Acute Catheterization And Urgent Intervention Triage Strategy Research Articles

Reperfusion After Fibrinolytic Therapy (RAFT): An open-label, multi-centre, randomised controlled trial of bivalirudin versus heparin in rescue percutaneous coronary intervention.

BackgroundThe safety and efficacy profile of bivalirudin has not been examined in a randomised controlled trial of patients undergoing rescue PCI.ObjectivesWe conducted an open-label, multi-centre, randomised controlled trial to compare bivalirudin with heparin ± glycoprotein IIb/IIIa inhibitors (GPIs) in patients undergoing rescue PCI.MethodsBetween 2010–2015, we randomly assigned 83 patients undergoing rescue PCI to bivalirudin (n = 42) or heparin ± GPIs (n = 41). The primary safety endpoint was any ACUITY (Acute Catheterization and Urgent Intervention Triage Strategy) bleeding at 90 days. The primary efficacy endpoint was infarct size measured by peak troponin levels as a multiple of the local upper reference limit (Tn/URL). Secondary endpoints included periprocedural change in haemoglobin adjusted for red cells transfused, TIMI (Thrombolysis in Myocardial Infarction) bleeding, ST-segment recovery and infarct size determined by the Selvester QRS score.ResultsThe trial was terminated due to slow recruitment and futility after an interim analysis of 83 patients. The primary safety endpoint occurred in 6 (14%) patients in the bivalirudin group (4.8% GPIs) and 3 (7.3%) in the heparin ± GPIs group (54% GPIs) (risk ratio, 1.95, 95% confidence interval [CI], 0.52–7.3, P = 0.48). Infarct size was similar between the two groups (mean Tn/URL, 730 [±675] for bivalirudin, versus 984 [±1585] for heparin ± GPIs, difference, 254, 95% CI, -283-794, P = 0.86). There was a smaller decrease in the periprocedural haemoglobin level with bivalirudin than heparin ± GPIs (-7.5% [±15] versus -14% [±17], difference, -6.5%, 95% CI, -0.83–14, P = 0.0067). The rate of complete (≥70%) ST-segment recovery post-PCI was higher in patients randomised to heparin ± GPIs compared with bivalirudin.ConclusionsWhether bivalirudin compared with heparin ± GPI reduces bleeding in rescue PCI could not be determined. Slow recruitment and futility in the context of lower-than-expected bleeding event rates led to the termination of this trial (ANZCTR.org.au, ACTRN12610000152022).

Meta-Analysis of Bleeding Scores Performance for Acute Coronary Syndrome

Bleeding is a common and frequently devastating complication in acute coronary syndrome (ACS). It is critical to evaluate in the current era of ACS management involving invasive strategies and potent anti-thrombotics. Risk models remain under-utilised in this setting but may guide the choice and duration of therapy. We compared their performances for predicting bleeding in ACS patients in this meta-analysis. Medline, EMBASE, Cochrane and Scopus were searched for relevant articles from 1980 to 31 December 2017 assessing external validation of risk scores for bleeding after ACS. Two (2) authors independently reviewed the searched studies for eligibility, followed by pooled analyses using random effects models. Amongst 1,843 articles searched, 73 full-texts were reviewed and 17 studies totalling 18,155 patients were included for analysis. C-statistics (95% confidence interval) for predicting in-hospital major bleeding by risk model were Can Rapid risk stratification of Unstable angina patients Suppress ADverse outcomes with Early implementation of the ACC/AHA guidelines (CRUSADE) 0.714 (0.659-0.779), Acute Catheterization and Urgent Intervention Triage strategY (ACUITY) 0.711 (0.626-0.797), Acute Coronary Treatment and Intervention Outcomes Network (ACTION) 0.767 (0.737-0.797), Global Registry of Acute Coronary Events (GRACE) 0.689 (0.473-0.905) and HAS-BLED 0.636 (0.460-0.812). CRUSADE also predicted bleeding during medium-term follow-up c=0.704 (0.644-0.765). It performed better for radial versus femoral access (c=0.826 and 0.734), invasive versus non-invasive strategy (c=0.752 and 0.625) and similarly for ST elevation myocardial infarction (STEMI) and non-ST elevation myocardial infarction (NSTEMI) (c=0.791 and 0.760). Heterogeneities of studies and paucity of studies assessing risk scores beyond CRUSADE were important limitations. Acute coronary syndrome-specific bleeding scores had moderate discrimination for bleeding, while the GRACE and HAS-BLED scores could not. The ACTION score had the highest pooled c-statistic, while the CRUSADE score was the most widely studied, and also performed better for invasive strategy and radial access subgroups.

Safety and efficacy of bivalirudin monotherapy in patients with non-ST-segment elevation acute coronary syndromes with positive biomarkers undergoing percutaneous coronary intervention: a report from the Acute Catheterization and Urgent Intervention Triage Strategy trial

There are limited data on bivalirudin monotherapy in patients with non-ST-segment elevation acute coronary syndromes (NSTE-ACS) with positive biomarkers of myocardial necrosis (troponin and/or creatine kinase-myocardial band isoenzyme). We sought to evaluate the safety and efficacy of bivalirudin monotherapy in patients with positive biomarkers from the Acute Catheterization and Urgent Intervention Triage Strategy (ACUITY) trial. We compared the net adverse clinical events [composite ischemia - (death, myocardial infarction, or unplanned ischemic revascularization) - or noncoronary artery bypass graft surgery (CABG)-related major bleeding] among patients with biomarker-positive NSTE-ACS in the ACUITY trial overall and by antithrombotic strategy. Among 13 819 patients with NSTE-ACS enrolled in ACUITY, 4728 patients presented with positive biomarkers and underwent an early invasive strategy. Of those, 1547 were randomized to heparin plus a glycoprotein IIb/IIIa inhibitor (GPI), 1555 to bivalirudin plus GPI, and 1626 to bivalirudin monotherapy. Compared with biomarker-negative patients, biomarker-positive patients had higher 30-day rates of net adverse clinical events (14.0 vs. 12.4%; P = 0.04), all-cause death (1.3 vs. 0.5%; P = 0.001), cardiac death (1.1 vs. 0.5%; P = 0.005), and non-CABG-related major bleeding (6.5 vs. 5.2%, P = 0.03). At 30 days, bivalirudin monotherapy was associated with significantly less non-CABG-related major bleeding (bivalirudin monotherapy 4.1% vs. bivalirudin plus GPI 8.4% vs. heparin plus GPI 7.1%) with comparable rates of composite ischemia (bivalirudin monotherapy 9.2% vs. bivalirudin plus GPI 9.9% vs. heparin plus GPI 8.4%). In a multivariable model, bivalirudin monotherapy was associated with a significant reduction in non-CABG-related major bleeding but was not associated with an increased risk of death, myocardial infarction, unplanned revascularization or stent thrombosis. Compared with heparin plus GPI or bivalirudin plus GPI, bivalirudin monotherapy provides similar protection from ischemic events with less major bleeding at 30 days among patients with NSTE-ACS and positive biomarkers.

Standard versus ultrasound-guided radial and femoral access in coronary angiography and intervention (SURF): a randomised controlled trial.

This study aimed to compare outcomes in unselected patients undergoing cardiac catheterisation via transradial versus transfemoral access and standard versus ultrasound-guided arterial access. This was a prospective, randomised (radial vs. femoral and standard vs. ultrasound), 2x2 factorial trial of 1,388 patients undergoing coronary angiography and percutaneous coronary intervention. The primary outcome was a composite of ACUITY (Acute Catheterization and Urgent Intervention Triage strategY) major bleeding, MACE (death, stroke, myocardial infarction or urgent target lesion revascularisation) and vascular complications at 30 days. Transradial access reduced the primary outcome (RR 0.37, 95% CI: 0.17-0.81; p=0.013), mostly driven by ACUITY major bleeding (RR 0.343, 95% CI: 0.123-0.959; p=0.041) when compared with the transfemoral approach. There was no difference in the primary outcome between standard and ultrasound guidance (p=0.76). Ultrasound guidance, however, reduced mean access time (93 sec vs. 111 sec; p=0.009), attempts (1.47 vs. 1.9; p<0.0001), difficult accesses (4.5% vs. 9.2%; p=0.0007), venepuncture (4.1% vs. 9.2%; p<0.0001) and improved first-pass success (73% vs. 59.7%; p<0.0001). Transradial access significantly reduced the composite outcome compared to transfemoral access. Ultrasound guidance did not reduce the primary outcome compared to the standard technique, but significantly improved the efficiency and overall success rate of arterial access.

Cangrelor or Clopidogrel in Patients with Type 2 Diabetes Mellitus Undergoing Percutaneous Coronary Intervention: A Meta-Analysis of Randomized Controlled Trials.

IntroductionWith recent advances in interventional cardiology where percutaneous coronary intervention (PCI) has become the most preferred invasive strategy and with advances in adjunctive pharmacotherapy, several newer oral P2Y12 inhibitors have reached the market. In this analysis, we aimed to compare the cardiovascular outcomes and bleeding events which were associated with the use of cangrelor versus clopidogrel in patients with type 2 diabetes mellitus (T2DM) 48 h after PCI. MethodsThe electronic databases MEDLINE (PubMed), www.ClinicalTrials.gov, EMBASE, and Cochrane central were searched for relevant publications comparing canagrelor with clopidogrel during PCI. Patients with T2DM were extracted. Adverse cardiovascular outcomes and bleeding events at 48 h follow-up were considered as the end points. This meta-analysis was carried out with the latest RevMan software (5.30). Odds ratios (OR) and 95% confidence intervals (CI) were used to represent the data.ResultsThis analysis consisted of a total number of 5031 participants with T2DM (enrolled between the years 2006 and 2012). Compared to clopidgrel, use of cangrelor in these patients with T2DM was not associated with significantly different primary end point (OR 0.94, 95% CI 0.75–1.16; P = 0.55), myocardial infarction (OR 0.96, 95% CI 0.76–1.20; P = 0.71), all-cause death (OR 0.70, 95% CI 0.25–1.96; P = 0.49), ischemia-driven revascularization (OR 0.66, 95% CI 0.32–1.36; P = 0.26), and stent thrombosis (OR 0.45, 95% CI 0.17–1.17; P = 0.10). Thrombolysis in myocardial infarction (TIMI)-defined major and minor bleedings were similarly manifested: (OR 1.02, 95% CI 0.38–2.74; P = 0.96) and (OR 1.39, 95% CI 0.70–2.79; P = 0.35), respectively. Global use of strategies to open occluded arteries (GUSTO)-defined moderate and severe bleeding were also not significantly different: (OR 1.36, 95% CI 0.70–2.67; P = 0.37) and (OR 1.21, 95% CI 0.41–3.59; P = 0.74), respectively. However, GUSTO-defined mild bleeding and acute catheterization and urgent intervention triage strategy (ACUITY)-defined major and minor bleedings were significantly in favor of clopidogrel in comparison to cangrelor in these patients with T2DM: (OR 1.28, 95% CI 1.09–1.50; P = 0.003), (OR 1.43, 95% CI 1.05–1.94; P = 0.02), and (OR 1.23, 95% CI 1.04–1.46; P = 0.02), respectively. Other bleeding outcomes were not significantly different.ConclusionsIn these patients with T2DM, cangrelor was comparable to clopidogrel in terms of efficacy at 48 h following PCI. However, it was associated with significantly higher mild GUSTO bleeding and major and minor ACUITY bleeding, therefore requiring further workups on its safety side. This hypothesis should be explored further and confirmed in other forthcoming trials based strictly on patients with T2DM.

Bleeding Events Before Coronary Angiography in Patients With Non-ST-Segment Elevation Acute Coronary Syndrome

BackgroundUpstream administration of antithrombotic drugs to patients with non–ST-segment elevation acute coronary syndromes before coronary angiography is a common practice despite an incomplete understanding of the risks and benefits. ObjectivesThe authors analyzed the incidence of bleeding and ischemic events occurring before angiography and assessed their association with antithrombotic drugs and mortality risk. MethodsAll patients from the ACUITY (Acute Catheterization and Urgent Intervention Triage Strategy) trial with planned angiography after enrollment were included. Bleeding events were classified according to the ACUITY scale as major or nonmajor bleeding. Kaplan-Meier and Cox proportional hazards analyses were performed. ResultsOf 13,726 patients, 275 (2.0%) bled before angiography, including 52 (0.4%) with major bleeding. Forty-four (0.3%) experienced myocardial infarction. The median time from randomization to coronary angiography was 4.5 h (interquartile ratio [IQR]: 1.7 to 19.7 h) for patients who did not bleed while waiting for angiography and 27.9 h (IQR: 21.9 to 65.6 h) for patients who bled while waiting for angiography (p < 0.001). Bleeding events accrued linearly over time, reaching 10.4% at 96 h post-randomization. Independent predictors of bleeding before angiography included age (adjusted hazard ratio [HR]: 1.03 per year of age; 95% confidence interval [CI]: 1.01 to 1.04; p < 0.001), renal insufficiency (adjusted HR: 1.48; 95% CI: 1.07 to 2.04; p = 0.02), and use of multiple antithrombotic drugs (adjusted HR: 1.33; 95% CI: 1.14 to 1.56; p < 0.001). Bleeding before coronary angiography was associated with longer hospitalization (4.8 days [IQR: 3.0 to 8.9 days] vs. 3.0 days [IQR: 1.9 to 5.9 days]; p < 0.001). Patients who bled before angiography were more likely to die within 1 year than patients who did not bleed (8.5% vs. 4.1%; p < 0.001; adjusted HR: 1.89 (95% CI: 1.23 to 2.90; p = 0.004). ConclusionsUpstream antithrombotic treatment of patients with non–ST-segment elevation acute coronary syndromes awaiting coronary angiography is associated with excess bleeding with mortality implications. Bleeding avoidance strategies before angiogram, including early angiography, may negate the need to prolong upstream antithrombotic treatment and improve the overall risk-benefit balance for these patients. (Acute Catheterization and Urgent Intervention Triage Strategy [ACUITY]; NCT00093158)

The potential cost-effectiveness of the Diamondback 360® Coronary Orbital Atherectomy System for treating de novo, severely calcified coronary lesions: an economic modeling approach.

Background:Patients who undergo percutaneous coronary intervention (PCI) for severely calcified coronary lesions have long been known to have worse clinical and economic outcomes than patients with no or mildly calcified lesions. We sought to assess the likely cost-effectiveness of using the Diamondback 360® Orbital Atherectomy System (OAS) in the treatment of de novo, severely calcified lesions from a health-system perspective.Methods and results:In the absence of a head-to-head trial and long-term follow up, cost-effectiveness was based on a modeled synthesis of clinical and economic data. A cost-effectiveness model was used to project the likely economic impact. To estimate the net cost impact, the cost of using the OAS technology in elderly (⩾ 65 years) Medicare patients with de novo severely calcified lesions was compared with cost offsets. Elderly OAS patients from the ORBIT II trial (Evaluate the Safety and Efficacy of OAS in Treating Severely Calcified Coronary Lesions) [ClinicalTrials.gov identifier: NCT01092426] were indirectly compared with similar patients using observational data. For the index procedure, the comparison was with Medicare data, and for both revascularization and cardiac death in the following year, the comparison was with a pooled analysis of the Harmonizing Outcomes with Revascularization and Stents in Acute Myocardial Infarction (HORIZONS-AMI)/Acute Catheterization and Urgent Intervention Triage Strategy (ACUITY) trials. After adjusting for differences in age, gender, and comorbidities, the ORBIT II mean index procedure costs were 17% (p < 0.001) lower, approximately US$2700. Estimated mean revascularization costs were lower by US$1240 in the base case. These cost offsets in the first year, on average, fully cover the cost of the device with an additional 1.2% cost savings. Even in the low-value scenario, the use of the OAS is cost-effective with a cost per life-year gained of US$11,895.Conclusions:Based on economic modeling, the recently approved coronary OAS device is projected to be highly cost-effective for patients who undergo PCI for severely calcified lesions.

Incremental Value of the CRUSADE, ACUITY, and HAS-BLED Risk Scores for the Prediction of Hemorrhagic Events After Coronary Stent Implantation in Patients Undergoing Long or Short Duration of Dual Antiplatelet Therapy.

BackgroundMultiple scores have been proposed to stratify bleeding risk, but their value to guide dual antiplatelet therapy duration has never been appraised. We compared the performance of the CRUSADE (Can Rapid Risk Stratification of Unstable Angina Patients Suppress Adverse Outcomes With Early Implementation of the ACC/AHA Guidelines), ACUITY (Acute Catheterization and Urgent Intervention Triage Strategy), and HAS‐BLED (Hypertension, Abnormal Renal/Liver Function, Stroke, Bleeding History or Predisposition, Labile INR, Elderly, Drugs/Alcohol Concomitantly) scores in 1946 patients recruited in the Prolonging Dual Antiplatelet Treatment After Grading Stent‐Induced Intimal Hyperplasia Study (PRODIGY) and assessed hemorrhagic and ischemic events in the 24‐ and 6‐month dual antiplatelet therapy groups.Methods and ResultsBleeding score performance was assessed with a Cox regression model and C statistics. Discriminative and reclassification power was assessed with net reclassification improvement and integrated discrimination improvement. The C statistic was similar between the CRUSADE score (area under the curve 0.71) and ACUITY (area under the curve 0.68), and higher than HAS−BLED (area under the curve 0.63). CRUSADE, but not ACUITY, improved reclassification (net reclassification index 0.39, P=0.005) and discrimination (integrated discrimination improvement index 0.0083, P=0.021) of major bleeding compared with HAS‐BLED. Major bleeding and transfusions were higher in the 24‐ versus 6‐month dual antiplatelet therapy groups in patients with a CRUSADE score >40 (hazard ratio for bleeding 2.69, P=0.035; hazard ratio for transfusions 4.65, P=0.009) but not in those with CRUSADE score ≤40 (hazard ratio for bleeding 1.50, P=0.25; hazard ratio for transfusions 1.37, P=0.44), with positive interaction (P int=0.05 and P int=0.01, respectively). The number of patients with high CRUSADE scores needed to treat for harm for major bleeding and transfusion were 17 and 15, respectively, with 24‐month rather than 6‐month dual antiplatelet therapy; corresponding figures in the overall population were 67 and 71, respectively.ConclusionsOur analysis suggests that the CRUSADE score predicts major bleeding similarly to ACUITY and better than HAS BLED in an all‐comer population with percutaneous coronary intervention and potentially identifies patients at higher risk of hemorrhagic complications when treated with a long‐term dual antiplatelet therapy regimen.Clinical Trial Registration URL: http://clinicaltrials.gov. Unique identifier: NCT00611286.

Incidence and impact of acute kidney injury in patients with acute coronary syndromes treated with coronary artery bypass grafting: Insights from the Harmonizing Outcomes With Revascularization and Stents in Acute Myocardial Infarction (HORIZONS-AMI) and Acute Catheterization and Urgent Intervention Triage Strategy (ACUITY) trials

Acute kidney injury (AKI) is a well-recognized predictor of morbidity and mortality after percutaneous coronary intervention. However, the impact of AKI on the outcome of patients with acute coronary syndromes (ACS) in relation to coronary artery bypass grafting (CABG) has not been established. Of the 17,421 patients who presented with non-ST-segment elevation ACS or ST-segment elevation myocardial infarction enrolled in the ACUITY and HORIZONS-AMI trials, 1,406 (8.0%) underwent CABG as principal treatment after coronary angiography. End points were measured at 1 month and 1 year and included death, myocardial infarction, and ischemia-driven target vessel revascularization. Acute kidney injury was defined as a rise in creatinine of ≥ 0.5 mg/dL, or > 25%, from baseline at initial angiography. Acute kidney injury occurred during hospital admission in 449 (31.9%) of the 1,406 patients treated with CABG. One-month and 1-year mortality was 6.7% vs 2.2% (P < .0001) and 10.4% vs 4.3% (P < .0001) for patients with vs without AKI, respectively. Analogously, the 1-month and 1-year incidence of composite major adverse cardiac events (MACEs; death, MI, or target vessel revascularization) was 17.6% vs 12.4% (P = .003) and 22.0% vs 15.3% (P = .002) for patients with vs without AKI, respectively. After adjustment for age, sex, race, diabetes, hypertension, and baseline creatinine clearance, AKI was an independent predictor of mortality (overall and cardiac-related) and MACE at both 1 month and 1 year in patients treated with CABG. Acute kidney injury occurred in approximately 1 of every 3 patients with ACS treated with CABG and is a powerful independent predictor of death and MACE. These data highlight the need for AKI prevention strategies in patients undergoing CABG.

Effect of Baseline Thrombocytopenia on Ischemic Outcomes in Patients With Acute Coronary Syndromes Who Undergo Percutaneous Coronary Intervention

BackgroundAcquired thrombocytopenia (TP) has been associated with short- and long-term adverse outcomes after percutaneous coronary intervention (PCI), but the role of baseline TP is less well defined. We sought to evaluate the effect of TP on long-term adverse outcomes in patients with acute coronary syndromes (ACS) who undergo PCI. MethodsData from 10,603 patients who underwent PCI for non-ST-elevation ACS or ST-elevation myocardial infarction were pooled from 2 large-scale randomized trials, Acute Catheterization and Urgent Intervention Triage Strategy (ACUITY) and Harmonizing Outcomes With Revascularization and Stents in Acute Myocardial Infarction (HORIZONS-AMI). Patients were stratified according to baseline platelet counts. Those with platelet counts <150,000/mm3 were considered to have normal platelet counts. Adverse event rates were compared between groups with and without multivariable adjustment. ResultsBaseline TP was present in 607 (5.7%) patients. The unadjusted 1-year rates of death (6.7% vs 3.6%; P < 0.0001), occurrence of major adverse cardiac event (MACE) (20.8% vs 15.6%; P = 0.0002), and target lesion revascularization (TLR; 9.4% vs 7.2%; P = 0.01) were significantly higher in patients with baseline TP compared with patients with normal platelet counts. By multivariable analysis, the presence of TP at baseline was an independent predictor of 1-year death (hazard ratio [HR], 1.74; 95% confidence interval [CI], 1.12-2.69; P = 0.01), ischemic TLR (HR, 1.37; 95% CI, 1.04-1.81; P = 0.03), and MACE (HR, 1.39; 95% CI, 1.09-1.79; P = 0.009). ConclusionsThe presence of baseline TP in the setting of ACS patients who undergo PCI was strongly predictive of death, ischemic TLR, and MACE at 1 year. Baseline TP might be a useful baseline clinical parameter to estimate future ischemic risk after PCI.

Effect of Anemia on Frequency of Short- and Long-Term Clinical Events in Acute Coronary Syndromes (from the Acute Catheterization and Urgent Intervention Triage Strategy Trial)

There are limited data on the impact of anemia on clinical outcomes in unstable angina and non-ST-segment elevation myocardial infarction treated with an early invasive strategy. We sought to determine the short- and long-term clinical events among patients with and without anemia enrolled in the Acute Catheterization and Urgent Intervention Triage Strategy (ACUITY) trial. Anemia was defined as baseline hemoglobin of <13g/dl for men and <12g/dl for women. The primary end points were composite ischemia (death, myocardial infarction, or unplanned revascularization for ischemia) and major bleeding assessed in-hospital, at 1 month, and at 1 year. Among the 13,819 patients in the ACUITY trial, information regarding anemia was available in 13,032 (94.3%), 2,199 of whom (16.9%) had anemia. Patients with anemia compared with those without anemia had significantly increased adverse event rates in-hospital (composite ischemia 6.6% vs 4.8%, p= 0.0004; major bleeding 7.3% vs 3.3%, p<0.0001), at 1 month (composite ischemia 10% vs 7.2%, p <0.0001, major bleeding 8.8% vs 3.9%, p <0.0001), and 1 year (composite ischemia 21.7% vs 15.3%, p <0.0001). Anemia was an independent predictor of death at 1 year (hazard ratio 1.77, 95% confidence interval [CI] 1.29 to 2.44, p= 0.0005). Composite ischemia was significantly more common among patients who developed in-hospital non-coronary artery bypass surgery major bleeding compared with those who did not (anemic patients 1-year relative risk 2.19, 95% CI 1.67 to 2.88, p <0.0001; nonanemic patients relative risk 2.16, 95% CI 1.76 to 2.65, p <0.0001). In conclusion, in the ACUITY trial, baseline anemia was strongly associated with adverse earlyand late clinical events, especially in those who developed major bleeding.

Impact of Cigarette Smoking on Extent of Coronary Artery Disease and Prognosis of Patients With Non–ST-Segment Elevation Acute Coronary Syndromes: An Analysis From the ACUITY Trial (Acute Catheterization and Urgent Intervention Triage Strategy)

This study sought to evaluate the short- and long-term outcomes for smokers with non-ST-segment elevation acute coronary syndromes (NSTE-ACS). Smoking has been associated with the "paradox" of reduced mortality after acute myocardial infarction (MI). This is thought to be due to favorable baseline characteristics and less diffuse coronary artery disease (CAD) among smokers. In the ACUITY (Acute Catheterization and Urgent Intervention Triage Strategy) trial, 13,819 patients (29.1% smokers) with moderate- to high-risk NSTE-ACS underwent angiography and, if indicated, revascularization. Smokers were significantly younger and had fewer comorbidities than nonsmokers. Incidence of death and MI were comparable at 30 days, although smokers had significantly reduced risks of 30-day major bleeding (hazard ratio [HR]: 0.80, 95% confidence interval [CI]: 0.67 to 0.96; p = 0.016) and 1-year mortality (HR: 0.797, 95% CI: 0.65 to 0.97; p = 0.027). After correction for baseline and clinical differences, smoking was no longer predictive of major bleeding (odds ratio: 1.06, 95% CI: 0.86 to 1.32; p = 0.56) and was associated with higher 1-year mortality (HR: 1.37, 95% CI: 1.07 to 1.7; p = 0.013). This pattern of reversed risk after multivariable correction held true for those smokers requiring percutaneous coronary intervention. Core laboratory angiographic analysis showed that smokers and nonsmokers were comparable in terms of the extent of CAD, Thrombolysis In Myocardial Infarction flow, myocardial blush, and the presence of thrombi. In contrast to the paradox previously described in ST-segment elevation MI, our analysis finds smoking to be an independent predictor of higher 1-year mortality in patients presenting with NSTE-ACS, and our angiographic study demonstrates CAD in smokers that is comparable to that in nonsmokers but evident ∼1 decade earlier. (Acute Catheterization and Urgent Intervention Triage Strategy [ACUITY]; NCT00093158).

Impact of Nonculprit Vessel Myocardial Perfusion on Outcomes of Patients Undergoing Percutaneous Coronary Intervention for Acute Coronary Syndromes: Analysis From the ACUITY Trial (Acute Catheterization and Urgent Intervention Triage Strategy)

This study evaluated the impact of nonculprit vessel myocardial perfusion on outcomes of non-ST-segment elevation acute coronary syndromes (NSTE-ACS) patients. ST-segment elevation myocardial infarction patients have decreased perfusion in areas remote from the infarct-related vessel. The impact of myocardial hypoperfusion of regions supplied by nonculprit vessels in NSTE-ACS patients treated with percutaneous coronary intervention (PCI) is unknown. The angiographic substudy of the ACUITY (Acute Catheterization and Urgent Intervention Triage Strategy) trial included 6,921 NSTE-ACS patients. Complete 3-vessel assessments of baseline coronary TIMI (Thrombolysis In Myocardial Infarction) flow grade and myocardial blush grade (MBG) were performed. We examined the outcomes of PCI-treated patients according to the worst nonculprit vessel MBG identified per patient. Among the 3,826 patients treated with PCI, the worst nonculprit MBG was determined in3,426 (89.5%) patients, including 375 (10.9%) MBG 0/1 patients, 475 (13.9%) MBG 2 patients, and 2,576 (75.2%) MBG 3 patients. Nonculprit MBG 0/1 was associated with worse baseline clinical characteristics. Patients with nonculprit MBG 0/1 versus MBG 3 had increased rates of 30-day (3.0% vs.0.7%, p < 0.0001) and 1-year (4.4% vs. 1.0%, p < 0.0001) death. Similar results were found among patients with pre-procedural TIMI flow grade 3 in the culprit vessel, where nonculprit vessel MBG 0/1 (hazard ratio: 2.81 [95% confidence interval: 1.63 to 4.84], p= 0.0002) was the strongest predictor of 1-year mortality. Reduced myocardial perfusion in an area supplied by a nonculprit vessel is associated with increased short- and long-term mortality rates in NSTE-ACS patients undergoing PCI. Furthermore, worst nonculprit MBG is able to risk-stratify patients with normal baseline flow of the culprit vessel.

Ischemic Outcomes After Coronary Intervention of Calcified Vessels in Acute Coronary Syndromes: Pooled Analysis From the HORIZONS-AMI (Harmonizing Outcomes With Revascularization and Stents in Acute Myocardial Infarction) and ACUITY (Acute Catheterization and Urgent Intervention Triage Strategy) Trials

This study sought to determine the frequency and impact of coronary calcification among patients undergoing percutaneous coronary intervention (PCI) for acute coronary syndromes (ACS).Small studies in patients with stable coronary artery disease have suggested a worse prognosis after PCI of calcified compared with noncalcified lesions. Little is known about the impact of coronary calcification on outcomes after PCI for patients presenting with non-ST-segment elevation and ST-segment elevation ACS.Data from 6,855 patients presenting with ACS in whom PCI was performed were pooled from 2 large-scale randomized, controlled trials, ACUITY (Acute Catheterization and Urgent Intervention Triage Strategy) and HORIZONS-AMI (Harmonizing Outcomes With Revascularization and Stents in Acute Myocardial Infarction). One-year outcomes were analyzed according to the severity of PCI target lesion calcification (none/mild, moderate, or severe) as assessed by an independent angiographic core laboratory.Target lesion calcification was severe in 402 patients (5.9%), moderate in 1,788 (26.1%), and none/mild in 4,665 (68.1%). Moderate/severe target lesion calcification was more frequent in older patients, men, hypertensive patients, and those presenting with ST-segment elevation myocardial infarction (STEMI). The unadjusted 1-year rates of death, cardiac death, definite stent thrombosis, and ischemic target lesion revascularization (TLR) and target vessel revascularization were significantly increased in patients with moderate/severe target lesion calcification. By multivariable analysis, the presence of moderate/severe target lesion calcification was an independent predictor of 1-year definite stent thrombosis (hazard ratio [HR]: 1.62; 95% confidence interval [CI]: 1.14 to 2.30; p = 0.007) and ischemic TLR (HR: 1.44; 95% CI: 1.17 to 1.78; p = 0.0007).Moderate/severe lesion calcification was relatively frequent in patients with non-ST-segment elevation ACS and STEMI and was strongly predictive of stent thrombosis and ischemic TLR at 1 year. (Comparison of Angiomax Versus Heparin in Acute Coronary Syndromes [ACS]; NCT00093158; Harmonizing Outcomes With Revascularization and Stents in Acute Myocardial Infarction; NCT00433966).

Comparative effectiveness of upstream glycoprotein IIb/IIIa inhibitors in patients with moderate- and high-risk acute coronary syndromes: An Acute Catheterization and Urgent Intervention Triage Strategy (ACUITY) substudy

Tirofiban and eptifibatide are both small-molecule, competitive glycoprotein IIb/IIIa receptor inhibitors (GPIs) that are guideline-supported for upstream therapy in acute coronary syndromes (ACS). This study sought to compare the efficacy and safety of tirofiban and eptifibatide in patients with ACS. Within the ACUITY trial, 4,323 patients with moderate- and high-risk ACS received upstream, adjunctive GPI (tirofiban or eptifibatide) in addition to an antithrombin. Primary outcomes included 30-day rates of composite major adverse cardiac events (MACE), major bleeding (not related to coronary artery bypass grafting), and composite net adverse clinical events (NACE). The outcomes were compared based on the upstream GPI administered. There were significant differences in the baseline characteristics of patients treated with tirofiban vs eptifibatide, particularly related to country/region. In unadjusted analyses, treatment with upstream tirofiban vs eptifibatide was associated with similar rates of major bleeding (5.8% vs 6.5%, P = .39) and nonsignificantly lower rates of MACE (6.1% vs 7.6%, P = .06) and NACE (10.6% vs 12.6%, P = .06). After propensity-based multivariable adjustment, there were no significant differences between tirofiban and eptifibatide with respect to 30-day major bleeding, MACE, or NACE. Among more than 4,000 patients with moderate- and high-risk ACS treated with upstream GPI as part of an early invasive management strategy, the use of tirofiban and eptifibatide resulted in similar clinical outcomes. These data suggest equivalence of these 2 agents for upstream use, while highlighting some of the difficulties of nonrandomized comparative effectiveness analyses, specifically the difficulty in addressing geographic differences in the use of nonrandomized treatments.

Association Between Intraprocedural Thrombotic Events and Adverse Outcomes After Primary Percutaneous Coronary Intervention for ST-Segment Elevation Myocardial Infarction (a Harmonizing Outcomes With RevasculariZatiON and Stents in Acute Myocardial Infarction [HORIZONS-AMI] Substudy)

The present study sought to determine the extent to which adverse angiographic events encountered during percutaneous coronary intervention for ST-segment elevation myocardial infarction (STEMI) are associated with adverse clinical outcomes. Patients with STEMI represent a cohort at particularly high risk of intraprocedural thrombotic events (IPTEs). The overall frequency and implications of IPTEs occurring in patients with STEMI have not been systematically quantified in previous studies. A total of 3,163 patients undergoing primary percutaneous coronary intervention with stent implantation for STEMI in the Harmonizing Outcomes with RevasculariZatiON and Stents in Acute Myocardial Infarction (HORIZONS-AMI) trial underwent detailed frame-by-frame core laboratory angiographic analysis to assess IPTEs. The clinical outcomes at 30 days were compared between the patients with and without IPTEs. IPTEs, defined as the development of new or increasing thrombus, abrupt vessel closure, no reflow, slow reflow, and distal embolization at any point during the procedure, occurred in 386 patients (12.2%). The independent predictors of IPTE were thrombus at baseline, lesion length, and randomization to bivalirudin; the patients with IPTEs were also more likely to receive bailout glycoprotein IIb/IIIa inhibitors and unplanned thrombectomy. Compared with patients without IPTEs, the patients with IPTEs had higher 30-day rates of composite major adverse cardiovascular events (death, myocardial infarction, ischemic target vessel revascularization, and stroke; 7.8% vs 4.2%, p = 0.002), major bleeding not related to coronary artery bypass grafting (11.8% vs 6.5%, p <0.001), and all-cause death (4.2% vs 1.8%, p = 0.002). On multivariate analysis, IPTEs were independently associated with 30-day major adverse cardiovascular events, major bleeding, and death. In conclusion, the development of IPTEs in patients undergoing primary percutaneous coronary intervention for STEMI was associated with subsequent adverse outcomes, including major adverse cardiovascular events, major bleeding, and death. Additional studies of strategies to decrease the occurrence of IPTEs are warranted.

TCT-57 Impact Of Coronary Artery Calcification On Clinical Events In Patients Undergoing Coronary Artery Bypass Grafting: Analysis From The ACUITY (Acute Catheterization And Urgent Intervention Triage Strategy) Trial

TCT-57 Impact Of Coronary Artery Calcification On Clinical Events In Patients Undergoing Coronary Artery Bypass Grafting: Analysis From The ACUITY (Acute Catheterization And Urgent Intervention Triage Strategy) Trial

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Prediction of 1-Year Mortality in Patients With Acute Coronary Syndromes Undergoing Percutaneous Coronary Intervention: Validation of the Logistic Clinical SYNTAX (Synergy Between Percutaneous Coronary Interventions With Taxus and Cardiac Surgery) Score

This study sought to validate the Logistic Clinical SYNTAX (Synergy Between Percutaneous Coronary Intervention With Taxus and Cardiac Surgery) score in patients with non-ST-segment elevation acute coronary syndromes (ACS), in order to further legitimize its clinical application. The Logistic Clinical SYNTAX score allows for an individualized prediction of 1-year mortality in patients undergoing contemporary percutaneous coronary intervention. It is composed of a "Core" Model (anatomical SYNTAX score, age, creatinine clearance, and left ventricular ejection fraction), and "Extended" Model (composed of an additional 6 clinical variables), and has previously been cross validated in 7 contemporary stent trials (>6,000 patients). One-year all-cause death was analyzed in 2,627 patients undergoing percutaneous coronary intervention from the ACUITY (Acute Catheterization and Urgent Intervention Triage Strategy) trial. Mortality predictions from the Core and Extended Models were studied with respect to discrimination, that is, separation of those with and without 1-year all-cause death (assessed by the concordance [C] statistic), and calibration, that is, agreement between observed and predicted outcomes (assessed with validation plots). Decision curve analyses, which weight the harms (false positives) against benefits (true positives) of using a risk score to make mortality predictions, were undertaken to assess clinical usefulness. In the ACUITY trial, the median SYNTAX score was 9.0 (interquartile range 5.0 to 16.0); approximately 40% of patients had 3-vessel disease, 29% diabetes, and 85% underwent drug-eluting stent implantation. Validation plots confirmed agreement between observed and predicted mortality. The Core and Extended Models demonstrated substantial improvements in the discriminative ability for 1-year all-cause death compared with the anatomical SYNTAX score in isolation (C-statistics: SYNTAX score: 0.64, 95% confidence interval [CI]: 0.56 to 0.71; Core Model: 0.74, 95% CI: 0.66 to 0.79; Extended Model: 0.77, 95% CI: 0.70 to 0.83). Decision curve analyses confirmed the increasing ability to correctly identify patients who would die at 1 year with the Extended Model versus the Core Model versus the anatomical SYNTAX score, over a wide range of thresholds for mortality risk predictions. Compared to the anatomical SYNTAX score alone, the Core and Extended Models of the Logistic Clinical SYNTAX score more accurately predicted individual 1-year mortality in patients presenting with non-ST-segment elevation acute coronary syndromes undergoing percutaneous coronary intervention. These findings support the clinical application of the Logistic Clinical SYNTAX score.

Paradigm Has Already Shifted to Ischemia-Guided Functional Approach

The anatomic Synergy Between Percutaneous Coronary Intervention With TAXUS and Cardiac Surgery (SYNTAX) score is a stratification score illustrating the complexity of angiographic stenosis. It was considered a surrogate for poor prognosis after percutaneous coronary intervention (PCI).1 Accordingly, in patients with a high baseline SYNTAX score (bSS) requiring coronary revascularization, coronary artery bypass graft surgery was chosen over PCI in the current guidelines.2,3 The mechanism by which bSS is a good surrogate for long-term prognosis is evident. Patients with a high bSS compared with those with a low bSS have more complex comorbidities such as old age, diabetes mellitus, multiple stenoses, and low left ventricular function. Subsequently, they receive more complex procedures using multiple stents and devices. Since the SYNTAX score II was revised by taking into consideration clinical risk factors, the function of the scoring model in choosing between PCI and coronary artery bypass graft surgery and prognosis prediction has improved.4 Article see p 141 The residual SYNTAX score (rSS), which is a variant of the SYNTAX score, was recently constructed to represent the extent of untreated coronary lesions after revascularization treatment. In the Acute Catheterization and Urgent Intervention Triage Strategy (ACUITY) study, comprising patients with acute coronary syndrome, there was a stepwise increase in the rate of major adverse cardiac events, including death, myocardial infarction, and unplanned revascularization, in patients with an rSS of 0 (16.3%), >0 to 2 (18.0%), >2 to 8 (20.0%), and >8 (22.4%).5 In particular, for patients with …