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Background The healthcare burden posed by the coronavirus disease 2019 (COVID‐19) pandemic in the New York Metropolitan area has necessitated the postponement of elective procedures resulting in a marked reduction in cardiac catheterization laboratory (CCL) volumes with a potential to impact interventional cardiology (IC) fellowship training. Methods We conducted a web‐based survey sent electronically to 21 Accreditation Council for Graduate Medical Education accredited IC fellowship program directors (PDs) and their respective fellows. Results Fourteen programs (67%) responded to the survey and all acknowledged a significant decrease in CCL procedural volumes. More than half of the PDs reported part of their CCL being converted to inpatient units and IC fellows being redeployed to COVID‐19 related duties. More than two‐thirds of PDs believed that the COVID‐19 pandemic would have a moderate (57%) or severe (14%) adverse impact on IC fellowship training, and 21% of the PDs expected their current fellows' average percutaneous coronary intervention (PCI) volume to be below 250. Of 25 IC fellow respondents, 95% expressed concern that the pandemic would have a moderate (72%) or severe (24%) adverse impact on their fellowship training, and nearly one‐fourth of fellows reported performing fewer than 250 PCIs as of March 1st. Finally, roughly one‐third of PDs and IC fellows felt that there should be consideration of an extension of fellowship training or a period of early career mentorship after fellowship. Conclusions The COVID‐19 pandemic has caused a significant reduction in CCL procedural volumes that is impacting IC fellowship training in the NY metropolitan area. These results should inform professional societies and accreditation bodies to offer tailored opportunities for remediation of affected trainees.

BACKGROUND: The initial wave of the coronavirus disease 2019 (COVID-19) pandemic resulted in an influx of patients with acute viral illness and profound changes in healthcare delivery in New York City. The impact of this pandemic on the presentation and invasive management of acute myocardial infarction (MI) is not well described. METHODS: This single-center retrospective study compared patients with MI who underwent invasive coronary angiography at NYU in March-April 2020, during the peak of the first wave of the pandemic, to those presenting in March-April 2019. RESULTS: Only 35 patients with MI underwent angiography during the study period in 2020 versus 109 in 2019. No differences in comorbidities or baseline medications were identified. The proportion of patients with ST segment elevation MI (STEMI) was higher in 2020 (48.6% vs. 24.8% in 2019, p = 0.014). Median peak troponin concentration was higher (14.5 vs. 2.9 ng/mL, p = 0.005) and left ventricular ejection fraction was lower (43.34% vs. 51.1%, p = 0.015) during the pandemic. Among patients with non-STEMI, time from symptom onset to presentation was delayed in 2020 compared to 2019 (median 24 hours versus 10 hours, p = 0.04). CONCLUSION: There was a dramatic decrease in the number of patients with MI undergoing coronary angiography during the first wave of the COVID-19 pandemic. Of those that presented, patients tended to seek care later after symptom onset and had excess myocardial injury. These data indicate a need for improved patient education to ensure timely cardiovascular care during public health emergencies.

Background: Vascular injury and inflammation during percutaneous coronary intervention (PCI) are associated with increased risk of post-PCI adverse outcomes. Colchicine decreases neutrophil recruitment to sites of vascular injury. The anti-inflammatory effects of acute colchicine administration before PCI on subsequent myocardial injury are unknown. Methods: In a prospective, single-site trial, subjects referred for possible PCI (n=714) were randomized to acute preprocedural oral administration of colchicine 1.8 mg or placebo. Results: Among the 400 subjects who underwent PCI, the primary outcome of PCI-related myocardial injury did not differ between colchicine (n=206) and placebo (n=194) groups (57.3% versus 64.2%, P =0.19). The composite outcome of death, nonfatal myocardial infarction, and target vessel revascularization at 30 days (11.7% versus 12.9%, P =0.82), and the outcome of PCI-related myocardial infarction defined by the Society for Cardiovascular Angiography and Interventions (2.9% versus 4.7%, P =0.49) did not differ between colchicine and placebo groups. Among 280 PCI subjects in a nested inflammatory biomarker substudy, the primary biomarker end point, change in interleukin-6 concentrations did not differ between groups 1-hour post-PCI but increased less 24 hours post-PCI in the colchicine (n=141) versus placebo group (n=139; 76% [−6 to 898] versus 338% [27 to 1264], P =0.02). High-sensitivity C-reactive protein concentration also increased less after 24 hours in the colchicine versus placebo groups (11% [−14 to 80] versus 66% [1 to 172], P =0.001). Conclusions: Acute preprocedural administration of colchicine attenuated the increase in interleukin-6 and high-sensitivity C-reactive protein concentrations after PCI when compared with placebo but did not lower the risk of PCI-related myocardial injury. Registration: URL: https://www.clinicaltrials.gov ; Unique Identifiers: NCT02594111, NCT01709981.

Background: Contemporary second-generation drug-eluting stents (DES) have superior efficacy and safety in comparison with early-generation stents in patients undergoing percutaneous coronary intervention, in part, related to their thinner struts. Whether newer-generation ultrathin DES further improve clinical outcomes in comparison with older second-generation thicker strut DES is unknown. Methods: We searched PubMed, Embase, and Cochrane Central Register of Controlled Trials for randomized clinical trials that compared newer-generation ultrathin strut DES (defined as strut thickness Results: We identified 10 trials that randomly assigned 11 658 patients and evaluated 3 newer-generation ultrathin strut DES: Orsiro stent (60 μm), MiStent (64 μm), and BioMime (65 µm). In comparison with thicker strut second-generation DES, newer-generation ultrathin strut DES were associated with a 16% reduction in target lesion failure (relative risk, 0.84; 95% CI, 0.72–0.99) driven by less myocardial infarction (relative risk, 0.80; 95% CI, 0.65–0.99). Ultrathin strut DES were also associated with qualitatively lower rates of any stent thrombosis (relative risk, 0.72; 95% CI, 0.51–1.01). Tests for subgroup effects based on the ultrathin strut DES type ( P =0.58) and the comparator DES type ( P =0.98) were not significant, suggesting consistent outcomes across the 3 ultrathin strut DES and with the different DES comparators. Conclusions: In patients undergoing percutaneous coronary intervention, newer-generation ultrathin strut DES further improve 1-year clinical outcomes in comparison with contemporary thicker strut second-generation DES.

Background The extent of coronary disease affects clinical outcomes and may predict the effectiveness of coronary revascularization with either coronary artery bypass graft (CABG) surgery or percutaneous coronary intervention (PCI). The SYNTAX (Synergy Between Percutaneous Coronary Intervention With Taxus and Cardiac Surgery) score quantifies the extent of coronary disease. Objectives This study sought to determine whether SYNTAX scores predicted outcomes and the effectiveness of coronary revascularization compared with medical therapy in the BARI-2D (Bypass Angioplasty Revascularization Investigation 2 Diabetes) trial. Methods Baseline SYNTAX scores were retrospectively calculated for BARI-2D patients without prior revascularization (N = 1,550) by angiographic laboratory investigators masked to patient characteristics and outcomes. The primary outcome was major cardiovascular events (a composite of death, myocardial infarction, and stroke) over 5 years. Results A mid/high SYNTAX score (≥23) was associated with a higher risk of major cardiovascular events (hazard ratio: 1.36, confidence interval: 1.07 to 1.75, p = 0.01). Patients in the CABG stratum had significantly higher SYNTAX scores: 36% had mid/high SYNTAX scores compared with 13% in the PCI stratum (p Conclusions Among patients with diabetes and stable ischemic heart disease, higher SYNTAX scores predict higher rates of major cardiovascular events and were associated with more favorable outcomes of revascularization compared with medical therapy among patients suitable for CABG. (Bypass Angioplasty Revascularization Investigation in Type 2 Diabetes; NCT00006305)

Optimal antithrombotic pharmacotherapy in patients affected by diabetes mellitus (DM) undergoing percutaneous coronary intervention is unclear. We sought to evaluate the safety and efficacy of bivalirudin compared with heparin plus a glycoprotein IIb/IIIa inhibitor (GPI) in patients with DM undergoing percutaneous coronary intervention. We pooled patient-level data from the Randomized Evaluation of PCI Linking Angiomax to Reduced Clinical Events-2, Acute Catheterization and Urgent Intervention Triage strategy, and Harmonizing Outcomes with Revascularization and Stents in Acute Myocardial Infarction trials. The primary efficacy end point was the incidence of major adverse cardiac events, defined as the composite of death, myocardial infarction, or unplanned revascularization at 30 days. The primary safety end point was the incidence of 30-day non–coronary artery bypass graft-related major bleeding. All-cause mortality was reported at 30 days and 1 year. Of the 14,737 patients included in the pooled database, 3,641 (24.7%) had DM. Patients with DM had higher rates of 30-day major bleeding and 30-day and 1-year all-cause mortality. There were no differences in 30-day major adverse cardiac events between bivalirudin versus heparin plus GPI in patients with DM (6.9% vs 7.8%; relative risk [RR] 0.89, 95% CI 0.71 to 1.12) or without DM (7.5% vs 6.7%; RR 1.11, 95% CI 0.97 to 1.27; p interaction = 0.10). Bivalirudin treatment was associated with reduced risk of major bleeding in similar magnitude in patients with DM (4.3% vs 6.6% RR 0.68, 95% CI 0.51 to 0.89) or without DM (3.2% vs 6.1%; RR 0.51, 95% CI 0.43 to 0.61; p interaction = 0.15). The hemorrhagic benefit of bivalirudin was noted for both access site- and non–access site-related bleeding. Overall, bivalirudin treatment was associated with a significant 1-year mortality benefit (2.7% vs 3.3%; RR 0.82, 95% CI 0.68 to 0.98; p = 0.03), which was consistent between patients with or without DM (p interaction = 0.30). In conclusion, compared with heparin plus GPI, bivalirudin was associated with similar 30-day antithrombotic efficacy and better 30-day freedom from bleeding and 1-year mortality, irrespective of diabetic status.

Contemporary second-generation drug-eluting stents (DES) have superior efficacy and safety in comparison with early-generation stents in patients undergoing percutaneous coronary intervention, in part, related to their thinner struts. Whether newer-generation ultrathin DES further improve clinical outcomes in comparison with older second-generation thicker strut DES is unknown.We searched PubMed, Embase, and Cochrane Central Register of Controlled Trials for randomized clinical trials that compared newer-generation ultrathin strut DES (defined as strut thickness70 µm) versus thicker strut second-generation DES and reported clinical outcomes. The primary outcome was target lesion failure (composite of cardiovascular death, target vessel myocardial infarction or ischemia-driven target lesion revascularization) evaluated at 1-year follow-up. Tests for subgroup effects based on the ultrathin strut DES type and the comparator DES type were performed by using meta-regression analysis.We identified 10 trials that randomly assigned 11 658 patients and evaluated 3 newer-generation ultrathin strut DES: Orsiro stent (60 μm), MiStent (64 μm), and BioMime (65 µm). In comparison with thicker strut second-generation DES, newer-generation ultrathin strut DES were associated with a 16% reduction in target lesion failure (relative risk, 0.84; 95% CI, 0.72-0.99) driven by less myocardial infarction (relative risk, 0.80; 95% CI, 0.65-0.99). Ultrathin strut DES were also associated with qualitatively lower rates of any stent thrombosis (relative risk, 0.72; 95% CI, 0.51-1.01). Tests for subgroup effects based on the ultrathin strut DES type ( P=0.58) and the comparator DES type ( P=0.98) were not significant, suggesting consistent outcomes across the 3 ultrathin strut DES and with the different DES comparators.In patients undergoing percutaneous coronary intervention, newer-generation ultrathin strut DES further improve 1-year clinical outcomes in comparison with contemporary thicker strut second-generation DES.

This review aims to summarize the evidence and challenges of coronary artery calcium (CAC) scoring as a screening tool for coronary artery disease (CAD) in young adults. Several cohort studies have highlighted the value of CAC scoring in CAD risk assessment in young adults. The largest study to date is the Coronary Artery Risk Development in Young Adults (CARDIA) study. The study examined patients at 18–30 years of age and demonstrated that the presence of any degree of CAC was associated with a higher risk of coronary events compared to zero CAC, with an incremental increase in the risk of events with higher scores. However, it is important to note that 70% of patients screened had CAC = 0 at the age of 56. Despite the evidence that higher CAC score cutoff used in guidelines for predicting cardiovascular risk may be “falsely reassuring,” however, mass screening of young adults using CAC score may be challenging. The development of prediction tools and scoring systems to identify patients at higher risk of developing CAC based on known CAD risk factors may help reduce the number needed to screen to detect patients with positive CAC.

Objective To determine how two different types of iodinated contrast media (CM), low-osmolar ionic dimer ioxaglate (Hexabrix) and iso-osmolar non-ionic dimer iodixanol (Visipaque), affect multiple indices of hemostasis. Background In vitro models demonstrate differential effects of ionic and non-ionic CM on markers of hemostasis. Methods This blinded endpoint trial randomized 100 patients to ioxaglate or iodixanol. The primary endpoint was change in endogenous thrombin potential (ETP) following diagnostic angiography. Secondary endpoints included change in markers of fibrinolysis [tissue plasminogen activator (tPA) and plasminogen activator inhibitor 1 (PAI-1)] and platelet aggregation following diagnostic angiography and percutaneous coronary intervention (PCI) with bivalirudin. Data are presented as median [interquartile range]. Results ETP significantly decreased after diagnostic angiography in both ioxaglate (baseline 1810 nM*minute [1540-2089] to post-angiography 649 nM*minute [314-1347], p

Background COURAGE and BARI-2D have questioned the utility of routine revascularization for the prevention of cardiovascular events in patients with stable ischemic heart disease (SIHD). On the other end of the spectrum, a routine invasive strategy in patients with acute coronary syndrome (ACS) is superior to a conservative strategy. The impact of the above trials on the trend in percutaneous coronary intervention (PCI) volume for SIHD and ACS is not known. Methods Data from the 2001–2011 Nationwide Inpatient Sample for discharges with PCI were used. The trend in PCI volume over time was analyzed, especially in relation to the COURAGE (2007) and the BARI-2D (2009) trials. Age and gender adjusted PCI rates were calculated using direct standardization method. Results Among the 8,150,764 PCI procedures, there was a steady increase in PCI volumes until the publication of the COURAGE/BARI-2D trials after which the volume decreased. Compared to the peak volume of 909,331 in 2006, PCI volume declined by 38% to 562,036 in 2011 (P Conclusion The 11-year trend indicates a substantial impact of COURAGE/BARI-2D on SIHD PCI volumes with an unintended consequence of lower PCI volumes for ACS.

Patients with type 2 diabetes mellitus (T2DM) are at an increased risk of systemic atherosclerosis and advanced coronary artery disease (CAD). Herein, we review clinical trials comparing surgical to percutaneous revascularization in the context of the unique pathophysiology in this patient population, and seek to answer the question of optimal strategy of revascularization. Early studies showed a signal towards benefit of surgical revascularization over percutaneous revascularization in this group, but there was a paucity of randomized clinical trials (RCT) to directly support this finding. The Future Revascularization Evaluation in Patients with Diabetes Mellitus: Optimal Management of Multivessel Disease (FREEDOM), a large-scale international RCT, was then undertaken and established the benefit of coronary artery bypass grafting (CABG) over percutaneous coronary intervention (PCI) in terms of mortality, myocardial infarction and repeat revascularization; CABG was inferior to PCI with regards to stroke. The quality of life and cost effectiveness also demonstrated a long-term benefit for surgery. The decision as to choice of mode of revascularization in patients with T2DM and advanced CAD depends upon a multitude of factors, including the coronary anatomy, co-morbidities and the patient’s surgical risk. These factors influence the recommendation of the cardiovascular team, which should result in a balanced presentation of the short and long-term risks and benefits of either mode of revascularization to the patient and his/her family.

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 of13 g/dl for men and12 g/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%, p0.0001, major bleeding 8.8% vs 3.9%, p0.0001), and 1 year (composite ischemia 21.7% vs 15.3%, p0.0001). 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, p0.0001; nonanemic patients relative risk 2.16, 95% CI 1.76 to 2.65, p0.0001). In conclusion, in the ACUITY trial, baseline anemia was strongly associated with adverse early and late clinical events, especially in those who developed major bleeding.

Although lesion complexity is predictive of outcomes after balloon angioplasty, it is unclear whether complex lesions continue to portend a worse prognosis in patients with acute coronary syndrome (ACS) undergoing percutaneous coronary intervention (PCI) with contemporary interventional therapies. We sought to assess the impact of angiographic lesion complexity, defined by the modified American College of Cardiology/American Heart Association classification, on clinical outcomes after PCI in patients with ACS and to determine whether an interaction exists between lesion complexity and antithrombin regimen outcomes after PCI. Among the 3,661 patients who underwent PCI in the Acute Catheterization and Urgent Intervention Triage strategy study, patients with type C lesions (n = 1,654 [45%]) had higher 30-day rates of mortality (1.2% vs 0.6%, p = 0.049), myocardial infarction (9.2% vs 6.3%, p = 0.0006), and unplanned revascularization (4.3% vs 3.1%, p = 0.04) compared with those without type C lesions. In multivariate analysis, type C lesions were independently associated with myocardial infarction (odds ratio [95% confidence interval] = 1.37 [1.04 to 1.80], p = 0.02) and composite ischemia (odds ratio [95% confidence interval] = 1.49 [1.17 to 1.88], p = 0.001) at 30 days. Bivalirudin monotherapy compared with heparin plus a glycoprotein IIb/IIIa inhibitor reduced major bleeding complications with similar rates of composite ischemic events, regardless of the presence of type C lesions. There were no interactions between antithrombotic regimens and lesion complexity in terms of composite ischemia and major bleeding (p [interaction] = 0.91 and 0.80, respectively). In conclusion, patients with ACS with type C lesion characteristics undergoing PCI have an adverse short-term prognosis. Treatment with bivalirudin monotherapy reduces major hemorrhagic complications irrespective of lesion complexity with comparable suppression of adverse ischemic events as heparin plus glycoprotein IIb/IIIa inhibitor.

Background Drug eluting stents (DES) reduce the risk of restenosis but are associated with increase in the risk of very late stent thrombosis, especially when antiplatelet therapy is held. The trend in DES use across the US is not fully defined. Methods Data from the 2001–2011 Nationwide Inpatient Sample for patients undergoing PCI were used. The trend in DES use was analyzed overall and in subgroups at risk of restenosis (those with diabetes, chronic kidney disease or prior PCI), stent thrombosis (those with acute coronary syndrome) or bleeding (those with history of bleeding peptic ulcer or atrial fibrillation). Results Among the 8,150,763 PCI procedures performed, DES use peaked in 2005 at 89% in all patients including groups with a low risk of restenosis, high risk of stent thrombosis or bleeding. A steep drop to 66% was noted in 2007 followed by a progressive rise to 73% in 2011 (P Conclusions DES trends indicate rapid and broad initial use followed by a sharp decline in 2007 and a progressive rise in 2011. DES use in 2011 seemed based on risk category, but was lower in groups at risk for discriminant care.

Objectives: This study evaluated the impact of nonculprit vessel myocardial perfusion on outcomes of non–ST-segment elevation acute coronary syndromes (NSTE-ACS) patients.Background: ST-segment ele...

Reduced rates of cardiac catheterization, percutaneous coronary intervention (PCI), and coronary artery bypass graft (CABG) are an unintended consequence of public reporting of cardiogenic shock outcomes in New York.To evaluate whether the referral rates for cardiac catheterization, PCI, or CABG have improved in New York since cardiogenic shock was excluded from public reporting in 2008 and compare them with corresponding rates in Michigan, New Jersey, and California.Patients with cardiogenic shock complicating acute myocardial infarction from 2002 to 2011 were identified using the National Inpatient Sample. Propensity score matching was used to assemble a cohort of patients with cardiogenic shock with similar baseline characteristics in New York and Michigan.Percutaneous coronary intervention (primary outcome), invasive management (cardiac catheterization, PCI, or CABG), revascularization (PCI or CABG), and CABG were evaluated with reference to 3 calendar year periods: 2002-2005 (time 1: cardiogenic shock included in publicly reported outcomes), 2006-2007 (time 2: cardiogenic shock excluded on a trial basis), and 2008 and thereafter (time 3: cardiogenic shock excluded permanently) in New York and compared with Michigan.Among 2126 propensity score-matched patients representing 10 795 (weighted) patients with myocardial infarction complicated by cardiogenic shock in New York and Michigan, 905 (42.6%) were women and mean (SE) age was 69.5 (0.3) years. A significantly higher proportion of the patients underwent PCI (time 1 vs 2 vs 3: 31.1% vs 39.8% vs 40.7% [OR, 1.50; 95% CI, 1.12-2.01; P = .005 for time 3 vs 1]), invasive management (time 1 vs 2 vs 3: 59.7% vs 70.9% vs 73.8% [OR, 1.84; 95% CI, 1.37-2.47; P .001 for time 3 vs 1]), or revascularization (43.1% vs 55.9% vs 56.3% [OR, 1.66; 95% CI, 1.26-2.20; P .001 for time 3 vs 1]) after the exclusion of cardiogenic shock from public reporting in New York. However, during the same periods, a greater proportion of patients underwent PCI (time 1 vs 2 vs 3: 41.2% vs 52.6% vs 57.8% [OR, 1.93; 95% CI, 1.45-2.56; P .001 for time 3 vs 1]), invasive management (time 1 vs 2 vs 3: 64.4% vs 80.5% vs 78.6% [OR, 2.01; 95% CI, 1.47-2.74; P .001 for time 3 vs 1]), or revascularization (51.2% vs 65.8% vs 68.0% [OR, 2.00; 95% CI, 1.50-2.66; P .001 for times 3 vs 1]) in Michigan. Results were largely similar in several sensitivity analyses comparing New York with New Jersey or California.Although the rates of PCI, invasive management, and revascularization have increased substantially after the exclusion of cardiogenic shock from public reporting in New York, these rates remain consistently lower than those observed in other states without public reporting.

Left transradial approach (TRA) for coronary angiography is associated with lower radiation parameters than right TRA in an all-comers population. The aim of this study was to determine the effects of left versus right TRA on radiation parameters in patients with predictors of TRA failure. Patients with predictors of TRA failure (≥3 of 4 following criteria: age ≥70 years, female gender, height ≤64 inches, and hypertension) referred to TRA operators were randomized to either right (n = 50) or left (n = 50) TRA, whereas those referred to transfemoral approach (TFA) operators were enrolled in a prospective registry (n = 50). The primary end point was the radiation measure of dose-area product (DAP). In an intention-to-treat analysis, DAP (34.1 Gy·cm(2) [24.9 to 45.6] vs 41.9 Gy·cm(2) [27.3 to 58.0], p = 0.08), fluoroscopy time (3.7 minutes [2.4 to 6.3] vs 5.6 minutes [3.1 to 8.7], p = 0.07), and operator radiation exposure (516 μR [275 to 967] vs 730 μR [503 to 1,165], p = 0.06) were not significantly different between left and right TRA, but total dose (411 mGy [310 to 592] vs 537 mGy [368 to 780], p = 0.03) was significantly lower with left versus right TRA. Radiation parameters were lowest in the TFA cohort (DAP 24.5 Gy·cm(2) [15.7 to 33.2], p0.001; fluoroscopy time 2.3 minutes [1.5 to 3.7], p0.001; operator radiation exposure 387 μR [264 to 557]; total dose 345 mGy [250 to 468], p = 0.001). Results were similar after adjustment for differences in baseline characteristics. In conclusion, median measurements of radiation were overall not significantly different between left versus right TRA in this select population of patients with predictors of TRA failure. All measurements of radiation were lowest in the TFA group.

Women are frequently reported to have increased morbidity after presentation with acute coronary syndromes and myocardial infarction; however, whether a greater thrombotic tendency contributes to gender differences in clinical outcomes of urgent percutaneous coronary intervention is unknown. Intraprocedural Thrombotic Events (IPTEs) are defined as new or increasing thrombus, abrupt vessel closure, no reflow or slow reflow, or distal embolization at any time during percutaneous coronary intervention. IPTEs were evaluated in this pooled analysis of 6,591 patients with stent implantation and blinded quantitative coronary angiography (QCA) analysis, from the ACUITY and HORIZONS-AMI trials. We compared major adverse cardiac events (MACE) at in-hospital, 30-day, and 1-year follow-up and major bleeding at 30 days according to gender and the presence or absence of IPTE. IPTE was identified in 507 patients (7.7%), with 119 of 1,744 (6.8%) occurring in women and 388 of 4,847 (8.0%) in men (p = 0.12). IPTE, but not gender, was independently associated with MACE at in-hospital and 30-day follow-up. At 1-year follow-up, the adjusted hazard of MACE was higher in women and in patients with IPTE; however, the risk of MACE associated with IPTE was similar among women and men. There was no significant interaction between IPTE and gender for 1-year MACE or 30-day bleeding. IPTE predicted major bleeding only in women. In conclusion, in acute coronary syndromes, women have increased risk of adverse outcome at 1 year. IPTEs are common, occur at similar frequency, and are associated with similar degree of increased MACE in both genders at short- and long-term follow-up. Higher thrombotic propensity does not offer a mechanistic explanation for the worse outcomes noted in women.

Background— The Bypass Angioplasty Revascularization Investigation 2 Diabetes (BARI 2D) trial assigned patients with type 2 diabetes mellitus to prompt coronary revascularization plus intensive medical therapy versus intensive medical therapy alone and reported no significant difference in mortality. Among patients selected for coronary artery bypass graft surgery, prompt coronary revascularization was associated with a significant reduction in death/myocardial infarction/stroke compared with intensive medical therapy. We hypothesized that clinical and angiographic risk stratification would affect the effectiveness of the treatments overall and within revascularization strata. Methods and Results— An angiographic risk score was developed from variables assessed at randomization; independent prognostic factors were myocardial jeopardy index, total number of coronary lesions, prior coronary revascularization, and left ventricular ejection fraction. The Framingham Risk Score for patients with coronary disease was used to summarize clinical risk. Cardiovascular event rates were compared by assigned treatment within high-risk and low-risk subgroups. Overall, no outcome differences between the intensive medical therapy and prompt coronary revascularization groups were seen in any risk stratum. The 5-year risk of death/myocardial infarction/stroke was 36.8% for intensive medical therapy compared with 24.8% for prompt coronary revascularization among the 381 coronary artery bypass graft surgery–selected patients in the highest angiographic risk tertile ( P =0.005); this treatment effect was amplified in patients with both high angiographic and high Framingham risk (47.3% intensive medical therapy versus 27.1% prompt coronary revascularization; P =0.010; hazard ratio=2.10; P =0.009). Treatment group differences were not significant in other clinical-angiographic risk groups within the coronary artery bypass graft surgery stratum, or in any subgroups within the percutaneous coronary intervention stratum. Conclusion— Among patients with diabetes mellitus and stable ischemic heart disease, a strategy of prompt coronary artery bypass graft surgery significantly reduces the rate of death/myocardial infarction MI/stroke in those with extensive coronary artery disease or impaired left ventricular function. Clinical Trial Registration— URL: http://www.clinicaltrials.gov . Unique identifier: NCT00006305.

Background— Drug-eluting stents (DES) have been in clinical use for nearly a decade; however, the relative short- and long-term efficacy and safety of DES compared with bare-metal stents (BMS) and among the DES types are less well defined. Methods and Results— PubMed, Embase, and Cochrane Central Register of Controlled Trials (CENTRAL) were searched for randomized clinical trials, until March 2012, that compared any of the Food and Drug Administration–approved durable stent and polymer DES (sirolimus-eluting stent [SES], paclitaxel-eluting stent [PES], everolimus-eluting stent [EES], zotarolimus-eluting stent [ZES], and ZES-Resolute [ZES-R]) with each other or against BMS for de novo coronary lesions, enrolling at least 100 patients and with follow-up of at least 6 months. Short-term (≤1 year) and long-term efficacy (target-vessel revascularization, target-lesion revascularization) and safety (death, myocardial infarction, stent thrombosis) outcomes were evaluated and trial-level data pooled by both mixed-treatment comparison and direct comparison analyses. From 76 randomized clinical trials with 117 762 patient-years of follow-up, compared with BMS, each DES reduced long-term target-vessel revascularization (39%–61%), but the magnitude varied by DES type (EES∼SES∼ZES-R>PES∼ZES>BMS), with a >42% probability that EES had the lowest target-vessel revascularization rate. There was no increase in the risk of any long-term safety outcomes, including stent thrombosis, with any DES (versus BMS). In addition, there was reduction in myocardial infarction (all DES except PES versus BMS) and stent thrombosis (with EES versus BMS: Rate ratio, 0.51; 95% credibility interval, 0.35–0.73). The safest DES appeared to be EES (>86% probability), with reduction in myocardial infarction and stent thrombosis compared with BMS. Short-term outcomes were similar to long-term outcomes, with SES, ZES-R, and everolimus-eluting stent being the most efficacious and EES being the safest stent. Conclusions— DES are highly efficacious at reducing the risk of target-vessel revascularization without an increase in any safety outcomes, including stent thrombosis. However, among the DES types, there were considerable differences, such that EES, SES, and ZES-R were the most efficacious and EES was the safest stent.

Background— Patients with diabetes have more extensive coronary disease than those without diabetes, resulting in more challenging percutaneous coronary intervention or surgical (coronary artery bypass graft) revascularization and more residual jeopardized myocardium. The Bypass Angioplasty Revascularization Investigation 2 Diabetes (BARI 2D) trial provided an opportunity to examine the long-term clinical impact of completeness of revascularization in patients with diabetes. Methods and Results— This is a post hoc, nonrandomized analysis of the completeness of revascularization in 751 patients who were randomly assigned to early revascularization, of whom 264 underwent coronary artery bypass graft surgery and 487 underwent percutaneous coronary intervention. The completeness of revascularization was determined by the residual postprocedure myocardial jeopardy index (RMJI). RMJI is a ratio of the number of myocardial territories supplied by a significantly diseased epicardial coronary artery or branch that was not successfully revascularized, divided by the total number of myocardial territories. Mean follow-up for mortality was 5.3 years. Complete revascularization (RMJI=0) was achieved in 37.9% of patients, mildly incomplete revascularization (RMJI >0≤33) in 46.6%, and moderately to severely incomplete revascularization (RMJI >33) in 15.4%. Adjusted event-free survival was higher in patients with more complete revascularization (hazard ratio, 1.14; P =0.0018). Conclusions— Patients with type 2 diabetes mellitus and less complete revascularization had more long-term cardiovascular events. Clinical Trial Registration— URL: http://www.clinicaltrials.gov . Unique identifier: NCT00006305.

Objectives 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). Background 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. Methods 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. Results 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 Conclusions 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.

Objectives 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. Background Bleeding complications after PCI have been independently associated with early and late mortality. Methods 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. Results 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 Conclusions 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.

Background— Contemporary adjunctive pharmacology and revascularization strategies have improved the prognosis of patients with acute coronary syndromes (ACSs). We sought to identify the clinical and angiographic predictors of cardiac ischemic events in patients with ACSs treated with an early invasive strategy. Methods and Results— Multivariable logistic regression was used to analyze the relation between baseline characteristics and 30-day and 1-year composite ischemia (death, myocardial infarction, or unplanned revascularization) among the 6921 ACS patients included in the prespecified angiographic substudy of the Acute Catheterization and Urgent Intervention Triage strategY (ACUITY) trial. Of the 6921 patients, 3826 (55.3%) were treated with percutaneous coronary intervention, 755 (10.9%) with coronary artery bypass grafting, and 2340 (33.8%) with medical therapy. Composite ischemia occurred in 595 (8.6%) patients at 30 days and in 1153 (17.4%) at 1 year. Renal insufficiency, biomarker elevation, ST-segment deviation, nonuse of aspirin or thienopyridine, insulin-treated diabetes, older age, baseline lower hemoglobin value, history of percutaneous coronary intervention, and current smoking were independently associated with 30-day or 1-year ischemic events. Angiographic characteristics predicting ischemic events included number of diseased vessels, moderate/severe calcification, worst percent diameter stenosis, jeopardy score, lower left ventricular ejection fraction, lesion eccentricity, and thrombus. With use of receiver operating characteristic methodology, the c statistic improved for the predictive model by adding angiographic to clinical parameters for the 30-day composite ischemia (from 0.62 to 0.68) and myocardial infarction (from 0.64 to 0.71) and 1-year composite ischemia (from 0.61 to 0.65) and myocardial infarction (from 0.63 to 0.69) end points. Conclusions— Among ACS patients managed with an early invasive strategy, baseline angiographic markers of disease burden, calcification, lesion severity, lower left ventricular ejection fraction, and morphological characteristics provided important added independent predictive value for 30-day and 1-year ischemic outcomes, beyond the well-recognized clinical risk factors. These findings emphasize the prognostic importance of the diagnostic angiogram in the risk stratification of patients presenting with ACSs. Clinical Trial Registration— URL: http://clinicaltrials.gov . Unique identifier: NCT00093158.

Background A substantial minority of patients with acute coronary syndromes (ACS) do not have a diameter stenosis of any major epicardial coronary artery on angiography (“no obstruction at angiography”) of ≥ 50%. We examined the frequency of this finding and its relationship to race and sex. Hypothesis Among patients with myocardial infarction, younger age, female sex and non-white race are associated with the absence of obstructive coronary artery disease at angiography. Methods We reviewed the results of all angiograms performed from May 19, 2006 to September 29, 2006 at 1 private (n = 793) and 1 public (n = 578) urban academic medical center. Charts were reviewed for indication and results of angiography, and for demographics. Results The cohort included 518 patients with ACS. There was no obstruction at angiography in 106 patients (21%), including 48 (18%) of 258 patients with myocardial infarction. Women were more likely to have no obstruction at angiography than men, both in the overall cohort (55/170 women [32%] vs 51/348 men [15%], P < 0.001) and in the subset with MI (29/90 women [32%] vs 19/168 men [11%], P < 0.001). Black patients were more likely to have no obstruction at angiography relative to any other subgroup (24/66 [36%] vs 41/229 [18%] Whites, 31/150 [21%] Hispanics, and 5/58 [9%] Asians, P = 0.001). Among women, Black patients more frequently had no obstruction at angiography compared with other ethnic groups (16/27 [59%] vs 17/59 [29%] Whites, 17/60 [28%] Hispanics, and 3/19 [6%] Asians, P = 0.001). Conclusions A high proportion of a multiethnic sample of patients with ACS were found to have no stenosis ≥ 50% in diameter at coronary angiography. This was particularly common among women and Black patients. Copyright © 2010 Wiley Periodicals, Inc. This work was supported by the Doris Duke Charitable Foundation. Dr Reynolds is a recipient of the Doris Duke Charitable Foundation Clinical Scientist Development Award. The authors have no other funding, financial relationships, or conflicts of interest to disclose.

Abciximab and eptifibatide have been shown to reduce ischemic complications compared with heparin alone in patients with acute coronary syndromes who undergo percutaneous coronary intervention. Whether 1 agent is safer and/or more effective has not been prospectively examined. The aim of this study was to assess the outcomes related to downstream glycoprotein IIb/IIIa inhibitor treatment selection during percutaneous coronary intervention in 2,211 patients with moderate and high-risk acute coronary syndromes in the prospective multicenter Acute Catheterization and Urgent Intervention Triage Strategy (ACUITY) trial. The protocol permitted operator selection of abciximab (n = 835) or eptifibatide (n = 1,376) for routine use in the trial. Multivariate and propensity-based adjustments were used to assess the independent association of glycoprotein IIb/IIIa inhibitor treatment selection with prespecified study end points. Compared to patients receiving eptifibatide, those administered abciximab were older, more likely to be enrolled outside of North America, more frequently had biomarker elevations and ST-segment deviation, but had fewer baseline cardiac risk factors and previous revascularization procedures. After multivariate propensity-based adjustment, abciximab was independently associated with significantly fewer net clinical adverse events (odds ratio 0.61, 95% confidence interval 0.42 to 0.90, p = 0.01), mediated by composite ischemia (odds ratio 0.61, 95% confidence interval 0.38 to 0.98, p = 0.04) and major bleeding (odds ratio 0.58, 95% confidence interval 0.34 to 1.00, p = 0.051). In conclusion, in this prespecified but nonrandomized comparison in patients with acute coronary syndromes who underwent percutaneous coronary intervention with catheterization laboratory initiation of glycoprotein IIb/IIIa inhibitors, the use of abciximab rather than eptifibatide was associated with improved clinical outcomes at 30 days. These findings should be viewed as exploratory in light of the nonrandomized and heterogeneous nature of the comparator groups and significant potential for residual confounding.

Background— Outcomes of patients presenting with acute coronary syndromes are improved with an early invasive approach; however, approximately one third of these patients are treated medically after angiographic screening. We sought to assess the predictors of adverse cardiac events in patients with acute coronary syndrome assigned to medical management. Methods and Results— This substudy of the Acute Catheterization and Urgent Intervention Triage Strategy (ACUITY) trial included 4491 acute coronary syndrome patients treated medically after angiographic triage. Rates of bleeding and composite ischemia (death, myocardial infarction, revascularization) were compared among the 3 antithrombotic treatment arms. Composite ischemia occurred in 399 patients (9.5%) at 1 year. Treatment with bivalirudin glycoprotein IIb/IIIa inhibitors significantly reduced major bleeding at 30 days (2.5% bivalirudin monotherapy; P =0.005, 2.0% bivalirudin plus glycoprotein IIb/IIIa inhibitors; P =0.0002 versus 4.4% heparin with glycoprotein IIb/IIIa inhibitors). Composite ischemic events at 1 year were not significantly different in the 3 groups (bivalirudin monotherapy, 9.6%; bivalirudin plus glycoprotein IIb/IIIa inhibitors, 9.7%; heparin plus glycoprotein IIb/IIIa inhibitors, 9.1%). Independent predictors of composite ischemia were mostly angiographic factors at 30 days, including jeopardy score and coronary ectasia, and at 1 year, including previous percutaneous coronary intervention, jeopardy score, coronary ectasia, and increasing number of diseased vessels. Conclusions— Among the ACUITY acute coronary syndrome patients treated medically after angiographic triage, bivalirudin therapy significantly reduced bleeding complications compared with heparin without any negative impact on ischemic outcomes at 1 year. The most powerful predictors of ischemic outcomes were angiographic rather than traditional clinical parameters, supporting the early use of angiographic screening in the moderate- and high-risk but medically treated acute coronary syndrome population. Clinical Trial Registration— URL: http://www.clinicaltrials.gov. Unique identifier: NCT00093158.

Background— The Acute Catheterization and Urgent Intervention Triage Strategy (ACUITY) trial demonstrated that bivalirudin monotherapy significantly reduces major bleeding compared with heparin (unfractionated or enoxaparin) or bivalirudin plus a glycoprotein IIb/IIIa inhibitor in acute coronary syndromes. Whether vascular closure devices (VCD) impact these results is unknown. Therefore, this study sought to determine whether VCD impact major access site bleeding (ASB) in patients with acute coronary syndromes undergoing early invasive management by the femoral approach. Methods and Results— Major ASB in ACUITY was defined as ASB requiring interventional or surgical correction, hematoma ≥5 cm at the access site, retroperitoneal bleeding, or hemoglobin drop ≥3 g/dL with ecchymosis or hematoma 30 minutes) at the access site. Stepwise logistical regression was performed to identify the independent determinants of ASB. Of 11 621 patients undergoing angiography with or without percutaneous coronary intervention by the femoral approach, 4307 (37.1%) received a VCD and 7314 (62.9%) did not. Rates of major ASB were lower with VCD compared with no VCD (2.5% versus 3.3%, relative risk, 0.76; 95% CI, 0.61 to 0.94; P =0.01) and were lowest in patients treated with bivalirudin monotherapy and a VCD (0.7%). Stepwise logistic regression revealed that a VCD (odds ratio, 0.78; 95% CI, 0.61 to 0.99; P =0.04) and bivalirudin monotherapy (odds ratio, 0.35; 95% CI, 0.25 to 0.49; P Conclusion— In patients with acute coronary syndromes undergoing an early invasive management strategy by the femoral approach, the use of a VCD, bivalirudin monotherapy, or both minimizes rates of major ASB. Clinical Trial Registration— URL: http://www.clinicaltrials.gov. Unique Identifier: NCT00093158.

Objectives We assessed the incidence, predictors, and outcomes of gastrointestinal bleeding (GIB) in patients with acute coronary syndromes (ACS). Background GIB is a potential hemorrhagic complication in patients with ACS treated with antithrombotic and/or antiplatelet medications. The clinical outcomes associated with GIB in this setting have not been systematically studied. Methods In the ACUITY (Acute Catheterization and Urgent Intervention Triage Strategy) trial, 13,819 patients with moderate- and high-risk ACS, enrolled at 450 centers in 17 countries between August 2003 and December 2005, were randomized to the open-label use of 1 of 3 antithrombin regimens (heparin plus a glycoprotein IIb/IIIa inhibitor, bivalirudin plus a glycoprotein IIb/IIIa inhibitor, or bivalirudin monotherapy). Results GIB within 30 days occurred in 178 patients (1.3%). Older age, baseline anemia, longer duration of study drug administration before angiogram, smoking, ST-segment deviation ≥1 mm, and diabetes were identified as independent predictors of GIB. On multivariable analysis, GIB was strongly associated with 30-day all-cause mortality (hazard ratio [HR]: 4.87 [interquartile range (IQR) 2.61 to 9.08], p Conclusions GIB is a serious condition in the scenario of ACS and is independently associated with mortality and ischemic complications.

Objectives In this substudy of the ACUITY (Acute Catheterization and Urgent Intervention Triage strategY) trial, we investigated the relationship between chronic kidney disease (CKD) and clinical outcomes, and compared the safety and efficacy of bivalirudin monotherapy versus heparin plus a glycoprotein IIb/IIIa inhibitor (GPI). Background CKD is an important predictor of prognosis in the general population. The outcomes of patients with CKD and acute coronary syndromes (ACS) have not been well studied. Methods In the ACUITY study, 13,819 patients with moderate- and high-risk ACS undergoing an early, invasive strategy were randomly assigned to 1 of 3 antithrombin regimens: a heparin plus a GPI, bivalirudin plus a GPI, or bivalirudin monotherapy. CKD (creatinine clearance Results Patients with CKD had worse 30-day and 1-year clinical outcomes than those with normal renal function. There were no significant differences between bivalirudin monotherapy and heparin plus a GPI in rates of 30-day composite ischemia (11.1% vs. 9.4%, p = 0.27) and net clinical adverse outcomes (16.1% vs. 16.9%, p = 0.65). There was remarkably less major bleeding (6.2% vs. 9.8%, p = 0.008) at 30 days, but no significant difference in 1-year composite ischemia (22.0% vs. 18.9%, p = 0.10) or mortality (7.1% vs. 7.3%, p = 0.96). Conclusions In patients with ACS, CKD is associated with higher 30-day and 1-year adverse event rates. Compared with heparin plus a GPI, the use of bivalirudin monotherapy in patients with CKD results in nonstatistically different ischemic outcomes, but significantly less 30-day major bleeding.

ObjectivesWe evaluated demographic, clinical, and angiographic factors influencing the selection of coronary artery bypass graft (CABG) surgery versus percutaneous coronary intervention (PCI) in diabetic patients with multivessel coronary artery disease (CAD) in the BARI 2D (Bypass Angioplasty Revascularization Investigation in Type 2 Diabetes) trial.BackgroundFactors guiding selection of mode of revascularization for patients with diabetes mellitus and multivessel CAD are not clearly defined.MethodsIn the BARI 2D trial, the selected revascularization strategy, CABG or PCI, was based on physician discretion, declared independent of randomization to either immediate or deferred revascularization if clinically warranted. We analyzed factors favoring selection of CABG versus PCI in 1,593 diabetic patients with multivessel CAD enrolled between 2001 and 2005.ResultsSelection of CABG over PCI was declared in 44% of patients and was driven by angiographic factors including triple vessel disease (odds ratio [OR]: 4.43), left anterior descending stenosis ≥70% (OR: 2.86), proximal left anterior descending stenosis ≥50% (OR: 1.78), total occlusion (OR: 2.35), and multiple class C lesions (OR: 2.06) (all p < 0.005). Nonangiographic predictors of CABG included age ≥65 years (OR: 1.43, p = 0.011) and non-U.S. region (OR: 2.89, p = 0.017). Absence of prior PCI (OR: 0.45, p < 0.001) and the availability of drug-eluting stents conferred a lower probability of choosing CABG (OR: 0.60, p = 0.003).ConclusionsThe majority of diabetic patients with multivessel disease were selected for PCI rather than CABG. Preference for CABG over PCI was largely based on angiographic features related to the extent, location, and nature of CAD, as well as geographic, demographic, and clinical factors. (Bypass Angioplasty Revascularization Investigation in Type 2 Diabetes [BARI 2D]; NCT00006305)

Objectives This study sought to evaluate the impact of upstream clopidogrel in patients with non–ST-segment elevation acute coronary syndromes (NSTE-ACS) requiring coronary artery bypass grafting (CABG) from the ACUITY (Acute Catheterization and Urgent Intervention Triage strategY) trial. Background Despite benefits of clopidogrel in patients with NSTE-ACS undergoing percutaneous coronary intervention, this agent is often not administered upstream (before angiography) as recommended by the American College of Cardiology/American Heart Association guidelines because of potential bleeding in the minority of patients who require CABG. Methods The ACUITY trial enrolled 13,819 patients with NSTE-ACS undergoing early invasive management. The timing of clopidogrel initiation was per investigator discretion. A 5-day washout period before CABG was recommended for patients having received clopidogrel. Results Of 13,819 patients enrolled, 1,539 (11.1%) underwent CABG before discharge. Clopidogrel-exposed patients had a longer median duration of hospitalization (12.0 days vs. 8.9 days, p Conclusions Clopidogrel administration before catheterization in patients with NSTE-ACS requiring CABG is associated with significantly fewer 30-day adverse ischemic events without significantly increasing major bleeding, compared to withholding clopidogrel until after angiography. These findings support the American College of Cardiology/American Heart Association guidelines for upstream clopidogrel administration in all NSTE-ACS patients, including those who subsequently undergo CABG. (Comparison of Angiomax Versus Heparin in Acute Coronary Syndromes [ACS]; NCT00093158 ).

Aims To evaluate the associations of myocardial infarction (MI) and major bleeding with 1-year mortality. Both MI and major bleeding predict 1-year mortality in patients presenting with acute coronary syndrome (ACS). However, the risk of each of these events on the magnitude and timing of mortality has not been well studied. Methods and Results A multivariable Cox regression model was developed relating 13 independent baseline predictors to 1-year mortality for 13 819 patients with moderate and high-risk ACS enrolled in the Acute Catheterization and Urgent Intervention Triage strategy trial. After adjustment for baseline predictors, Cox models with major bleeding and recurrent MI as time-updated covariates estimated the effect of these events on mortality hazard over time. Within 30 days of randomization, 705 patients (5.1%) had an MI, 645 (4.7%) had a major bleed; 524 (3.8%) died within a year. The occurrence of an MI was associated with a hazard ratio of 3.1 compared with patients not yet having an MI, after adjustment for baseline predictors. However, MI within 30 days markedly increased the mortality risk for the first 2 days after the event (adjusted hazard ratio of 17.6), but this risk declined rapidly post-infarct (hazard ratio of 1.4 beyond 1 month after the MI event). In contrast, major bleeding had a prolonged association with mortality risk (hazard ratio of 3.5) which remained fairly steady over time throughout 1 year. Conclusion After accounting for baseline predictors of mortality, major bleeds and MI have similar overall strength of association with mortality in the first year after ACS. MI is correlated with a dramatic increase in short-term risk, whereas major bleeding correlates with a more prolonged mortality risk.

Objectives This study sought to evaluate the impact of age on outcomes in patients with moderate- and high-risk non–ST-segment elevation acute coronary syndrome (NSTE-ACS) enrolled in the ACUITY (Acute Catheterization and Urgent Intervention Triage Strategy) trial. Background Aging-associated changes in physiology and metabolism may alter the risk and benefit of therapeutic strategies from that observed in younger people. Methods We performed a pre-specified analysis of 30-day and 1-year outcomes in 4 age groups, overall and among those undergoing percutaneous coronary intervention (PCI). Results Of 13,819 patients in the ACUITY trial, 3,655 (26.4%) were Conclusions Ischemic and bleeding complications after NSTE-ACS increase with age. Although ischemic event rates are not statistically different with either bivalirudin alone or a heparin plus glycoprotein IIb/IIIa inhibitor, bleeding complications are significantly less frequent with bivalirudin alone. Because of the substantial risk of bleeding in patients age ≥75 years, the number needed to treat to avoid 1 major bleeding event using bivalirudin alone was the lowest in the elderly group, especially among those undergoing PCI. (Comparison of Angiomax Versus Heparin in Acute Coronary Syndromes [ACS]; NCT00093158 )

Objectives This study sought to determine if the efficacy of bivalirudin alone versus heparin plus a glycoprotein (GP) IIb/IIIa inhibitor is dependent upon the duration of clopidogrel pre-treatment in patients undergoing percutaneous coronary intervention (PCI) in the ACUITY (Acute Catheterization and Urgent Intervention Triage strategY) trial. Background The administration of a clopidogrel loading dose several hours before PCI reduces the risk of periprocedural thrombotic events. Methods Patients with an acute coronary syndrome were randomized to heparin plus a GP IIb/IIIa inhibitor (control), bivalirudin plus a GP IIb/IIIa inhibitor, or bivalirudin alone. Dose and timing of clopidogrel were left to the investigator9s discretion. Results Of 13,819 patients randomized, 7,789 underwent PCI. When clopidogrel was initiated at any time before angiography or within 30 min after PCI, randomization to bivalirudin alone (n = 2,284) or control (n = 2,189) was associated with similar ischemic outcomes (8.2% vs. 8.3%, risk ratio: 0.98, 95% confidence interval: 0.81 to 1.20). Those patients who received clopidogrel g30 min after PCI or not at all experienced an increase in ischemic events when randomized to bivalirudin alone (n = 290) versus control (n = 317) (14.1% vs. 8.5%, risk ratio: 1.66, 95% confidence interval: 1.05 to 2.63). Major bleeding was significantly less frequent in patients treated with bivalirudin alone. Conclusions This post-hoc analysis suggests that in acute coronary syndrome patients, as long as clopidogrel is administered before or within 30 min of PCI treatment with bivalirudin alone is similarly effective to heparin plus a GP IIb/IIIa inhibitor in suppressing 30-day ischemic events with significantly less bleeding. If it is anticipated that clopidogrel will be given late or not at all after PCI, bivalirudin alone may be associated with worse ischemic outcomes. (Comparison of Angiomax Versus Heparin in Acute Coronary Syndromes; NCT00093158)

Background Advances in coronary angioplasty and adjunct pharmacology have improved patient outcomes after primary percutaneous coronary intervention (PCI) in acute myocardial infarction (AMI). However, several areas for improvement remain. Hemorrhagic complications, which are common in patients receiving intense anticoagulant and antiplatelet agents during primary PCI to suppress ischemia, have been strongly associated with early and late mortality. Moreover, restenosis after bare-metal stents (BMSs) frequently results in symptom recurrence and the need for repeat rehospitalization and revascularization procedures. Newer pharmacologic agents and drug-eluting stents may address both of these issues. Study Design In the HORIZONS-AMI trial, 3,602 patients with AMI undergoing primary PCI were prospectively randomized to unfractionated heparin plus routine use of glycoprotein (GP) IIb/IIIa inhibitors versus the direct thrombin inhibitor bivalirudin plus provisional use of GP IIb/IIIa inhibitors reserved for predefined thrombotic complications. In a second randomization, 3,011 eligible patients were randomly assigned to either a polymer-based paclitaxel-eluting stent or to an otherwise identical BMS. The study was powered for the assessment of sequential safety and efficacy end points for each specific randomization, with clinical end points assessed at 30 days, 1 year, and then annually for 5 years. Summary The ongoing HORIZONS-AMI trial will determine whether bivalirudin monotherapy reduces bleeding complications and improves overall event-free survival compared with unfractionated heparin plus the routine use of GP IIb/IIIa inhibitors in patients undergoing primary PCI for AMI. Furthermore, this study will determine whether paclitaxel-eluting stents safely reduce rates of ischemic target lesion revascularization compared with BMSs in the setting of primary PCI.

The influence of metabolic syndrome (MS) on long-term mortality and morbidity in multi-vessel coronary artery disease (MV-CAD) is unclear. We studied the impact of MS on long-term outcomes in non-diabetic patients (NDM) with MV-CAD undergoing coronary revascularization in the Bypass Angioplasty Revascularization Investigation (BARI) trial and registry.BARI trial and registry patients were separated into those with diabetes (DM) and those without. NDM fulfilling the NCEP definition of MS were identified. Ten year follow-up data were obtained on mortality, MI and development of diabetes. The data were analyzed using Cox proportional hazard modeling.In the BARI trial and registry 2962 NDM were identified. Of those, 510 patients had 3 or more components of the BARI-modified NCEP definition for MS, while 445 patients had 2 components of the definition and were classified as the "mixed group". Compared to patients without MS, both MS group (RR=3.2, p0.0001) and the mixed group (RR=1.9, p=0.02) had a higher incidence of DM over the 10-year follow-up. Type 2 DM was found to be highly associated with 10-year mortality (RR=1.65, p0.0001). However, there was no statistically significant difference in the rate of death or MI at 5 and 10 years between NDM with or without MS. In multivariate analysis, the presence of MS was not associated with 10-year mortality in the BARI population (RR=0.93, p=0.62).In this BARI follow-up study, we have affirmed the role of MS in predicting the development of diabetes in NDM at baseline. The 10-year risk of mortality and MI was not greater in NDM with MS who had MV-CAD and underwent revascularization, compared to patients without MS. Further studies to evaluate MS patients with MV-CAD undergoing coronary revascularization are warranted.

Objectives The aim of this study was to compare outcomes in patients receiving consistent unfractionated heparin (UFH)/enoxaparin (ENOX) therapy and in those switched at randomization to bivalirudin monotherapy. Background Crossover between UFH and ENOX has been associated with increased adverse outcomes in patients with acute coronary syndromes. The ACUITY (Acute Catheterization and Urgent Intervention Triage strategY) trial demonstrated superior net clinical outcomes with similar rates of ischemia and significantly less major bleeding with bivalirudin monotherapy compared with UFH/ENOX plus a glycoprotein (GP) IIb/IIIa inhibitor. It is unknown if these results would be preserved in patients switched from UFH/ENOX to bivalirudin monotherapy. Methods We compared composite ischemia, major bleeding, and net clinical outcomes at 30 days in patients receiving consistent UFH/ENOX therapy and in those switched at randomization from pre-treatment with UFH/ENOX to bivalirudin monotherapy. We also compared outcomes in patients naive to antithrombin therapy who were randomized to UFH/ENOX or bivalirudin monotherapy. Results Two thousand one hundred thirty-seven patients received consistent UFH/ENOX (UFH n = 1,294, ENOX n = 843), and 2,078 patients pre-treated with UFH/ENOX were switched to bivalirudin. Patients switching to bivalirudin had similar rates of ischemia (6.9% vs. 7.4%, p = 0.52), less major bleeding (2.8% vs. 5.8%, p Conclusions Switching from UFH/ENOX to bivalirudin monotherapy results in comparable ischemic outcomes and an approximately 50% reduction in major bleeding compared with consistent UFH/ENOX plus a GP IIb/IIIa inhibitor. Patients naive to antithrombin therapy administered bivalirudin monotherapy had a significant reduction in bleeding and similar rates of ischemia compared with naive patients initiated with UFH or ENOX plus a GP IIb/IIIa inhibitor.

Objectives We sought to evaluate clinical outcomes of patients with diabetes mellitus in the ACUITY (Acute Catheterization and Urgent Intervention Triage Strategy) trial, overall and by treatment arm. Background In the ACUITY trial, 13,819 patients with moderate- or high-risk acute coronary syndromes (ACS) were randomized to heparin (unfractionated or enoxaparin) plus glycoprotein IIb/IIIa inhibition (GPI), bivalirudin plus GPI, or bivalirudin monotherapy. Compared with heparin plus GPI, bivalirudin monotherapy resulted in similar protection from ischemic events with less major bleeding. Whether these results apply to patients with diabetes is unknown. Methods We evaluated the impact of diabetes on 30-day net adverse clinical outcomes (composite ischemia [death, myocardial infarction, or unplanned ischemic revascularization] or major bleeding), overall and by antithrombotic strategy. Results Diabetes was present in 3,852 randomized patients (27.9%). Compared with nondiabetic patients, diabetic patients had higher 30-day rates of net adverse clinical outcomes (12.9% vs. 10.6%; p Conclusions Diabetic patients with ACS managed invasively have higher rates of composite ischemia and major bleeding. Compared with treatment with heparin plus GPI, bivalirudin monotherapy provides similar protection from ischemic events with less major bleeding, resulting in a significant reduction in net adverse clinical outcomes.

Patients undergoing percutaneous coronary intervention (PCI) have a significant risk of hemorrhagic complications. Predictors of major hemorrhage and its relation to mortality in PCI are not well defined. Baseline and periprocedural predictors of major hemorrhage and its impact on mortality in patients undergoing elective or urgent PCI randomly assigned to heparin plus planned glycoprotein IIb/IIIa inhibitor (GPI) versus bivalirudin plus provisional GPIs in the REPLACE-2 Trial were determined. Of 6,001 patients, 3.2% experienced a major hemorrhage. Independent baseline predictors of major hemorrhage included advanced age, female gender, impaired creatinine clearance, and anemia. Independent periprocedural predictors of major hemorrhage included treatment with heparin plus GPI, increased procedural duration, provisional use of GPI, increased time to sheath removal, length of intensive care unit stay, and use of an intra-aortic balloon pump (all p

The relation across anemia, hemorrhagic complications, and mortality associated with percutaneous coronary intervention (PCI) is unclear. We reviewed the Randomized Evaluation in PCI Linking Angiomax to Reduced Clinical Events (REPLACE)-2 Trial, which compared bivalirudin plus provisional glycoprotein IIb/IIIa blockade with heparin plus planned glycoprotein IIb/IIIa blockade in patients undergoing urgent or elective PCI. Of the 6,010 patients randomized in REPLACE-2, 1,371 (23%) were anemic. Major bleeding was more common in anemic than in nonanemic patients (4.9% vs 2.8%, p = 0.0001). In anemic patients, treatment with bivalirudin (n = 678) resulted in a lower risk of major bleeding versus heparin plus glycoprotein IIb/IIIa blockade (n = 693, 3.5% vs 6.2%, p = 0.0221). Mortality was higher in anemic patients than in nonanemic patients at 30 days (0.9% vs 0.2%, p

Objectives The purpose of this study was to determine the predictors of major bleeding and the impact of major bleeding on outcomes, including mortality, in acute coronary syndromes (ACS). Background Whether major bleeding independently predicts mortality in patients with ACS undergoing an early invasive strategy is undefined. Methods Patients (n = 13,819) with moderate- and high-risk ACS were randomized to heparin (unfractionated or enoxaparin) plus glycoprotein IIb/IIIa inhibition (GPI), bivalirudin plus GPI, or bivalirudin monotherapy (plus provisional GPI). Logistic regression was used to determine predictors of 30-day major bleeding and mortality. Results Major bleeding rates in patients treated with heparin plus GPI were higher versus bivalirudin monotherapy (5.7% vs. 3.0%, p Conclusions Major bleeding is a powerful independent predictor of 30-day mortality in patients with ACS managed invasively. Several factors independently predict major bleeding, including treatment with heparin plus GPI compared with bivalirudin monotherapy. Knowledge of these findings might be useful to reduce bleeding risk and improve outcomes in ACS.

The evolution of the management of acute myocardial infarction (MI) has been one of the crowning achievements of modern medicine. At the turn of the twentieth century, MI was an often-fatal condition. Prolonged bed rest served as the principal treatment modality. Over the past century, insights into the pathophysiology of MI revolutionized approaches to management, with the sequential use of surgical coronary artery revascularization, thrombolytic therapy, and percutaneous coronary intervention (PCI) with primary coronary angioplasty, and placement of intracoronary stents. The benefits of prompt revascularization inspired systems of care to provide rapid access to PCI. This review provides a historical context for our current approach to primary PCI for acute MI.

The aim of this study is to determine the diagnostic value of cardiac magnetic resonance imaging (CMR) with late gadolinium enhancement (LGE), cine imaging, and resting first-pass perfusion (FPP) in the evaluation for ischemic (IC) versus non-ischemic (NIC) cardiomyopathy in new onset heart failure with reduced (≤40%) left ventricular ejection fraction (HFrEF). A retrospective chart review analysis identified 83 patients between January 2009 and June 2012 referred for cardiac magnetic resonance imaging (CMR) evaluation for new onset HFrEF with coronary angiography performed within 6 months of CMR. The diagnosis of IC was established using Felker’s criteria on coronary angiography. CMR sequences were evaluated for the presence of patterns suggestive of severe underlying coronary artery disease as the cause of HFrEF (subendocardial and/or transmural LGE, regional wall motion abnormality on cine, regional hypoperfusion defect on resting FPP). Discriminative power was assessed using receiver operator characteristics curve analysis. Coronary angiography identified 36 patients (43%) with IC. Presence of subendocardial and/or transmural LGE alone demonstrated good discriminative power (c-statistic 0.85, 95% confidence interval 0.76–0.94) for the diagnosis of IC. The presence of an ischemic pattern on both LGE and cine sequences resulted in a specificity of 87% for the diagnosis of IC, while the absence of an ischemic pattern on both LGE and cine sequences resulted in a specificity of 94% for the diagnosis of NIC. Addition of resting FPP on a subset of patients did not improve diagnostic values. In conclusion, CMR has potential value in the diagnostic evaluation of IC versus NIC.

The optimal revascularization strategy in patients with acute coronary syndrome (ACS) and proximal left anterior descending (pLAD) coronary artery lesions is not well defined. The aim of this study was to compare the outcomes of ACS patients with pLAD culprit lesions receiving percutaneous coronary intervention (PCI) vs coronary artery bypass graft (CABG).The ACUITY trial was a multicenter, prospective trial of patients with ACS treated with an early invasive strategy. Major adverse cardiac event (MACE; defined as death, myocardial infarction [MI], and repeat revascularization) and stroke were compared at 30 days and 1 year between PCI and CABG in patients with significant stenosis of the pLAD undergoing revascularization. Postprocedural major bleeding was evaluated at 30 days.Among patients with a significant pLAD stenosis (n = 842), a total of 562 (66.7%) underwent PCI and 280 (33.3%) underwent CABG. Baseline characteristics, including age, sex, diabetes, and TIMI risk score, were well matched between groups; however, patients undergoing PCI were more likely to have had previous CABG (21.9% vs 6.4%; P.001). Death, MI, MACE, and stroke rates did not differ between groups at 1 year. PCI patients had lower bleeding rates (8.1% vs 52.4%; P.001) and blood product transfusion at 30 days (4.5% vs 41.3%; P.001), but higher rates of unplanned revascularization at 1 year (12.7% vs 5.2%; P.01). These results were consistent in patients with single vs multivessel disease and in diabetics vs non-diabetics.Among ACS patients with pLAD culprit lesions, an initial revascularization strategy of PCI compared with CABG yields similar 1-year death, MI, and MACE rates, although unplanned revascularization is more common after PCI.

More than 20 years of misconceptions derailed acceptance of reperfusion therapy for acute myocardial infarction (AMI). Cardiologists abandoned reperfusion for AMI using fibrinolytic therapy, explored in 1958, because they no longer attributed myocardial infarction to coronary thrombosis. Emergent aortocoronary bypass surgery, pioneered in 1968, remained controversial because of the misconception that hemorrhage into reperfused myocardium would result in infarct extension. Attempts to limit infarct size by pharmacotherapy without reperfusion dominated research in the 1970s. Myocardial necrosis was assumed to progress slowly, in a lateral direction. At least 18 hours was believed to be available for myocardial salvage. Afterload reduction and improvement of the microcirculation, but not reperfusion, were thought to provide the benefit of streptokinase therapy. Finally, coronary vasospasm was hypothesized to be the central mechanism in the pathogenesis of AMI. These misconceptions unraveled in the late 1970s. Myocardial necrosis was shown to progress in a transmural direction, as a "wave front," beginning with the subendocardium. Reperfusion within 6 hours salvaged a subepicardial ischemic zone in experimental animals. Acute angiography provided in vivo evidence of the high incidence of total coronary occlusion in the first hours of AMI. In 1978, early reperfusion by transluminal recanalization was shown to be feasible. The pathogenetic role of coronary thrombosis was definitively established in 1979 by demonstrating that intracoronary streptokinase rapidly restored flow in occluded infarct-related arteries, in contrast to intracoronary nitroglycerine which rarely did. The modern reperfusion era had dawned.

Background— The preferred revascularization strategy for diabetic patients with acute coronary syndromes and multivessel coronary artery disease is uncertain. We evaluated the outcomes of diabetic patients with moderate and high-risk acute coronary syndrome and multivessel disease managed with percutaneous coronary intervention (PCI) versus coronary artery bypass grafting (CABG). Methods and Results— Among 13 819 moderate and high-risk acute coronary syndrome patients enrolled in the Acute Catheterization and Early Intervention Triage Strategy (ACUITY) trial, 1772 diabetic patients had multivessel disease with left anterior descending artery involvement and were managed by PCI (n=1349) or CABG (n=423). Propensity scoring was applied to adjust for differences in baseline clinical and angiographic characteristics, yielding a total of 326 matched patients (163 managed by PCI and 163 managed by CABG). At 30 days, treatment with PCI compared with CABG was associated with lower rates of major bleeding (15.3% versus 55.6%; P P P P =0.03). At 1 year PCI was associated with higher rates of repeat revascularization procedures (19.5% versus 5.2%; P =0.0001), with nonsignificantly different rates of myocardial infarction, stroke, and death at either 30 days or 1 year. Conclusions— In the large-scale ACUITY trial, diabetic patients with acute coronary syndrome and multivessel disease treated with PCI rather than CABG had less bleeding and acute kidney injury, greater need for repeat revascularization procedures, and comparable rates of myocardial infarction, stroke, and death through 1-year follow-up. Clinical Trial Registration— URL: http://www.clinicaltrials.gov . Unique identifier: NCT00093158.