Acute Catheterization And Urgent Intervention Triage Strategy Research Articles

Intra-Procedural Stent Thrombosis: A New Risk Factor for Adverse Outcomes in Patients Undergoing Percutaneous Coronary Intervention for Acute Coronary Syndromes

The aim of this study was to examine the incidence, correlates, and consequences of intra-procedural stent thrombosis (IPST) in patients with acute coronary syndromes (ACS). Stent thrombosis (ST) is a rare but serious complication of percutaneous coronary intervention (PCI). The Academic Research Consortium definition of ST excludes events occurring during PCI. Angiograms from the ACUITY (Acute Catheterization and Urgent Intervention Triage StrategY) and HORIZONS-AMI (Harmonizing Outcomes with RevascularIZatiON and Stents in Acute Myocardial Infarction) trials were reviewed frame-by-frame at an independent core laboratory for the occurrence of IPST. Patients with versus without IPST were compared to identify baseline characteristics associated with IPST and demonstrate the independent association between IPST and adjudicated events at 30 days and 1 year. Intra-procedural ST occurred in 47 (0.7%) of 6,591 patients. The occurrence of IPST was associated with ST-segment elevation myocardial infarction presentation, high white blood cell count, treatment of thrombotic and bifurcation lesions, bivalirudin monotherapy, bail-out IIb/IIIa inhibitor use, and implantation of bare-metal (rather than drug-eluting) stents. Major adverse ischemic events were markedly higher in patients with versus without IPST, including mortality at 30 days (12.9% vs. 1.4%, p < 0.0001) and 1 year (12.9% vs. 3.1%, p < 0.0001). Out-of-lab Academic Research Consortium definite or probable ST also occurred significantly more often among IPST patients at 30 days (17.4% vs. 1.8%, p < 0.0001) and 1 year (19.9% vs. 2.7%, p < 0.0001). Intra-procedural ST was a significant independent predictor of 1-year mortality (hazard ratio: 3.86, 95% confidence interval: 1.66 to 9.00, p = 0.002). Intra-procedural ST is a relatively rare complication of PCI in ACS but is strongly associated with subsequent out-of-lab ST and mortality. Intra-procedural ST should be considered as a distinct category of ST and routinely reported, particularly for ACS patients.

Development and Validation of a Stent Thrombosis Risk Score in Patients With Acute Coronary Syndromes

This study sought to develop a practical risk score to predict the risk of stent thrombosis (ST) after percutaneous coronary intervention (PCI) for acute coronary syndromes (ACS). ST is a rare, yet feared complication after PCI with stent implantation. A risk score for ST after PCI in ACS can be a helpful tool to personalize risk assessment. This study represents a patient-level pooled analysis of 6,139 patients undergoing PCI with stent implantation for ACS in the HORIZONS-AMI (Harmonizing Outcomes With Revascularization and Stents in Acute Myocardial Infarction) and ACUITY (Acute Catheterization and Urgent Intervention Triage Strategy) trials who were randomized to treatment with bivalirudin versus heparin plus a glycoprotein IIb/IIIa inhibitor. The cohort was randomly divided into a risk score development cohort (n = 4,093) and a validation cohort (n = 2,046). Cox regression methods were used to identify clinical, angiographic, and procedural characteristics associated with Academic Research Consortium-defined definite/probable ST at 1 year. Each covariate in this model was assigned an integer score based on the regression coefficients. Variables included in the risk score were type of ACS (ST-segment elevation myocardial infarction, non-ST-segment elevation ACS with ST deviation, or non-ST-segment elevation ACS without ST changes), current smoking, insulin-dependent diabetes mellitus, prior PCI, baseline platelet count, absence of early (pre-PCI) anticoagulant therapy, aneurysmal/ulcerated lesion, baseline TIMI (Thrombolysis In Myocardial Infarction) flow grade 0/1, final TIMI flow grade <3, and number of treated vessels. Risk scores 1 to 6 were considered low risk, 7 to 9 intermediate risk, and 10 or greater high risk for ST. Rates of ST at 1 year in low-, intermediate-, and high-risk categories were 1.36%, 3.06%, and 9.18%, respectively, in the development cohort (p for trend <0.001), and 1.65%, 2.77%, and 6.45% in the validation cohort (p for trend = 0.006). The C-statistic for this risk score was over 0.65 in both cohorts. The individual risk of ST can be predicted using a simple risk score based on clinical, angiographic, and procedural variables. (Harmonizing Outcomes With Revascularization and Stents in Acute Myocardial Infarction [HORIZONS-AMI]; NCT00433966) (Comparison of Angiomax Versus Heparin in Acute Coronary Syndromes [ACUITY]; NCT00093158).

A New Score for Risk Stratification of Patients With Acute Coronary Syndromes Undergoing Percutaneous Coronary Intervention: The ACUITY-PCI (Acute Catheterization and Urgent Intervention Triage Strategy–Percutaneous Coronary Intervention) Risk Score

This study sought to develop a new score specific for patients with non-ST-segment elevation acute coronary syndromes (NSTEACS) undergoing percutaneous coronary intervention (PCI) (the ACUITY-PCI [Acute Catheterization and Urgent Intervention Triage Strategy-Percutaneous Coronary Intervention] risk score). The TIMI (Thrombolysis In Myocardial Infarction) and GRACE (Global Registry for Acute Coronary Events) risk scores are recommended for risk stratification of patients with NSTEACS. However, these scores were not optimized for patients undergoing an early invasive strategy with PCI. The ACUITY-PCI risk score was created from data for 1,692 patients enrolled in the formal angiographic substudy of the ACUITY (Acute Catheterization and Urgent Intervention Triage Strategy) trial by integrating clinical, angiographic, laboratory, and electrocardiographic variables selected by multivariable analysis. The score was subsequently validated in a different population of 846 patients and compared with the GRACE and TIMI risk scores, and the SYNTAX (Synergy Between PCI with Taxus and Cardiac Surgery) and Clinical SYNTAX scores. Six variables (2 clinical, 1 laboratory/electrocardiographic, and 3 angiographic) were included in the ACUITY-PCI score: insulin-treated diabetes; renal insufficiency; baseline cardiac biomarker elevation or ST-segment deviation; bifurcation lesion; small vessel/diffuse coronary artery disease; and the extent of coronary artery disease. Event rates increased significantly across tertiles of ACUITY-PCI score. Compared with the other scores, the ACUITY-PCI score had the best discrimination (C-statistic), calibration (Hosmer-Lemeshow statistic), and index of separation. Moreover, the net reclassification improvement varied from 9% to 38% and the integrated discrimination index from 1.9% to 2.7%. The ACUITY-PCI risk score is a new tool integrating clinical, angiographic, and laboratory/electrocardiographic variables specifically developed for patients with NSTEACS undergoing PCI. This score displayed better prognostic accuracy in terms of discrimination and calibration than other currently available scores for risk stratification of patients with NSTEACS. (Comparison of Angiomax Versus Heparin in Acute Coronary Syndromes [ACS]; NCT00093158).

Letter by Sharma et al Regarding Article, “Impact of the Presence and Extent of Incomplete Angiographic Revascularization After Percutaneous Coronary Intervention in Acute Coronary Syndromes: The Acute Catheterization and Urgent Intervention Triage Strategy (ACUITY) Trial”

To the Editor: In the Acute Catheterization and Urgent Intervention Triage Strategy (ACUITY) trial, Rosner and colleagues1 evaluate the impact of the presence and extent of incomplete angiographic revascularization after percutaneous coronary intervention in acute coronary syndromes. They should be commended for their attempts to answer a pertinent debate on the clinical importance of incomplete coronary revascularization (ICR) after percutaneous coronary intervention. However, a few interesting points …

Response to Letter Regarding Article, “Impact of the Presence and Extent of Incomplete Angiographic Revascularization After Percutaneous Coronary Intervention in Acute Coronary Syndromes: The Acute Catheterization and Urgent Intervention Triage Strategy (ACUITY) Trial”

Sharma et al question whether incomplete revascularization (ICR) after percutaneous coronary intervention is a bystander reflecting greater comorbidities and more diffuse atherosclerosis or results in increased major adverse cardiovascular events (MACE). With ICR defined using a threshold diameter stenosis ≥50% on quantitative coronary angiography in our original multivariable model, ICR was an independent predictor of 1-year MACE (hazard ratio, 1.36; 95% confidence interval, 1.12–1.64; P =0.002).1 Although we attempted to adjust for other covariates (including some of those suggested by Sharma et al), not all of these were available or fully represented in this database. For example, baseline left ventricular ejection fraction was present in only 62.8% of patients and was …

Bivalirudin Versus Heparin Plus a Glycoprotein IIb/IIIa Inhibitor in Patients With Non–ST-Segment Elevation Myocardial Infarction Undergoing Percutaneous Coronary Intervention After Clopidogrel Pretreatment

The optimal antithrombotic therapy for patients with non-ST-segment elevation myocardial infarction undergoing percutaneous coronary intervention is not well defined. We investigated the efficacy and safety of bivalirudin versus heparin plus a glycoprotein IIb/IIIa inhibitor (GPI) in patients with non-ST-segment elevation myocardial infarction undergoing percutaneous coronary intervention after clopidogrel pretreatment. This study included 3798 clopidogrel-pretreated patients with non-ST-segment elevation myocardial infarction undergoing percutaneous coronary intervention, who were randomly assigned to receive bivalirudin (n=1928) or heparin (unfractionated heparin or enoxaparin; n=1870) plus a GPI in the setting of the Acute Catheterization and Urgent Intervention Triage Strategy (ACUITY) and Intracoronary Stenting and Antithrombotic Regimen: Rapid Early Action for Coronary Treatment (ISAR-REACT) 4 trials. Major end points were a composite of death, recurrent myocardial infarction or urgent target vessel revascularization (efficacy end point), major bleeding (safety end point), and the composite of death, recurrent myocardial infarction, urgent target vessel revascularization, or major bleeding (net adverse clinical events [NACE]) at 30 days. The incidence of the efficacy end point was 10.6% (n=205) in the bivalirudin group versus 10.2% (n=191) in the heparin plus a GPI group (OR, 1.04; 95% CI, 0.85-1.27; P=0.69). The incidence of safety end point was 3.4% (n=66) in the bivalirudin group versus 6.3% (n=117) in the heparin plus a GPI group (OR, 0.54 [0.40-0.72]; P<0.001). NACE occurred in 258 patients (13.4%) in the bivalirudin group versus 275 patients (14.7%) in the heparin plus a GPI group (OR, 0.90 [0.76-1.06]; P=0.21). NACE rates were not significantly different between bivalirudin and heparin plus a GPI in patients with non-ST-segment elevation myocardial infarction undergoing percutaneous coronary intervention after clopidogrel pretreatment. Although no significant difference in efficacy was seen in terms of suppression of adverse ischemic events, bivalirudin was superior to heparin plus a GPI in terms of reducing bleeding events. URL: http://www.clinicaltrials.gov. Unique Identifier: NCT00093158 and NCT00373451.

Outcomes of Patients With Prior Coronary Artery Bypass Grafting and Acute Coronary Syndromes: Analysis From the ACUITY (Acute Catheterization and Urgent Intervention Triage Strategy) Trial

This study sought to assess the contemporary outcomes of patients with prior coronary artery bypass graft (CABG) who present with moderate and high-risk acute coronary syndromes (ACS) and are treated with an early invasive strategy and contemporary antithrombin regimens. The prognosis of patients with ACS and prior CABG in relation to triage strategy and contemporary antithrombotic regimens is unknown. In the ACUITY (Acute Catheterization and Urgent Intervention Triage Strategy) trial, 2,475 of 13,764 patients (18.0%) with ACS managed with an early invasive strategy had previously undergone CABG. Their outcomes were examined according to treatment and randomized antithrombin regimen. Prior CABG was associated with older age, more frequent comorbidities, higher Thrombolysis In Myocardial Infarction risk score, and lower left ventricular ejection fraction. Patients with versus without prior CABG were less likely to undergo (repeat) CABG and were more likely to be managed medically. At 1 year, patients with versus without prior CABG had higher rates of major adverse cardiac events (MACE) (22.5% vs. 15.2%, p < 0.0001) due to greater mortality (5.4% vs. 3.9%, p < 0.0001), myocardial infarction (10.0% vs. 6.8%, p < 0.0001), and unplanned revascularization (13.1% vs. 8.2%, p < 0.0001). History of CABG was an independent predictor of MACE. The 1-year MACE rates were not significantly different after randomization to bivalirudin versus heparin plus a glycoprotein IIb/IIIa inhibitor (odds ratio: 1.24, 95% confidence interval: 0.90 to 1.70). Despite the progress in the treatment of coronary artery disease, patients with prior CABG and ACS have a poor prognosis, substantially worse than for those without prior CABG. Whereas bivalirudin monotherapy was an acceptable treatment for these patients, it did not improve their prognoses.

Circulation: Clinical Summaries

<i>Circulation:</i> Clinical Summaries

Impact of the Presence and Extent of Incomplete Angiographic Revascularization After Percutaneous Coronary Intervention in Acute Coronary Syndromes

Background— The clinical significance of incomplete coronary revascularization (ICR) after percutaneous coronary intervention in patients with acute coronary syndromes is unknown. Methods and Results— We performed quantitative angiography of the entire coronary tree in 2954 patients with acute coronary syndromes in the Acute Catheterization and Urgent Intervention Triage Strategy (ACUITY) trial. ICR was variably defined if any lesion with diameter stenosis (DS) cutoffs ranging from ≥30% to ≥70% with reference vessel diameter ≥2.0 mm remained after percutaneous coronary intervention. The primary outcome was 1-year composite rate of major adverse cardiac events (death, myocardial infarction, or ischemia-driven unplanned revascularization). With the use of DS cutoffs ≥30%, ≥40%, ≥50%, ≥60%, and ≥70%, the prevalence of ICR after percutaneous coronary intervention was 75%, 55%, 37%, 25%, and 17%, respectively. The 1-year major adverse cardiac event rate was increased among patients with ICR using all of the DS cutoffs. ICR (≥50% DS) was associated with higher 1-year rates of myocardial infarction (12.0% versus 8.2%; hazard ratio, 1.50; 95% confidence interval, 1.18–1.89; P =0.0007) and ischemia-driven unplanned revascularization (15.7% versus 10.2%; hazard ratio, 1.58; 95% confidence interval, 1.28–1.96; P &lt;0.0001), with a trend toward increased mortality (3.1% versus 2.2%; hazard ratio, 1.43; 95% confidence interval, 0.90–2.27; P =0.13). By multivariable analysis, ICR (≥50% DS) was an independent predictor of 1-year major adverse cardiac events (hazard ratio, 1.36; 95% confidence interval, 1.12–1.64; P =0.002). The impact of ICR on major adverse cardiac events was similar regardless of chronic total occlusion presence, but it was more pronounced with a greater number of nonrevascularized lesions. Conclusions— Depending on the threshold of percent DS, ICR was present in 17% to 75% of patients with acute coronary syndromes after percutaneous coronary intervention. Regardless of the threshold, ICR was strongly associated with 1-year myocardial infarction, ischemia-driven unplanned revascularization, and major adverse cardiac events. Clinical Trial Registration— URL: http://www.clinicaltrials.gov . Unique identifier: NCT00093158.

Intraprocedural Thrombotic Events During Percutaneous Coronary Intervention in Patients With Non–ST-Segment Elevation Acute Coronary Syndromes Are Associated With Adverse Outcomes: Analysis From the ACUITY (Acute Catheterization and Urgent Intervention Triage Strategy) Trial

The purpose of this study was to assess the prognostic impact of intraprocedural thrombotic events (IPTE) during percutaneous coronary intervention (PCI). Ischemic complications of PCI are infrequent but prognostically important. How often these events are a consequence of intraprocedural complications is unknown, with only limited data assessing the occurrence and importance of IPTE. A total of 3,428 patients who underwent PCI for non-ST-segment elevation acute coronary syndrome in the ACUITY (Acute Catheterization and Urgent Intervention Triage Strategy) trial underwent detailed frame-by-frame core laboratory angiographic analysis. An IPTE, defined as the development of new or increasing thrombus, abrupt vessel closure, no reflow, slow reflow, or distal embolization at any time during the procedure, occurred in 121 patients (3.5%). Patients with IPTE had higher in-hospital, 30-day, and 1-year major adverse cardiac event rates than patients without IPTE (25.6% vs. 6.3% in-hospital, 30.6% vs. 9.3% at 30 days, and 37.0% vs. 20.5% at 1 year; p < 0.0001 for each). An IPTE was strongly associated with Q-wave myocardial infarction and out-of-laboratory definite/probable stent thrombosis (in-hospital 3.3% vs. 0.5%, p = 0.006; 30 days 5.8% vs. 1.3%, p < 0.0001; and 1 year 6.7% vs. 2.0%, p = 0.0002). Unplanned revascularization, target vessel revascularization, and major bleeding not associated with coronary artery bypass graft surgery were also increased among patients with IPTE, as was overall 30-day mortality (3.3% vs. 0.7%, p = 0.002). Moreover, IPTE was an independent predictor of 30-day and 1-year composite death/myocardial infarction, stent thrombosis, and major adverse cardiac events. Although infrequent among patients undergoing early PCI for moderate and high-risk non-ST-segment elevation acute coronary syndrome, IPTE was strongly associated with subsequent adverse outcomes including death, myocardial infarction, and stent thrombosis.

Quantification and Impact of Untreated Coronary Artery Disease After Percutaneous Coronary Intervention: The Residual SYNTAX (Synergy Between PCI With Taxus and Cardiac Surgery) Score

The purpose of this study was to quantify the extent and complexity of residual coronary stenoses following percutaneous coronary intervention (PCI) and to evaluate its impact on adverse ischemic outcomes. Incomplete revascularization (IR) after PCI is common, and most studies have suggested that IR is associated with a worse prognosis compared with complete revascularization (CR). However, formal quantification of the extent and complexity of residual atherosclerosis after PCI has not been performed. The baseline Synergy Between PCI With Taxus and Cardiac Surgery (SYNTAX) score (bSS) from 2,686 angiograms from patients with moderate- and high-risk acute coronary syndrome (ACS) undergoing PCI enrolled in the prospective ACUITY (Acute Catheterization and Urgent Intervention Triage Strategy) trial was determined. The SS after PCI was also assessed, generating the “residual” SS (rSS). Patients with rSS >0 were defined as having IR and were stratified by rSS tertiles, and their outcomes were compared to the CR group. The bSS was 12.8 ± 6.7, and after PCI the rSS was 5.6 ± 2.2. Following PCI, 1,084 patients (40.4%) had rSS = 0 (CR), 523 (19.5%) had rSS >0 but ≤2, 578 (21.5%) had rSS >2 but ≤8, and 501 patients (18.7%) had rSS >8. Age, insulin-treated diabetes, hypertension, smoking, elevated biomarkers or ST-segment deviation, and lower ejection fraction were more frequent in patients with IR compared with CR. The 30-day and 1-year rates of ischemic events were significantly higher in the IR group compared with the CR group, especially those with high rSS. By multivariable analysis, rSS was a strong independent predictor of all ischemic outcomes at 1 year, including all-cause mortality (hazard ratio: 1.05, 95% confidence interval: 1.02 to 1.09, p = 0.006). The rSS is useful to quantify and risk-stratify the degree and complexity of residual stenosis after PCI. Specifically, rSS >8.0 after PCI in patients with moderate- and high-risk ACS is associated with a poor 30-day and 1-year prognosis. (Comparison of Angiomax Versus Heparin in Acute Coronary Syndromes; NCT00093158)

Impact of major bleeding and blood transfusions after cardiac surgery: Analysis from the Acute Catheterization and Urgent Intervention Triage strategY (ACUITY) trial

Prior retrospective studies have identified a relationship between bleeding after cardiac surgery and subsequent mortality. Whether this is attributable to bleeding, anemia, or transfusions is undetermined. ACUITY was an international prospective trial of patients with acute coronary syndromes. Coronary artery bypass grafting (CABG) before hospital discharge was performed in 1,491 patients. Major bleeding was adjudicated as CABG- or non-CABG related. The relationship between CABG-related bleeding and 1-year mortality was determined using a time-updated covariate-adjusted Cox model. Coronary artery bypass grafting-related major bleeding after surgery occurred in 789 patients (52.9%); allogeneic blood product transfusions were administered in 612 patients (41.0%), including red blood cell (RBC) transfusions in 570 (38.2%, range 1-53 U), platelet transfusions in 180 (12.1%), and fresh-frozen plasma in 195 (13.1%). One-year mortality occurred in 95 patients (6.4%). Red blood cell transfusion (but not transfusion of platelets or fresh-frozen plasma, CABG-related major bleeding per se, or nadir hemoglobin) was an independent predictor of 1-year mortality, but only after transfusion of ≥4 U (adjusted hazard ratio for death after transfusion of 1-3, 4-6, and ≥7 RBC units = 0.74, 2.01, and 5.22, respectively). Of the 95 deaths after CABG, 23 (24.2%) were attributable to CABG-related RBC transfusions. In patients with acute coronary syndromes, RBC transfusion of ≥4 U after CABG is strongly associated with subsequent mortality. Future strategies should focus on reducing major hemorrhagic complications and RBC transfusions after CABG.

Comparison of clinical and angiographic prognostic risk scores in patients with acute coronary syndromes: Analysis from the Acute Catheterization and Urgent Intervention Triage StrategY (ACUITY) trial

Several prognostic risk scores have been developed for patients with coronary artery disease, but their comparative use in patients with non-ST-segment elevation acute coronary syndromes (NSTEACS) undergoing percutaneous coronary intervention (PCI) has not been examined. We therefore investigated the accuracy of the Synergy Between PCI With Taxus and Cardiac Surgery (SYNTAX) score, Clinical Synergy Between PCI With Taxus and Cardiac Surgery score (CSS), New Risk Stratification (NERS) score (NERS), Age, Creatinine, Ejection Fraction (ACEF) score, Global Registry for Acute Coronary Events (GRACE) score, and Thrombolysis in Myocardial Infarction (TIMI) score for risk assessment of 1-year mortality, cardiac mortality, myocardial infarction, target vessel revascularization, and stent thrombosis in patients with NSTEACS undergoing PCI. The 6 scores were determined in 2,094 patients with NSTEACS treated with PCI enrolled in the angiographic substudy of the ACUITY trial. The prognostic accuracy of the 6 scores was assessed using the c statistic for discrimination and the Hosmer-Lemeshow test for calibration. The index of separation and net reclassification improvement (NRI) were also determined. Scores incorporating clinical and angiographic variables (CSS and NERS) showed the best tradeoff between discrimination and calibration for most end points, with the best discrimination for all end points and good calibration for most of them. The CSS had the best index of separation for most ischemic endpoints and displayed an NRI for cardiac death and myocardial infarction (MI) compared to the other scores, whereas NERS displayed an NRI for all-cause death and target vessel revascularization. The 3 scores-CSS, NERS, and SYNTAX-were the only scores to have both good discrimination and calibration for cardiac mortality. In patients with NSTEACS undergoing PCI, risk scores incorporating clinical and angiographic variables had the highest predictive accuracy for a broad spectrum of ischemic end points.

Prognostic Significance of Elevated Baseline Troponin in Patients With Acute Coronary Syndromes and Chronic Kidney Disease Treated With Different Antithrombotic Regimens

Elevation of baseline cardiac troponin in patients presenting with acute coronary syndromes (ACS) confers an adverse prognosis. The prognostic value of troponin elevation in patients with chronic kidney disease (CKD) and ACS is less certain. In the ACUITY (Acute Catheterization and Urgent Intervention Triage strategy) trial, 13 819 patients with moderate and high-risk ACS were assigned randomly to receive heparin plus a glycoprotein IIb/IIIa inhibitor (GPI), bivalirudin plus a GPI, or bivalirudin monotherapy. Among 2179 patients with CKD (creatinine clearance <60 mL/min), baseline troponin elevation was present in 1291 patients (59.2%). Major bleeding and major adverse cardiac events (MACE), including death, myocardial infarction (MI), or unplanned revascularization, were examined according to baseline troponin status and randomization arm. Patients with CKD in whom the baseline troponin level was elevated had significantly higher rates of death, MI, and MACE at 30 days and 1 year compared with CKD patients without elevated baseline troponin. By multivariable analysis, baseline troponin elevation in patients with CKD was an independent predictor of composite death or MI at 30 days (hazard ratio [95% CI]=2.05 [1.48, 2.83], P<0.0001) and 1 year (1.72 [1.36, 2.17], P<0.0001). In CKD patients with baseline troponin elevation, bivalirudin monotherapy compared with heparin plus a GPI significantly reduced the 30-day rates of major bleeding with nonsignificantly different rates of MACE at 30 days and 1 year. In patients with ACS and CKD, baseline troponin elevation is associated with significantly worse short- and long-term clinical outcomes. Bivalirudin monotherapy safely reduces major bleeding in ACS patients with CKD and baseline troponin elevation. URL: http://www.clinicaltrials.gov. Unique identifier: NCT00093158.

Predictors and Implications of Stent Thrombosis in Non–ST-Segment Elevation Acute Coronary Syndromes

The frequency, predictors, and consequences of stent thrombosis (ST) in patients with non-ST-segment elevation acute coronary syndromes (NSTE-ACS) have been incompletely studied. We sought to investigate the incidence, predictors, and clinical implications of ST occurring within 1 year after percutaneous coronary intervention in patients with NSTE-ACS. The Acute Catheterization and Urgent Intervention Triage StrategY (ACUITY) trial was a large-scale, prospective, randomized trial of antithrombotic regimens in patients with NSTE-ACS. The present analysis includes 7162 patients in whom stents were implanted. At 1 year, definite/probable ST occurred in 146 patients (2.2%), including 94 definite and 52 probable events. There were 100 episodes (1.4%) of early ST (within the first 30 days) and 46 episodes (0.8%) of late ST (between 30 days and 1 year). The incidence of ST within 1 year was similar in patients treated with drug-eluting stents or bare metal stents (hazard ratio, 0.86; 95% confidence interval, 0.62-1.20; P=0.38) and was independent of procedural antithrombotic treatment. Patients with ST compared with those without ST had strikingly higher 1-year rates of cardiac mortality (32.4% versus 2.9%, P<0.0001), myocardial infarction (82.6% versus 7.6%, P<0.0001), and target vessel revascularization (79.6% versus 7.4%, P<0.0001). Independent predictors of 1-year definite/probable ST were insulin-treated diabetes mellitus, number of diseased vessels, and ST-segment deviation ≥1 mm. Compared with elective stent implantation, ST occurs with increased frequency in the first year after stent implantation in patients with NSTE-ACS, especially within the first 30 days, and is associated with marked increases in cardiac mortality and adverse events. Insulin-treated diabetes, number of diseased vessels, and dynamic ST-segment changes were independent predictors of 1-year ST in NSTE-ACS.

Prognostic Significance of Coronary Thrombus in Patients Undergoing Percutaneous Coronary Intervention for Acute Coronary Syndromes: A Subanalysis of the ACUITY (Acute Catheterization and Urgent Intervention Triage strategY) Trial

The objective of this study is to investigate the incidence and clinical implications of thrombus on baseline angiography among patients presenting with non-ST-segment elevation acute coronary syndromes (ACS) undergoing percutaneous coronary intervention (PCI). Given current advances in the pharmacological and mechanical treatment of ACS patients managed with an early invasive strategy, the incidence and prognostic importance of pre-procedural lesion thrombus is warranted. In the ACUITY (Acute Catheterization and Urgent Intervention Triage strategY) trial, a total of 3,627 patients with moderate- and high-risk ACS undergoing PCI had their baseline and final post-PCI angiograms analyzed by an independent angiographic core laboratory. Patients with thrombus (n = 530 [15%]) compared with those without thrombus had higher rates of impaired final epicardial coronary flow (final Thrombolysis In Myocardial Infarction [TIMI] flow grade 3: 89.6% vs. 97.1%, p < 0.0001). Thrombus was an independent predictor of 30 day death (odds ratio [OR]: 3.16 [95% confidence interval (CI): 1.20 to 8.37], p = 0.02), and myocardial infarction (MI) at 30 days (OR: 1.62 [95% CI: 1.17 to 2.24], p = 0.003) and at 1 year (OR: 1.56 [95% CI: 1.16 to 2.08], p = 0.003). Patients with thrombus had significantly higher rates of stent thrombosis (ST) compared with patients without thrombus at 30 days (2.8% vs. 1.1%, p = 0.002) and at 1 year (3.7% vs. 1.8%, p = 0.003), and thrombus was an independent predictor of ST at both 30 days (OR: 2.61 [95% CI: 1.38 to 4.91]) and 1 year (OR: 2.98 [95% CI: 1.64 to 5.42]). Pre-procedural thrombus was present in 15% of moderate- and high-risk ACS patients undergoing PCI in the ACUITY trial. Baseline thrombus predicts increased ischemic complications at 30 days including a 3-fold increased risk of death as well as MI up to 1 year. Further evaluation of adjunctive pharmacotherapy is needed in this high-risk population.

Impact of Bleeding on Mortality After Percutaneous Coronary Intervention: Results From a Patient-Level Pooled Analysis of the REPLACE-2 (Randomized Evaluation of PCI Linking Angiomax to Reduced Clinical Events), ACUITY (Acute Catheterization and Urgent Intervention Triage Strategy), and HORIZONS-AMI (Harmonizing Outcomes With Revascularization and Stents in Acute Myocardial Infarction) Trials

This study sought to develop a risk score predictive of bleeding in patients undergoing percutaneous coronary intervention (PCI) and to investigate the impact of bleeding on subsequent mortality. Bleeding complications after PCI have been independently associated with early and late mortality. This study represents a patient-level pooled analysis including 17,034 patients undergoing PCI from 3 large, randomized trials of bivalirudin versus heparin plus glycoprotein IIb/IIIa inhibitors, including the REPLACE-2 (Randomized Evaluation of PCI Linking Angiomax to Reduced Clinical Events), ACUITY (Acute Catheterization and Urgent Intervention Triage Strategy), and HORIZONS-AMI (Harmonizing Outcomes With Revascularization and Stents in Acute Myocardial Infarction) trials. We developed a risk score to predict noncoronary artery bypass graft (CABG)-related TIMI (Thrombolysis In Myocardial Infarction) major bleeding and evaluated the impact of various types of bleeding on 1-year mortality. A non-CABG-related TIMI major bleed occurred within 30 days in 267 patients (1.6%), and death occurred in 497 patients (2.9%) within 1 year. A risk score was developed to predict the bleeding risk of patients undergoing PCI, consisting of 7 variables (serum creatinine, age, sex, presentation, white blood cell count, cigarette smoking, and randomized treatment). The TIMI major bleeding rates increased by bleeding risk score groups: from 0.4% for those in the lowest to 5.8% for those in the highest risk group. Non-CABG-related TIMI major bleeding and the occurrence of myocardial infarction within 30 days were independent predictors of subsequent mortality, with respective hazard ratios of 4.2 and 2.9, each p < 0.001. Ranked in order of severity, TIMI major bleeding, blood transfusion without TIMI bleed, TIMI minor bleeding requiring blood transfusion, and TIMI minor bleeding not requiring blood transfusion were independent predictors of subsequent mortality with hazard ratios of 4.89, 2.91, 2.73, and 1.66, respectively. Isolated hematomas were not predictive of subsequent mortality. Non-CABG-related bleeding within 30 days is strongly associated with an increased risk of subsequent mortality at 1 year in patients undergoing PCI for all indications. A risk score was established to calculate the bleeding risk for patients undergoing PCI, allowing therapeutic decision making to minimize the incidence of bleeding.

Prognostic Value of the SYNTAX Score in Patients With Acute Coronary Syndromes Undergoing Percutaneous Coronary Intervention: Analysis From the ACUITY (Acute Catheterization and Urgent Intervention Triage StrategY) Trial

We sought to investigate the predictive value of the SYNTAX (Synergy Between PCI With Taxus and Cardiac Surgery) score (SS) for risk assessment of 1-year clinical outcomes in patients with non-ST-segment elevation acute coronary syndromes undergoing percutaneous coronary intervention (PCI). In the SYNTAX trial, the SS was effective in risk-stratifying patients with left main and triple-vessel coronary disease, the majority of whom had stable ischemic heart disease. The SS was determined in 2,627 patients with non-ST-segment elevation acute coronary syndromes undergoing PCI in the angiographic substudy of the ACUITY (Acute Catheterization and Urgent Intervention Triage StrategY) trial. Patients were stratified according to tertiles of the SS: <7 (n = 854), ≥ 7 and <13 (n = 825), and ≥ 13 (n = 948). Among patients in the first, second, and third SS tertiles, the 1-year rates of mortality were 1.5%, 1.6%, and 4.0%, respectively (p = 0.0005); the cardiac mortality rates were 0.2%, 0.9%, and 2.7%, respectively (p < 0.0001); the myocardial infarction (MI) rates were 6.3%, 8.3%, and 12.9%, respectively (p < 0.0001); and the target vessel revascularization (TVR) rates were 7.4%, 7.0%, and 9.8%, respectively (p = 0.02). By multivariable analysis, the SS was an independent predictor of 1-year death (hazard ratio [HR]: 1.04, 95% confidence interval [CI]: 1.01 to 1.07; p = 0.005), cardiac death (HR: 1.06, 95% CI: 1.03 to 1.09; p = 0.0002), MI (HR: 1.03, 95% CI: 1.02 to 1.05; p < 0.0001), and TVR (HR: 1.03, 95% CI: 1.02 to 1.05; p < 0.0001). The SS affected death, cardiac death, and MI both within the first 30 days after PCI and between 30 days and 1 year, whereas it affected TVR primarily within the first 30 days. The predictive value of an increased SS was consistent among multiple pre-specified subgroups. In patients with non-ST-segment elevation acute coronary syndromes undergoing PCI, the SS is an independent predictor of the 1-year rates of death, cardiac death, MI, and TVR. (Comparison of Angiomax Versus Heparin in Acute Coronary Syndromes [ACS]; NCT00093158).

STEMI Patients—The More You Bleed, the More You Die: A Comparison Between Classifications

In patients with acute coronary syndromes, an increase in hemorrhagic complications has been observed, and bleeding is now the most frequent noncardiac complication in these patients. Clinical trials and registries have used different scales to classify the severity of bleeding; so far, none of them has been developed for ST-segment elevation myocardial infarction (STEMI) patients in the era of primary percutaneous coronary intervention. We analyzed data from our Intensive Cardiac Care Florence STEMI Registry, comprising 991 STEMI patients consecutively admitted to our intensive cardiac care unit after mechanical revascularization, to assess the clinical impact of both Thrombolysis In Myocardial Infarction (TIMI) and Acute Catheterization and Urgent Intervention Triage Strategy (ACUITY) classifications in identifying patients with major bleeding at higher risk for in-hospital mortality. Major bleeding events occurred in 8.9% of patients (88/991) in the TIMI classification and in 17.2% of patients (170/991) in the ACUITY classification. Among patients with major bleeding classified according to ACUITY, 82 patients did not meet the TIMI criteria for major bleeding. These patients represent the so-called gray zone, where no transfusion was performed and only 1 patient died. In STEMI patients who undergo primary percutaneous coronary intervention and receive dual antiplatelet therapy, TIMI is more capable than ACUITY in identifying patients with major bleeding at higher risk for early mortality. The presence of renal failure represents an independent predictor for major bleeding.

Incidence and clinical consequences of acquired thrombocytopenia after antithrombotic therapies in patients with acute coronary syndromes: Results from the Acute Catheterization and Urgent Intervention Triage Strategy (ACUITY) trial

The aim of the study was to investigate the incidence and clinical consequences of acquired thrombocytopenia in patients with acute coronary syndromes (ACS) in the ACUITY trial. We examined 10,836 patients with ACS randomized to receive heparin plus glycoprotein (GP) IIb/IIIa inhibitor, bivalirudin plus GP IIb/IIIa inhibitor, or bivalirudin monotherapy. Acquired thrombocytopenia developed in 740 (6.8%) patients; mild (100,000-150,000 platelets/mm³), moderate (50,000-100,000 platelets/mm³), and severe (< 50,000 platelets/mm³) developed in 656 (6%), 51 (0.5%), and 33 (0.3%) patients, respectively. Patients with acquired thrombocytopenia, compared with those without, were more likely to develop major bleeding (14% vs 4.3%, P < .0001) at 30 days and had higher rates of mortality (6.5% vs 3.4%, P < .0001) at 1 year. By multivariate analysis, acquired thrombocytopenia was an independent predictor of major bleeding at 30 days (hazard ratio [HR] 1.68, 95% CI 1.04-2.72, P = .03). Moderate and severe acquired thrombocytopenia were predictors of mortality at 1 year (HR 2.89, 95% CI 0.92-9.06, P = .06, and HR 3.41, 95% CI 1.09-10.68, P = .03, respectively). Compared to heparin plus GP IIb/IIIa inhibitor, bivalirudin monotherapy was associated with less declines in platelet count by >25% (7.6% vs 5.6%, P = .0009) and >50% (1.4% vs 0.7%, P = .004) from baseline. Acquired thrombocytopenia occurs in approximately 1 in 14 patients with ACS treated with antithrombin and antiplatelet medications and is strongly associated with hemorrhagic and ischemic complications. Compared to an anticoagulant regimen including a GP IIb/IIIa inhibitor, administration of bivalirudin monotherapy appears to be associated with less frequent declines in platelet count.