Campo G, Monti M, Vranckx P, Percoco G, Tumscitz C, Castriota F, Colombo F,
Tebaldi M, Fuca G, Kubbajeh Md, Cangiano E, Minarelli M, Scalone A, Cavazza C, Frangione
A, Borghesi M, Marchesini J, Parrinello G, Ferrari R, Prolonging Dual Antiplatelet Treatment
After Grading Stent-Induced Intimal Hyperplasia Study Investigators. Short- versus long-term
duration of dual-antiplatelet therapy after coronary stenting: A randomized multicenter trial.
Circulation. 2012;125:2015-2026
28.
Feres F, Costa RA, Abizaid A, Leon MB, Marin-Neto JA, Botelho RV, King SB, 3rd, Negoita M,
Liu M, de Paula JET, Mangione JA, Meireles GX, Castello HJ, Jr., Nicolela EL, Jr., Perin MA,
Devito FS, Labrunie A, Salvadori D, Jr., Gusmao M, Staico R, Costa JR, Jr., de Castro JP,
Abizaid AS, and Bhatt DL. Three vs twelve months of dual antiplatelet therapy after zotarolimuseluting stents: The OPTIMIZE randomized trial. JAMA. 2013;310:2510-2522
21
Table 1. Baseline patient characteristics
6 to <12
months
(n=256)
≥12 months
(n=105)
6 weeks to
<6 months
(n=142)
62.5 (55-71)
64.5 (54-73)
60 (54-68)
60 (53-67)
<0.001
28 (27)
30 (21)
50 (20)
322 (21)
0.39
81 (71-95)
84 (72-94)
82(74-93)
84 (75-96)
0.02
Hypertension– n(%)
70 (67)
76 (54)
113 (44)
755 (49)
0.01
Diabetes mellitus– n(%)
25 (24)
30 (21)
43 (17)
277 (18)
0.16
Dyslipidemia– n(%)
62 (59)
71 (50)
113 (44)
698 (46)
0.02
History of smoking– n(%)
72 (75)
84 (68)
156 (70)
943 (71)
0.93
Current smoker– n(%)
33 (34)
45 (36)
79 (35)
494 (37)
0.48
Prior MI– n(%)
47 (45)
74 (52)
77 (30)
489 (32)
<0.001
Prior heart failure– n(%)
5 (4.8)
10 (7.0)
3 (1.2)
25 (1.6)
<0.001
Prior stroke or TIA– n(%)
8 (7.6)
8 (5.6)
8 (3.1)
48 (3.1)
0.01
Prior peripheral arterial
disease– n(%)
5 (4.8)
4 (2.8)
4 (1.6)
59 (3.9)
0.64
Prior PCI– n(%)
34 (32)
57 (40)
62 (24)
395 (26)
0.004
Prior CABG– n(%)
13 (12)
10 (7.0)
14 (5.5)
71 (4.6)
0.001
Prior GI bleed– n(%)
0 (0.0)
2 (1.4)
2 (0.8)
9 (0.6)
0.87
Atrial fibrillation– n(%)
13 (12)
12 (8.5)
7 (2.7)
31 (2.0)
<0.001
Creatinine (umol/L)–a
85 (74-99)
89 (75-110)
83 (71-98)
82 (70-95)
0.006
GRACE risk score–a
138 (113-158)
145 (111170)
127 (108-154)
127 (108146)
<0.001
Characteristic
Age (years)–a
Female sex– n(%)
Weight (kg)–a
a
<6 weeks
median (25th,75th percentiles); OAC=oral anticoagulant.
p value
(trend)
(n=1531)
22
CABG=coronary artery bypass grafting; GI=gastrointestinal; GRACE=Global Registry of Acute
Coronary Events; MI=myocardial infarction; PCI=percutaneous coronary intervention; TIA=transient
ischemic attack.
23
Table 2. Index cardiac event and treatment characteristics
Characteristic
STEMI— n(%)
6 to <12
months
(n=256)
≥12 months
(n=105)
6 weeks to
<6 months
(n=142)
66 (63)
86 (61)
176 (69)
939 (61)
<6 weeks
(n=1531)
Killip class— n(%)
77 (93)
103 (88)
192 (94)
1109 (94)
II
3 (3.6)
8 (6.8)
6 (2.9)
42 (3.6)
III
2 (2.4)
5 (4.3)
3 (1.5)
15 (1.3)
IV
1 (1.2)
1 (0.9)
3 (1.5)
13 (1.1)
4 (3.8)
13 (9.2)
11 (4.3)
73 (4.8)
Access site— n(%)
73 (70)
109 (77)
183 (72)
1067 (70)
Femoral artery
32 (31)
33 (23)
70 (27)
452 (30)
Brachial artery
0 (0.0)
0 (0.0)
3 (1.2)
10 (0.7)
Infarct-related artery— n(%)
0.04
Left main
2 (2.2)
6 (5.0)
4 (1.8)
21 (1.6)
Left anterior descending artery
40 (44)
50 (41)
83 (36)
540 (41)
Left circumflex
20 (22)
24 (20)
33 (15)
248 (19)
Right coronary artery
28 (31)
41 (34)
108 (47)
514 (39)
Baseline IRA TIMI flow– n(%)
0.48
0
35 (43)
33 (30)
86 (41)
441 (36)
1
6 (7.3)
16 (15)
21 (10)
158 (13)
2
11 (13)
22 (20)
35 (17)
211 (17)
3
30 (37)
39 (36)
66 (32)
409 (34)
29 (32)
39 (32)
102 (45)
730 (55)
Discharge ADP– n(%)
0.11
0.45
Radial artery
Drug Eluting Stent– n(%)a
0.16
0.30
I
Cardiac arrest— n(%)
p value
<0.001
0.17
24
Clopidogrel
81 (77)
107 (75)
173 (68)
1111 (73)
Ticagrelor
16 (15)
25 (18)
57 (22)
250 (16)
Prasugrel
8 (7.6)
10 (7.0)
26 (10)
170 (11)
25 (24)
31 (22)
38 (15)
183 (12)
Adverse event
3 (5.2)
10 (14)
10 (5.2)
6 (0.9)
Need for OAC
5 (8.6)
3 (4.1)
0 (0)
1 (0.1)
Need for surgery
3 (5.2)
4 (5.5)
1 (0.5)
1 (0.1)
Patient decision
1 (1.7)
2 (2.7)
7 (3.6)
4 (0.6)
0 (0)
3 (4.1)
1 (0.5)
0 (0)
DAPT deemed no longer
needed
16 (27.6)
20 (27.4)
125 (64.4)
553 (80.9)
Other physician decision
20 (34.5)
27 (37.0)
49 (25.3)
113 (16.5)
Other
10 (17.2)
4 (5.5)
1 (0.5)
6 (0.9)
OAC on discharge– n(%)
<0.001
Reason for DAPT
discontinuation– n(%)b
Financial limitations
a
Data on stent type available for 1761 of 2034 patients (86.6%).
b
Not mutually exclusive; no specific reason for early DAPT discontinuation provided for 178 patients
(35%).
ADP=adenosine diphosphate; DAPT=dual antiplatelet therapy; IRA=infarct-related artery; OAC=oral
anticoagulation; STEMI=ST-elevation myocardial infarction, TIMI=Thrombolysis in Myocardial
Infarction.
Table 3. Unadjusted outcomes stratified by timing of discontinuation
25
Clinical Outcomes
at 15 months
All
patients
<6 weeks
6 weeks to
<6 months
6 to 12
months
>12 months
(2034)
(n=105)
(n=142)
(n=256)
(n=1531)
Composite cardiovascular
outcome– n(%)
337 (17)
35 (33)
40 (28)
47 (18)
215 (14)
<0.001
Myocardial infarction–
n(%)
191 (9.4)
18 (17)
18 (13)
32 (13)
123 (8.0)
<0.001
Stent thrombosis– n(%)
32 (1.6)
6 (5.7)
1 (0.7)
4 (1.6)
21 (1.4)
0.03
Unplanned coronary
revascularization– n(%)
164 (8.1)
12 (11)
16 (11)
25 (9.8)
111 (7.3)
0.02
New or worsening heart
failure– n(%)
107 (5.3)
17 (16)
16 (11)
13 (5.1)
61 (4.0)
<0.001
Cardiogenic shock– n(%)
29 (1.4)
6 (5.7)
4 (2.8)
2 (0.8)
17 (1.1)
0.001
Stroke or TIA– n(%)
18 (0.9)
2 (1.9)
3 (2.1)
1 (0.4)
12 (0.8)
0.15
Death– n(%)
50 (2.5)
22 (21)
15 (11)
8 (3.1)
5 (0.3)
<0.001
Bleeding event– n(%)
515 (25.3)
29 (28)
41 (29)
72 (28)
373 (24)
0.13
BARC≥2 bleeding– n(%)
120 (5.9)
9 (8.6)
17 (12)
17 (6.6)
77 (5.0_
<0.001
Any transfusion– n(%)
31 (1.5)
2 (1.9)
4 (2.8)
6 (2.3)
19 (1.2)
0.15
BARC=Bleeding Academic Research Consortium; TIA=transient ischemic attack.
p value
(trend)
26
Table 4. Adjusted composite cardiovascular outcome in relation to DAPT duration after propensity score matching and propensity score marginal
mean weighting through stratification with doubly robust model
Variable
Forest plot
OR (95% CI)
p value
<6 weeks
2.56 (1.64 – 4.00)
<0.0001
6 weeks to <6 months
1.95 (1.28 – 2.97)
0.002
6 months to <12 months
1.37 (0.96 – 1.95)
0.08
2.80 (1.74 - 4.49)
<0.0001
1.93 (1.25 – 3.00)
0.003
1.37 (0.95 – 1.98)
0.09
DAPT duration (reference group: ≥12 months)
Propensity score MMWS only model
Doubly robust model
<6 weeks
6 weeks to <6 months
6 months to <12 months
DAPT=dual antiplatelet therapy; MMWS=marginal mean weighting through stratification.
27
28
Supplementary Table 1. Adjusted odds ratio for composite cardiovascular outcome after propensity
score marginal mean weighting through stratification in the doubly robust model
Variables
Adjusted OR
p value
(95% CI)
DAPT duration
<6 weeks
2.80 (1.74-4.49)
<0.0001
6 weeks to <6 months
1.93 (1.25-3.00)
0.003
6 to <12 months
1.37 (0.95-1.98)
0.09
≥12 months
1.00 (reference)
Age (years)a
1.04 (0.92-1.18)
0.48
Systolic BP (mmHg)a
1.00 (0.95-1.04)
0.90
Heart rate (beats/min)a
1.09 (1.02-1.16)
0.01
STEMI (compared to NSTEMI)
1.19 (0.90-1.58)
0.21
Cardiac arrest on presentation
1.50 (0.87-2.59)
0.15
OAC on discharge
2.71 (1.98-3.70)
<0.0001
Myocardial infarction
2.11 (1.48-3.00)
<0.0001
Percutaneous coronary intervention
1.19 (0.83-1.71)
0.35
Coronary artery bypass grafting
1.53 (0.92-2.53)
0.10
Heart failure
2.70 (1.34-5.45)
0.006
Stroke or transient ischemic attack
2.29 (1.32-3.99)
0.003
Atrial fibrillation
0.53 (0.26-1.11)
0.09
Dyslipidemia
0.74 (0.56-1.00)
0.03
Hypertension
1.05 (0.79-1.40)
0.72
Previous medical history
a
OR per 10 unit increase. BP=blood pressure; DAPT=dual antiplatelet therapy; NSTEMI=non ST-
elevation myocardial infarction; OAC=oral anticoagulation; OR=odds ratio; STEMI=ST-elevation
myocardial infarction.
29
Supplementary Table 2. Adjusted and unadjusted composite cardiovascular outcome (random intercept model)
Clinical outcome
Duration of DAPT
Unadjusted OR
p value
(95% CI)
Composite
cardiovascular
outcome
Adjusted ORa
p value
(95% CI)
<6 weeks
3.28 (2.02-5.35)
<0.001
2.40 (1.41-4.08)
0.001
6 weeks to <6 months
2.23 (1.39-3.57)
<0.001
1.60 (0.95-2.69)
0.07
6 to <12 months
1.12 (0.72-1.76)
0.62
1.16 (0.72-1.87)
0.54
≥12 months
1.00 (reference)
1.00 (reference)
a
Adjusted for age, systolic blood pressure, heart rate, type of myocardial infarction (STEMI versus NSTEMI), oral anticoagulant
(OAC) therapy on discharge, cardiac arrest on presentation, and previous history of myocardial infarction, PCI, heart failure, stroke or
transient ischemic attack, atrial fibrillation, coronary artery bypass grafting, hypertension, and dyslipidemia.
DAPT=dual antiplatelet therapy; OR=odds ratio.
30
Supplementary Table 3. Multivariable logistic regression analysis for the composite cardiovascular outcome (multiple imputation model)
Variable
Forest plot
OR (95% CI)
p value
<6 weeks
2.50 (1.59-3.91)
<0.0001
6 weeks to <6 months
1.77 (1.17-2.68)
0.007
6 months to <12 months
1.38 (0.97-1.98)
0.08
GRACE risk score (per 10 points higher)
1.05 (1.01-1.105)
0.02
NSTEMI (Reference group: STEMI)
0.93 (0.71-1.22)
0.61
OAC on discharge
2.56 (1.89-3.47)
<0.0001
Newer ADP receptor antagonist
0.69 (0.52-0.93)
0.01
Previous MI, PCI, or CABG
2.31 (1.80-2.96)
< 0.0001
DAPT duration (reference group: ≥12 months)
CABG=coronary artery bypass grafting; DAPT=dual antiplatelet therapy; GRACE=Global Registry of Acute Coronary Events; MI=myocardial
infarction; NSTEMI=non ST-elevation myocardial infarction; OAC=oral anticoagulation; OR=odds ratio; PCI=percutaneous coronary
intervention; STEMI=ST-elevation myocardial infarction.