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Evaluation of Prolonged Antithrombotic Pretreatment ("Cooling-Off" Strategy) Before Intervention in Patients With Unstable Coronary Syndromes
A Randomized Controlled Trial
Franz-Josef Neumann, MD;
Adnan Kastrati, MD;
Gisela Pogatsa-Murray, MD;
Julinda Mehilli, MD;
Hildegard Bollwein, MD;
Hans-Peter Bestehorn, MD;
Claus Schmitt, MD;
Melchior Seyfarth, MD;
Josef Dirschinger, MD;
Albert Schömig, MD
JAMA. 2003;290:1593-1599.
ABSTRACT
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Context In unstable coronary syndromes, catheter intervention is frequently preceded by antithrombotic treatment to reduce periprocedural risk; however, evidence from clinical trials to support antithrombotic pretreatment is sparse.
Objective To test the hypothesis that prolonged antithrombotic pretreatment improves the outcome of catheter intervention in patients with acute unstable coronary syndromes compared with early intervention.
Design, Setting, and Patients Randomized controlled trial conducted from February 27, 2000, to April 8, 2002, and including patients admitted to 2 German tertiary care centers with symptoms of unstable angina plus either ST-segment depression or elevation of cardiac troponin T levels.
Interventions Patients were randomly allocated to antithrombotic pretreatment for 3 to 5 days or to early intervention after pretreatment for less than 6 hours. In both groups, antithrombotic pretreatment consisted of intravenous unfractionated heparin (60-U/kg bolus followed by infusion adjusted to maintain partial thromboplastin time of 60 to 85 seconds), aspirin (500-mg intravenous bolus followed by 100-mg twice-daily oral dose), oral clopidogrel (600-mg loading dose followed by 75-mg twice-daily dose), and intravenous tirofiban (10-µg/kg bolus followed by continuous infusion of 0.10 µg/kg per min).
Main Outcome Measure Composite 30-day incidence of large nonfatal myocardial infarction or death from any cause.
Results Of the 410 patients enrolled, 207 were allocated to receive prolonged antithrombotic pretreatment and 203 to receive early intervention. Elevated levels of cardiac troponin T were present in 274 patients (67%), while 268 (65%) had ST-segment depression. The antithrombotic pretreatment and the early intervention groups were well matched with respect to major baseline characteristics and definitive treatment (catheter revascularization: 133 [64.3%] vs 143 [70.4%], respectively; coronary artery bypass graft surgery: 16 [7.7%] vs 16 [7.9%]). The primary end point was reached in 11.6% (3 deaths, 21 infarctions) of the group receiving prolonged antithrombotic pretreatment and in 5.9% (no deaths, 12 infarctions) of the group receiving early intervention (relative risk, 1.96 [95% confidence interval, 1.01-3.82]; P = .04). This outcome was attributable to events occurring before catheterization; after catheterization, both groups incurred 11 events each (P = .92).
Conclusion In patients with unstable coronary syndromes, deferral of intervention for prolonged antithrombotic pretreatment does not improve the outcome compared with immediate intervention accompanied by intense antiplatelet treatment.
INTRODUCTION
The best treatment option for most patients with unstable coronary syndromes is angiographically guided revascularization, irrespective of the primary success of medical treatment.1-4 Compared with a conservative strategy that reserves coronary angiography for persisting spontaneous or inducible ischemia, an invasive strategy reduces risk of adverse events including large myocardial infarction (MI),1-3 severe recurrent angina,4 and death.2 This has been shown for patients with non–ST-segment elevation MI and for those with unstable angina and ST-segment depression.1-4
The risk associated with percutaneous coronary intervention as well as that of coronary artery bypass graft (CABG) surgery is, however, increased in patients with unstable coronary syndromes.5-8 To minimize this hazard, some have recommended passivating the plaque activity by means of extended antithrombotic treatment before intervention.9 Several observational studies comparing swift intervention vs antithrombotic pretreatment for unstable coronary syndromes have found a lower rate of complications in patients undergoing percutaneous intervention after more than 48 hours of antithrombotic pretreatment.10-12 Pursuing such a "cooling-off" strategy, investigators in the second Fast Revascularization during Instability in Coronary Artery Disease (FRISC II) trial1 incorporated a 4-day medical stabilization period preceding intervention into the FRISC II protocol and speculated that this prolonged treatment period was a prerequisite for the substantial benefit of the invasive strategy. Other trials have demonstrated a reduction in intracoronary thrombus burden by prolonged pretreatment with glycoprotein IIb/IIIa inhibitors.13-14 Nevertheless, evidence in support of prolonged antithrombotic pretreatment is still largely observational, and potent platelet inhibition at the time of intervention only may suffice to optimize the outcome with early revascularization.15-17 In the absence of dedicated clinical trials, current guidelines are equivocal as to the optimal timing of intervention in unstable coronary syndromes.12, 18
To test the hypothesis that prolonged antithrombotic pretreatment is beneficial before catheter intervention in patients with unstable coronary syndromes, we conducted the Intracoronary Stenting With Antithrombotic Regimen Cooling-Off (ISAR-COOL) trial.
METHODS
Patients
Our trial included patients with angina pectoris at rest or with minimal exertion, with the last episode occurring 24 hours or less before study entry. Myocardial ischemia had to be verified by horizontal or downsloping ST-segment depression of 0.1 mV or greater and/or cardiac troponin T concentration of 0.03 mg/L or greater (Roche Cardiac reader system, Roche-Boehringer-Mannheim, Mannheim, Germany). We excluded patients with evidence of large myocardial infarction, including ST-segment elevation of at least 1 mV in 2 or more contiguous leads or elevation of the catalytic activity of creatine kinase and its MB isoenzyme to 3 times the upper limit of normal or greater; those with hemodynamic instability; those with contraindications to study medication; or those unable to provide written informed consent for participation. The study was approved by the ethics committee of the medical faculty of the Technische Universität of Munich.
Randomization and Interventions
The trial was conducted at 2 German tertiary care centers. Allocation to early intervention or prolonged antithrombotic pretreatment was made by means of sealed envelopes containing a concealed computer-generated random sequence, which was set in blocks of 50 for each of the participating hospitals. The size of the block was preselected by the statistician and was unknown to the investigators and medical staff caring for the patients. Dedicated medical staff performed randomization and assigned participants to their groups immediately after establishing eligibility and obtaining written informed consent. Eligible patients were randomized to each of the 2 treatment groups in equal proportions and in the order that they qualified. The 2 treatment groups were studied concurrently. Time zero was defined as the time of randomization.
With the early intervention strategy we performed coronary angiography as soon as possible, at least within 6 hours, during which time antithrombotic pretreatment was instituted. With the prolonged antithrombotic pretreatment strategy, we continued pretreatment for at least 3 days, to a maximum of 5 days, after which all patients underwent coronary angiography. Patients assigned to the prolonged antithrombotic pretreatment strategy could undergo immediate intervention for severe refractory angina, hemodynamic instability, or when they reached the primary end point (see below). In both groups, our goal was immediate revascularization after coronary angiography, preferably by ad hoc percutaneous catheter intervention.
Apart from duration, antithrombotic pretreatment was identical in both study groups and was started immediately after randomization. Antithrombotic pretreatment consisted of (1) unfractionated heparin, initial bolus of 60 U/kg followed by infusion adjusted to a partial thromboplastin time of 60 to 85 seconds; (2) aspirin, initial intravenous bolus of 500 mg followed by 100-mg tablets twice daily; (3) oral clopidogrel, initial loading dose of 600 mg followed by 75 mg twice daily19; and (4) intravenous tirofiban, initial bolus of 10 µg/kg followed by continuous infusion of 0.10 µg/kg per minute.3 As soon as the decision was made to implement percutaneous catheter intervention, we administered an additional bolus of 60 U/kg of heparin and adjusted the infusion rate of tirofiban to 0.15 µg/kg per minute.20 We continued tirofiban for 24 hours and clopidogrel for 4 weeks after the intervention. At day 4 after catheter intervention, we reduced the dose of clopidogrel to 75 mg once daily. In patients assigned to conservative treatment (ie, medical treatment alone) or to CABG surgery, we stopped clopidogrel and tirofiban after catheterization; heparin could be continued until surgery if indicated clinically. For both groups, the study protocol mandated  -blockers, angiotensin-converting enzyme inhibitors, and statins as concomitant treatment. Nitrates were allowed if needed for suppression of angina.
We analyzed biochemical markers of myocardial damage every 8 hours before catheterization and up to 48 hours after surgical or percutaneous catheter revascularization. Thereafter and in patients treated conservatively after catheterization, myocardial marker proteins were analyzed daily and for new episodes of severe chest pain until hospital discharge. Patients underwent conventional 12-lead electrocardiography on admission, immediately after revascularization, and at least once daily thereafter, until hospital discharge. We performed a telephone interview at 30 days. For patients reporting cardiac symptoms, at least 1 clinical and electrocardiographic examination was performed in the outpatient clinic or by the referring physician. Thirty-day follow-up was complete in all surviving patients; in addition, 330 patients (80.5%) subsequently had direct visits to our institutions. All information derived from contingent hospital readmission records or provided by the referring physician or by the outpatient clinic was entered into a computer database.
Outcomes
Our primary end point was the combined cumulative incidence of large MI or death from any cause during 30 days of follow-up. Large MI was defined by the occurence of any of the following: new Q waves in 2 or more contiguous electrocardiographic leads, new left bundle branch block, or elevation of the catalytic activity of creatine kinase and its MB isoenzyme to at least 5 times the upper limit of normal. After CABG surgery, we diagnosed large MI if the catalytic activity of creatinine kinase MB isoenzyme exceeded 30 U/L.
In addition, we assessed bleeding complications. According to the Thrombolysis in Myocarcardial Infarction (TIMI) trial definitions,3 a bleeding event was defined as major if it was intracranial or if there were clinically significant overt signs of hemorrhage associated with a drop in hemoglobin of more than 5 g/dL. To account for transfusion, an increase of 1 g/dL in hemoglobin was assumed for each unit of blood. All end points were adjudicated by an independent blinded committee.
Statistical Methods
For calculation of sample size, we assumed a 7% 30-day incidence of death and MI with prolonged antithrombotic pretreatment and hypothesized that this represented a 60% relative risk reduction compared with early intervention. We designed the study to have a power of 80% to test this hypothesis, with a 2-sided P value of less than .05 indicating statistical significance. According to these assumptions, 203 patients were required in each treatment group. In a prespecified secondary analysis, we compared the incidence of our primary end point after catheterization between the 2 treatment strategies. According to the intention-to-treat principle, all primary analyses were based on data from all patients as randomized.
Continuous variables are presented as median (interquartile range). We report categorical variables as counts and proportions and assessed differences between the groups with use of a 2-sided  2 test or Fisher exact test as appropriate. In addition, we report our primary end point as an information-preserving composite end point.21 We analyzed survival by the Kaplan-Meier method. We calculated a multivariate logistic regression model adjusting for age, sex, smoking, serum cholesterol level, hypertension, diabetes, insulin-dependent diabetes, prior angioplasty, prior CABG surgery, prior MI, ST-segment depression, cardiac troponin T level, coronary stenosis of 50% or greater, and left ventricular ejection fraction. Some of the relative risks and 95% confidence intervals (CIs) were calculated by conventional methods included in the crosstabs procedure of SPSS version 11.5 (SPSS Inc, Chicago, Ill). We also used S-Plus version 4.5 (Insightful Corp, Seattle, Wash) for statistical analyses.
RESULTS
The trial profile is shown in Figure 1. From February 27, 2000, until April 8, 2002, we enrolled 410 patients, of whom 207 were allocated to receive prolonged antithrombotic pretreatment and 203 to receive early intervention. There were no significant differences between the study groups with respect to entry criteria and other baseline characteristics (Table 1). Elevated levels of cardiac troponin T were present in 274 patients (67%) while 268 (65%) had ST-segment depression. In both groups, half of the patients were aged 70 years and older, and one third (136/410) were women. Patients with diabetes mellitus constituted 29% (118/410) of our study cohort.
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Table 1. Baseline Demographic, Clinical, and Angiographic Characteristics of the Study Cohort
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The median time to catheterization with prolonged antithrombotic pretreatment was 86 hours; we catheterized only 12 patients in this group (5.8%) prematurely according to the prespecified criteria. Of the patients assigned to early intervention, 87.2% (177/203) underwent coronary angiography within 6 hours, while the median time to catheterization was only 2.4 hours (Figure 2).
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Figure 2. Time to Catheterization
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The angiographic baseline characteristics were not significantly different between the 2 treatment groups (Table 1). More than two thirds (69.5% [285]) of our patient population had multivessel disease and 89% (364) had coronary artery stenosis of 50% or greater. The definitive treatment did not differ significantly between the antithrombotic pretreatment and the early intervention groups (catheter revascularization: 133 [64.3%] vs 143 [70.4%]; CABG surgery: 16 [7.7%] vs 16 [7.9%]), nor did concomitant medication (Table 2). We did not use drug-eluting stents, atherectomy, or brachytherapy.
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Table 2. Definitive Treatment and Concomitant Therapy
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At 30 days, the cumulative incidence of large MI or death from any cause differed significantly between the 2 treatment strategies (Figure 3); this combined end point was reached in 11.6% (3 deaths, 21 infarctions) of the antithrombotic pretreatment group and in 5.9% (no deaths, 12 infarctions) of the early intervention group (relative risk [95% CI], 1.96 [1.01-3.82]; P = .04 [Fisher exact test, P = .05]). The observed incidences of both death and MI tended to be higher with prolonged antithrombotic pretreatment as compared with early intervention when we analyzed each component of the primary end point separately (Table 3). If we present our primary end point in an information-preserving form, the number of patients in each of 3 categories (death, nonfatal MI, neither event) was 3, 21, and 183, respectively, in the antithrombotic pretreatment group and 0, 12, and 191, respectively, in the early intervention group.
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Figure 3. Cumulative Incidence of Death and Myocardial Infarction at 30 Days
P value is from unadjusted 2 test.
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Table 3. Incidence of Clinical Events During 30 Days
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In a multivariable logistic regression model that took into account baseline variables listed in Table 1, the adjusted odds ratio (OR) was 2.17 (95% CI, 1.01-4.76) (P = .047) for the primary end point comparing the prolonged antithrombotic pretreatment strategy with the early intervention strategy. This was similar to the unadjusted OR of 2.09 (95% CI, 1.01-4.30) (P = .046) for the primary end point comparing prolonged antithriombotic pretreatment with early intervention.
Findings in subgroups defined by entry criteria or definite treatment were consistent with the main study results. We found no significant effect on our primary end point when comparing prolonged antithrombotic pretreatment vs early intervention, either in patients with elevated levels of cardiac troponin T (OR, 1.65 [95% CI, 0.75-3.64]) or in those with ST-segment depression (OR, 1.50 [95% CI, 0.67-3.37]). Similarly, in patients undergoing percutaneous catheter intervention there was no detectable benefit of prolonged antithrombotic pretreatment compared with early intervention (OR, 1.64 [95% CI, 0.73-3.68]).
Irrespective of the duration of pretreatment, the event rate after catheterization was similar in both study groups (P = .92), with 11 events occurring in each of the 2 treatment groups (Figure 4). In the early intervention group only 1 event occurred before catheterization, whereas the longer duration of pretreatment in the prolonged antithrombotic pretreatment group resulted in 13 precatheterization events. Major bleeding and severe thrombocytopenia occurred at a similar rate in both groups (Table 3). None of our patients experienced cerebral hemorrhage.
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Figure 4. Cumulative Incidence of Death and Myocardial Infarction at 30 Days After Catheterization
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COMMENT
In our randomized controlled trial in patients with unstable coronary syndromes, deferral of intervention for prolonged antithrombotic pretreatment did not improve outcome compared with immediate intervention accompanied by intense antiplatelet treatment. On the contrary, we observed a significant increase in the cumulative 30-day incidence of large MI or death from any cause in patients who underwent prolonged antithrombotic pretreatment. The cardiac event rate after catheterization was almost identical irrespective of the duration of antithrombotic pretreatment. The intense antithrombotic treatment including triple antiplatelet therapy at the time of catheter intervention may have contributed substantially to outcome after catheterization. Without this antiplatelet regimen the prevention of excessive peri-interventional MIs in the early intervention group might not have occurred.
In trials on the peri-interventional use of abciximab, the excessive risk of catheter intervention in unstable coronary syndromes was reduced to close to that observed among patients with stable angina.15-17 Thus, abciximab administered at the time of intervention appeared to achieve plaque passivation.22 In our study, the high loading dose of clopidogrel in combination with tirofiban afforded even stronger platelet inhibition at the time of intervention.19 Whereas earlier trials used the 300-mg loading dose of clopidogrel, the 600-mg loading dose used in the ISAR-COOL trial had been tested in 2 more recent studies—a large registry23 as well as the ISAR-REACT (Intracoronary Stenting and Antithrombotic Regimen–Rapid Early Action For Coronary Treatment) trial.24 The ISAR-REACT trial addressed peri-interventional antithrombotic therapy in patients without myocardial marker proteins or ischemic ST-segment changes. In the low to intermediate–risk cohort of the ISAR-REACT trial, clopidogrel alone with a 600-mg loading dose was highly effective because abciximab was no longer needed to reduce the risk of peri-interventional ischemic events. With a 600-mg loading dose, a 2-hour delay, as in the early intervention group, suffices to achieve an almost full effect of adenosine diphosphate–receptor inhibition.19 Within the same time frame, tirofiban would have achieved a steady-state concentration that enables a robust potent antiaggregatory effect.25 Our study shows that the plaque passivation achieved by such intense antiplatelet therapy at the time of intervention cannot be surpassed by extended pretreatment; ie, extended pretreatment does not improve outcome.
Compared with the early intervention strategy, the excessive event rate with the antithrombotic pretreatment strategy was incurred exclusively during pretreatment, presumably as a consequence of its differential duration. During the pretreatment phase (median duration, 3.6 days), 6.3% of the patients receiving prolonged antithrombotic pretreatment experienced an event. Reflecting the high-risk characteristics of our study population, this rate was higher than the daily rate of 1.3% in the Chimeric 7E3 Anti-Platelet Therapy in Refractory Unstable Angina Treatment (CAPTURE) trial26 or the approximate daily rate of 1% found in other studies during conservative treatment.27-29 Compared with other trials,26-29 our patient population was the oldest, comprised the highest proportion of patients with ST-segment abnormalities, and had the highest prevalence of diabetes mellitus. Our study demonstrates that despite recent advances in antithrombotic therapy the risk of large MI or death from any cause is still substantial during conservative treatment of unstable coronary syndromes in unselected high-risk patient settings.
When we designed our study, we chose the duration of the pretreatment phase based on FRISC II.1 Shorter pretreatment phases lasting a median of 1 or 2 days have been instituted in more recent trials.3-4 Nevertheless, the principle message of our study would not have been altered had we chosen a shorter duration of pretreatment. In our study, there was no trade-off between a reduction in postcatheterization events and the incidence of precatheterization events that could be optimized by choosing another duration of pretreatment. On the contrary, our study suggests that the shorter the pretreatment phase the lower the incidence of adverse events.
As in other contemporary studies, 30-day mortality in the entire population was below 1%.1-4,27 Thus, our primary end point and the benefit from early intervention were driven largely by the incidence of MI; one-third of patients with MI will develop new Q waves and two-thirds will not. Consistent with the outcome for nonfatal MI, the observed mortality rates also favored early intervention. These analyses need to be interpreted cautiously, because our study was not powered to analyze each component of our primary end point. In our admittedly underpowered subgroup analyses we did not find any indication that the benefit from early intervention was linked to patients with elevated levels of cardiac troponin T or to those with ST-segment depression, or to a specific modality of definite treatment, such as catheter revascularization or CABG surgery.
In patients with unstable coronary syndromes, intense antithrombotic pretreatment with triple antiplatelet therapy reduces the risk of adverse cardiac events during an unavoidable conservative treatment phase,29 but does not appear to have any further benefit. Conservative pretreatment consumes considerable resources, including an increase in length of hospital stay (median [interquartile range] for prolonged vs early intervention, 7 [6-11] days vs 5 [3-7] days; P<.001) is associated with a substantial risk of cardiac complications, and does not reduce the risk of subsequent revascularization procedures. In patients with unstable coronary syndromes, antithrombotic pretreatment should therefore be kept to the minimum duration required to organize early cardiac catheterization and revascularization.
AUTHOR INFORMATION
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Corresponding Author and Reprints: Franz-Josef Neumann, MD, Herz-Zentrum Bad Krozingen, Südring 15, 79189 Bad Krozingen, Germany (e-mail: Franz-Josef.Neumann{at}herzzentrum.de).
Author Contributions: Dr Neumann, as principal investigator of this study, had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analyses.
Study concept and design: Neumann, Kastrati, Schömig.
Acquisition of data: Neumann, Pogatsa-Murray, Mehilli, Bollwein, Schmitt, Seyfarth, Dirschinger.
Analysis and interpretation of data: Neumann, Kastrati, Bestehorn.
Drafting of the manuscript: Neumann, Kastrati.
Critical revision of the manuscript for important intellectual content: Neumann, Pogatsa-Murray, Mehilli, Bollwein, Bestehorn, Schmitt, Seyfarth, Dirschinger, Schömig.
Statistical expertise: Neumann, Kastrati, Mehilli.
Obtained funding: Neumann.
Administrative, technical, or material support: Neumann, Pogatsa-Murray, Bollwein, Bestehorn, Schmitt, Dirschinger, Schömig.
Study supervision: Neumann, Schmitt, Seyfarth, Dirschinger, Schömig.
Funding/Support: The study was largely funded through institutional funds of the participating centers. There was complementary funding from MSD Sharp&Dohme, GmbH.
Role of the Sponsors: Funding sources had no role in the study design, data collection, data analysis, data interpretation, or writing of the report.
Financial Disclosure: Dr Neumann has received research grants from Merck and speaker fees from Merck and Centocor.
Author Affiliations: Medizinische Klinik (Drs Neumann, Seyfarth, and Schömig) and Deutsches Herzzentrum (Drs Kastrati, Pogatsa-Murray, Mehilli, Bollwein, Schmitt, Dirschinger, and Schömig), Technische Universität München, Munich, Germany; and Herz-Zentrum Bad Krozingen (Drs Neumann and Bestehorn), Bad Krozingen, Germany.
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2009 Focused Updates: ACC/AHA Guidelines for the Management of Patients With ST-Elevation Myocardial Infarction (Updating the 2004 Guideline and 2007 Focused Update) and ACC/AHA/SCAI Guidelines on Percutaneous Coronary Intervention (Updating the 2005 Guideline and 2007 Focused Update): A Report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines
Kushner et al.
J Am Coll Cardiol 2009;54:2205-2241.
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Delays in angiography may cost lives
Rothman and De Palma
Heart 2009;95:1815-1817.
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Potential survival gains in the treatment of myocardial infarction
Chew et al.
Heart 2009;95:1844-1850.
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Antiplatelet agents used for early intervention in acute coronary syndrome: Myocardial salvage versus bleeding complications.
Aranki and Body
J. Thorac. Cardiovasc. Surg. 2009;138:807-810.e7.
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Immediate vs Delayed Intervention for Acute Coronary Syndromes: A Randomized Clinical Trial
Montalescot et al.
JAMA 2009;302:947-954.
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Lipid-rich plaque and myocardial perfusion after successful stenting in patients with non-ST-segment elevation acute coronary syndrome: an optical coherence tomography study
Tanaka et al.
Eur Heart J 2009;30:1348-1355.
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Early versus Delayed Invasive Intervention in Acute Coronary Syndromes
Mehta et al.
NEJM 2009;360:2165-2175.
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Immediate versus deferred coronary angioplasty in non-ST-segment elevation acute coronary syndromes
Riezebos et al.
Heart 2009;95:807-812.
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Delay to angiography and outcomes following presentation with high-risk, non-ST-elevation acute coronary syndromes: results from the Global Registry of Acute Coronary Events
Swanson et al.
Heart 2009;95:211-215.
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Optimizing Clopidogrel Therapy Before Stent Implantation: Should Clinical Setting Be Taken Into Account?
Aradi et al.
J Am Coll Cardiol 2008;52:1349-1349.
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Early Invasive vs Conservative Treatment Strategies in Women and Men With Unstable Angina and Non-ST-Segment Elevation Myocardial Infarction: A Meta-analysis
O'Donoghue et al.
JAMA 2008;300:71-80.
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Possible Benefit to Survival from Early Invasive Strategies in Patients with Acute Coronary Syndromes
Qayyum et al.
ANN INTERN MED 2008;148:884-884.
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2007 Focused Update of the ACC/AHA/SCAI 2005 Guideline Update for Percutaneous Coronary Intervention
American College of Cardiology/American Heart Asso et al.
J Am Coll Cardiol 2008;51:172-209.
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2007 Focused Update of the ACC/AHA/SCAI 2005 Guideline Update for Percutaneous Coronary Intervention: A Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines: 2007 Writing Group to Review New Evidence and Update the ACC/AHA/SCAI 2005 Guideline Update for Percutaneous Coronary Intervention, Writing on Behalf of the 2005 Writing Committee
King et al.
Circulation 2008;117:261-295.
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Time to Coronary Angiography and Outcomes Among Patients With High-Risk Non ST-Segment Elevation Acute Coronary Syndromes: Results From the SYNERGY Trial
Tricoci et al.
Circulation 2007;116:2669-2677.
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ACC/AHA 2007 Guidelines for the Management of Patients With Unstable Angina/Non-ST-Elevation Myocardial Infarction: A Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Writing Committee to Revise the 2002 Guidelines for the Management of Patients With Unstable Angina/Non-ST-Elevation Myocardial Infarction) Developed in Collaboration with the American College of Emergency Physicians, the Society for Cardiovascular Angiography and Interventions, and the Society of Thoracic Surgeons Endorsed by the American Association of Cardiovascular and Pulmonary Rehabilitation and the Society for Academic Emergency Medicine
Anderson et al.
J Am Coll Cardiol 2007;50:e1-e157.
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ACC/AHA 2007 Guidelines for the Management of Patients With Unstable Angina/Non ST-Elevation Myocardial Infarction Executive Summary: A Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Writing Committee to Revise the 2002 Guidelines for the Management of Patients With Unstable Angina/Non ST-Elevation Myocardial Infarction) Developed in Collaboration with the American College of Emergency Physicians, the Society for Cardiovascular Angiography and Interventions, and the Society of Thoracic Surgeons Endorsed by the American Association of Cardiovascular and Pulmonary Rehabilitation and the Society for Academic Emergency Medicine
Anderson et al.
J Am Coll Cardiol 2007;50:652-726.
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The impact of obesity on mortality in UA/non-ST-segment elevation myocardial infarction
Buettner et al.
Eur Heart J 2007;28:1694-1701.
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Guidelines for the diagnosis and treatment of non-ST-segment elevation acute coronary syndromes: The Task Force for the Diagnosis and Treatment of Non-ST-Segment Elevation Acute Coronary Syndromes of the European Society of Cardiology
Authors/Task Force Members et al.
Eur Heart J 2007;28:1598-1660.
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STEMI and NSTEMI: the dangerous brothers
Bode and Zirlik
Eur Heart J 2007;28:1403-1404.
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Acute Coronary Care in the Elderly, Part I: Non-ST-Segment-Elevation Acute Coronary Syndromes: A Scientific Statement for Healthcare Professionals From the American Heart Association Council on Clinical Cardiology: In Collaboration With the Society of Geriatric Cardiology
Alexander et al.
Circulation 2007;115:2549-2569.
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Routine Upstream Initiation vs Deferred Selective Use of Glycoprotein IIb/IIIa Inhibitors in Acute Coronary Syndromes: The ACUITY Timing Trial
Stone et al.
JAMA 2007;297:591-602.
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Effects of revascularization within 14 days of hospital admission due to acute coronary syndrome on 1-year mortality in patients with previous coronary artery bypass graft surgery
Held et al.
Eur Heart J 2007;28:316-325.
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Underuse of revascularisation in acute coronary syndromes
Neumann and Buttner
Heart 2007;93:147-148.
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New aspects in the treatment of acute coronary syndromes without ST-elevation: ICTUS and ISAR-COOL in perspective
Neumann et al.
Eur Heart J Suppl 2007;9:A4-A10.
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Antiplatelet treatment in non-ST-segment elevation acute coronary syndrome patients undergoing percutaneous coronary intervention (ISAR-REACT 2 insight)
Dudek et al.
Eur Heart J Suppl 2007;9:A25-A31.
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The Cardiovascular Disease Continuum Validated: Clinical Evidence of Improved Patient Outcomes: Part II: Clinical Trial Evidence (Acute Coronary Syndromes Through Renal Disease) and Future Directions
Dzau et al.
Circulation 2006;114:2871-2891.
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Bivalirudin for Patients with Acute Coronary Syndromes.
Stone et al.
NEJM 2006;355:2203-2216.
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Benefit of Early Invasive Therapy in Acute Coronary Syndromes: A Meta-Analysis of Contemporary Randomized Clinical Trials
Bavry et al.
J Am Coll Cardiol 2006;48:1319-1325.
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Interventional versus conservative treatment in acute non-ST elevation coronary syndrome: time course of patient management and disease events over one year in the RITA 3 trial
Poole-Wilson et al.
Heart 2006;92:1473-1479.
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Coronary artery disease and outcome in acute congestive heart failure
Purek et al.
Heart 2006;92:598-602.
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Abciximab in Patients With Acute Coronary Syndromes Undergoing Percutaneous Coronary Intervention After Clopidogrel Pretreatment: The ISAR-REACT 2 Randomized Trial
Kastrati et al.
JAMA 2006;295:1531-1538.
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The Role of Risk Stratification in the Decision to Provide Upstream Versus Selective Glycoprotein IIb/IIIa Inhibitors for Acute Coronary Syndromes: A Cost-Effectiveness Analysis
Glaser et al.
J Am Coll Cardiol 2006;47:529-537.
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Optimal Timing of Intervention in Non-ST-Segment Elevation Acute Coronary Syndromes: Insights From the CRUSADE (Can Rapid risk stratification of Unstable angina patients Suppress ADverse outcomes with Early implementation of the ACC/AHA guidelines) Registry
Ryan et al.
Circulation 2005;112:3049-3057.
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Percutaneous coronary intervention guidelines: new aspects for the interventional treatment of acute coronary syndromes
Elsasser and Hamm
Eur Heart J Suppl 2005;7:K5-K9.
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The Year in Non--ST-Segment Elevation Acute Coronary Syndromes
Giugliano and Braunwald
J Am Coll Cardiol 2005;46:906-919.
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Complete myocardial revascularization: between myth and reality
Zimarino et al.
Eur Heart J 2005;26:1824-1830.
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Complete myocardial revascularization: between myth and reality: reply
Zimarino and De Caterina
Eur Heart J 2005;26:1810-1811.
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The declining prevalence of ST elevation myocardial infarction in patients presenting with acute coronary syndromes
Kleiman and White
Heart 2005;91:1121-1123.
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Clopidogrel in non-ST segment elevation acute coronary syndromes: an overview of the submission by the British Cardiac Society and the Royal College of Physicians of London to the National Institute for Clinical Excellence, and beyond
Walsh et al.
Heart 2005;91:1135-1140.
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Routine vs Selective Invasive Strategies in Patients With Acute Coronary Syndromes: A Collaborative Meta-analysis of Randomized Trials
Mehta et al.
JAMA 2005;293:2908-2917.
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To Cath or Not to Cath: That Is No Longer the Question
Bhatt
JAMA 2005;293:2935-2937.
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High-Dose Clopidogrel Loading in Percutaneous Coronary Intervention
Longstreth and Wertz
The Annals of Pharmacotherapy 2005;39:918-922.
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The year in interventional cardiology
O'Neill et al.
J Am Coll Cardiol 2005;45:1117-1134.
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Guidelines for Percutaneous Coronary Interventions: The Task Force for Percutaneous Coronary Interventions of the European Society of Cardiology
Authors/Task Force Members et al.
Eur Heart J 2005;26:804-847.
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A Simplified Approach to the Management of Non-ST-Segment Elevation Acute Coronary Syndromes
Gluckman et al.
JAMA 2005;293:349-357.
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Troponin in patients with chest pain
Curzen
BMJ 2004;329:1357-1358.
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The comprehensive approach to ischemic heart disease by cardiovascular magnetic resonance imaging: Are we there yet?
Kramer
J Am Coll Cardiol 2004;44:2182-2184.
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High clopidogrel loading dose during coronary stenting: effects on drug response and interindividual variability
Angiolillo et al.
Eur Heart J 2004;25:1903-1910.
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Is there a gender paradox in the early invasive strategy for non ST-segment elevation acute coronary syndromes?
Elkoustaf and Boden
Eur Heart J 2004;25:1559-1561.
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Association of revascularisation with low mortality in non-ST elevation acute coronary syndrome, a report from GUSTO IV-ACS
Ottervanger et al.
Eur Heart J 2004;25:1494-1501.
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Antithrombotic Therapy During Percutaneous Coronary Intervention: The Seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy
Popma et al.
Chest 2004;126:576S-599S.
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Renal function and long term mortality after unstable angina/non-ST segment elevation myocardial infarction treated very early and predominantly with percutaneous coronary intervention
Mueller et al.
Heart 2004;90:902-907.
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Fractionating Heparins and Their Clinical Trial Data--Something for Everyone
Das and Moliterno
JAMA 2004;292:101-103.
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The year in interventional cardiology
O'Neill and Dixon
J Am Coll Cardiol 2004;43:875-890.
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Additional articles abstracted in ACP Journal Club
Evid. Based Med. 2004;9:35-35.
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Implications of Upstream Glycoprotein IIb/IIIa Inhibition and Coronary Artery Stenting in the Invasive Management of Unstable Angina/Non-ST-Elevation Myocardial Infarction: A Comparison of the Thrombolysis In Myocardial Infarction (TIMI) IIIB Trial and the Treat angina with Aggrastat and determine Cost of Therapy with Invasive or Conservative Strategy (TACTICS)-TIMI 18 Trial
Sabatine et al.
Circulation 2004;109:874-880.
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"Cooling-Off" vs Immediate Revascularization for Patients With Acute Coronary Syndromes
Goodman
JAMA 2004;291:691-691.
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Prolonged antithrombotics do not improve unstable coronary syndrome
BMJ 2004;328:0-0.
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Percutaneous coronary intervention in diabetic patients with non-ST-segment elevation acute coronary syndromes
Roffi and Topol
Eur Heart J 2004;25:190-198.
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JournalScan
Malik
Heart 2003;89:1467-1468.
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Should We Prolong Pre-Cath Antithrombotic Treatment in High-Risk ACS Patients?
Journal Watch Cardiology 2003;2003:2-2.
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