Faculty Bibliography

Antiplatelet therapy is the cornerstone of management in acute coronary syndromes (ACS) and percutaneous coronary intervention. Combination therapy with aspirin and clopidogrel reduces the risk of death, myocardial infarction, or stroke in ACS but increases the risk of major bleeding, which studies indicate is 1%-4% higher when clopidogrel is added to aspirin. Given the association between bleeding and adverse outcomes, minimizing bleeding risk is a clinical priority. This review outlines strategies to reduce both acute and chronic bleeding risk with aspirin and clopidogrel and focuses on dosing of concomitant therapies, vascular access techniques, and mitigating the bleeding risk associated with coronary artery bypass grafting surgery.

Guidelines support percutaneous coronary intervention (PCI) of the noninfarct-related artery during primary PCI for ST-segment elevation myocardial infarction (STEMI) in patients with hemodynamic compromise; however, in patients without hemodynamic compromise, PCI of the noninfarct-related artery is given a class III recommendation. We analyzed the National Cardiovascular Data Registry (n = 708,481 admissions, 638 sites) to determine the prevalence, predictors, and in-hospital outcomes of primary multivessel PCI from 2004 to 2007. Patients with STEMI and multivessel coronary artery disease who were undergoing primary PCI were identified (n = 31,681). After excluding the patients treated with staged PCI (n = 2,745), 10.8% (n = 3,134) of the remaining population (n = 28,936) were treated with multivessel PCI. Patients undergoing multivessel PCI were at higher risk and were more likely to be in cardiogenic shock. The overall in-hospital mortality rates were greater in patients undergoing multivessel PCI (7.9% vs 5.1%, p <0.01). Among patients with STEMI and cardiogenic shock (n = 3,087), those receiving multivessel PCI had greater in-hospital mortality (36.5% vs 27.8%; adjusted odds ratio 1.54, 95% confidence interval 1.22 to 1.95). In conclusion, these data suggest that performing multivessel PCI during primary PCI for STEMI does not improve short-term survival even for patients with cardiogenic shock. These findings suggest the need for definitive studies to evaluate the utility of noninfarct-related artery PCI among patients with STEMI.

Bleeding complications after percutaneous coronary interventions (PCI) are a significant clinical problem associated with worse patient outcomes, including mortality. A number of studies have demonstrated that the majority of bleeding complications in patients undergoing PCI are related to access-site bleeding. Employing the transradial artery approach to PCI markedly reduces these bleeding rates. The reductions in bleeding and transfusions from employing the transradial approach may be associated with improved survival in PCI patients. Despite these data, the prevalence of transradial PCI remains low and its adoption by operators has been slow to increase. Growing data to support the superior clinical outcomes with radial artery PCI, coupled with improved awareness of this data, may lead to increases in its adoption and improved clinical outcomes and mortality after PCI.

BACKGROUND:Bleeding in patients undergoing percutaneous coronary intervention (PCI) is associated with increased morbidity, mortality, length of hospitalization, and cost. We identified baseline clinical characteristics associated with bleeding complications after PCI and developed a simplified, clinically useful algorithm to predict patient risk. METHODS AND RESULTS/RESULTS:Data were analyzed from 302 152 PCI procedures performed at 440 US centers participating in the National Cardiovascular Data Registry. As defined by the National Cardiovascular Data Registry, bleeding required transfusion, prolonged hospital stay, and/or a drop in hemoglobin >3.0 g/dL from any location, including percutaneous entry site, retroperitoneal, gastrointestinal, genitourinary, and other/unknown location. Bleeding complications occurred in 2.4% of patients. From the best-fitting model consisting of 15 clinical elements associated with post-PCI bleeding in a random 80% training cohort, we developed a parsimonious risk algorithm. Predictors of bleeding included age, gender, previous heart failure, glomerular filtration rate, peripheral vascular disease, no previous PCI, New York Heart Association/Canadian Cardiovascular Society Functional Classification class IV heart failure, ST-elevation myocardial infarction, non-ST-elevation myocardial infarction, and cardiogenic shock. The parsimonious model was validated in the remaining 20% of the population (c-statistic, 0.72) and in clinically relevant subgroups of patients. This simplified model was used to derive a clinical risk algorithm, with larger numbers corresponding with greater risk. In 3 categories, bleeding rates were greater in patients with higher estimates (<or=7, 0.7%; 8 to 17, 1.8%; >or=18, 5.1%). CONCLUSIONS:This report identifies baseline clinical factors associated with bleeding and proposes a clinically useful algorithm to estimate bleeding risk. This model is potentially actionable in altering therapeutic decision making and improving outcomes in patients undergoing PCI.

BACKGROUND: Treatments for non-ST-segment-elevation myocardial infarction (NSTEMI) reduce ischemic events but increase bleeding. Baseline prediction of bleeding risk can complement ischemic risk prediction for optimization of NSTEMI care; however, existing models are not well suited for this purpose. METHODS AND RESULTS: We developed (n=71 277) and validated (n=17 857) a model that identifies 8 independent baseline predictors of in-hospital major bleeding among community-treated NSTEMI patients enrolled in the Can Rapid risk stratification of Unstable angina patients Suppress ADverse outcomes with Early implementation of the ACC/AHA guidelines (CRUSADE) Quality Improvement Initiative. Model performance was tested by c statistics in the derivation and validation cohorts and according to postadmission treatment (ie, invasive and antithrombotic therapy). The CRUSADE bleeding score (range 1 to 100 points) was created by assignment of weighted integers that corresponded to the coefficient of each variable. The rate of major bleeding increased by bleeding risk score quintiles: 3.1% for those at very low risk (score < or = 20); 5.5% for those at low risk (score 21-30); 8.6% for those at moderate risk (score 31-40); 11.9% for those at high risk (score 41-50); and 19.5% for those at very high risk (score >50; P(trend) <0.001). The c statistics for the major bleeding model (derivation=0.72 and validation=0.71) and risk score (derivation=0.71 and validation=0.70) were similar. The c statistics for the model among treatment subgroups were as follows: > or = 2 antithrombotics=0.72; <2 antithrombotics=0.73; invasive approach=0.73; conservative approach=0.68. CONCLUSIONS: The CRUSADE bleeding score quantifies risk for in-hospital major bleeding across all postadmission treatments, which enhances baseline risk assessment for NSTEMI care.

OBJECTIVES: We sought to examine angiographic and clinical outcomes with sirolimus-eluting stents (SES) in total coronary occlusion (TCO) revascularization. BACKGROUND: Despite evaluation of drug-eluting stents beyond approved indications, few studies have evaluated their clinical benefit in TCO revascularization. METHODS: Among 15 centers in North America, 200 consecutive TCO patients (78.8% >6 weeks TCO age) were enrolled for treatment with SES. The primary end point was 6-month angiographic binary restenosis within the treated segment. RESULTS: Patient characteristics included: diabetes, 24.5%; prior infarction, 33.5%; and stent length, 45.9 mm median (quartile 1, 30.2 mm; quartile 2, 62.1 mm). A total of 199 patients (99.5%) were treated with SES, and procedural success was 98.0%. The 6-month binary restenosis rates were 9.5% in-stent, 12.4% in-segment, and 22.6% in-"working length" representing the entire treatment segment. Rates of 1-year target lesion revascularization, myocardial infarction, and target vessel failure were 9.8%, 1.0%, and 10.9%, respectively. Stent thrombosis occurred in 2 patients (1.0%). Using logistic regression modeling with propensity score adjustment, the absolute reduction in binary restenosis with SES compared with a historical bare-metal stent control was 37.7% (95% confidence interval [CI]: 27.2% to 48.3%, p < 0.001; odds ratio: 0.17, 95% CI: 0.09 to 0.30, p < 0.0001). Among 32 patients (16%) identified with stent fracture, target lesion revascularization was more common than patients without fracture (25.0% vs. 6.7%, p = 0.005). CONCLUSIONS: Despite greater lesion complexity than prior TCO trials, percutaneous revascularization with SES appears safe and results in substantial reductions in angiographic restenosis and failed patency and a low rate of repeat revascularization. These findings support the use of SES in TCO revascularization. (The ACROSS/TOSCA Trial; NCT00378612).

OBJECTIVE:To evaluate the burden of major bleed in patients with non-ST segment elevation acute coronary syndromes (NSTE ACS) receiving injectable anticoagulation from the hospital perspective. METHODS:Retrospective analysis of inpatient medical and pharmacy data from the Premier Perspective Comparative Database between 1/1/2003 and 3/31/2006. Hospitalized patients aged >or=18 years with a diagnosis of UA or NSTEMI who received an injectable anticoagulant agent during the same hospital stay were stratified into two cohorts: those who experienced a major bleed during hospitalization and those who did not, defined by the presence of >or=1 pre-specified ICD-9 codes. Length of hospital stay (LOS), inpatient mortality, 30-day readmissions, and hospitalization costs over 30 days were assessed between the cohorts using statistical models to control for covariates which may have impacted the outcomes. RESULTS:Patients with a major bleed had significantly longer length of stay (13.8 days vs 5.6 days), higher readmission rates (31.3% vs 14.7%), and increased all-cause mortality (15.0% vs 4.5%) compared with patients who did not bleed. After controlling for covariates, major bleeding was significantly associated with increased length of stay, readmission rate, and mortality. Adjusted costs were $13,856 higher on average for patients with a major bleed (95% CI: $13,828-$18,884; p < 0.0001). Subanalyses conducted on patients aged >or=65 years and those undergoing invasive procedures demonstrated higher occurrence of bleed than the general population and a similar impact on outcomes assessed. CONCLUSION/CONCLUSIONS:In conclusion, the study showed that patients with UA or NSTEMI who experience a major bleed have significantly longer hospital stays, higher readmission rates, increased costs, and increased mortality than those without a major bleed. These data emphasize the importance of considering the safety profile in context of the efficacy of the recommended agents. The findings from this study are limited by the retrospective study design and certain endpoints, such as readmissions, may have been underreported.

Published mortality models for percutaneous coronary intervention (PCI), including the Clinical Outcomes Assessment Program (COAP) model, have not considered the effect of out-ofhospital cardiac arrest. The primary objective of this study was to determine if the inclusion of out-of-hospital cardiac arrest altered the COAP mortality model for PCI. The COAP PCI database contains extensive demographic, clinical, procedural and outcome information, including out-of-hospital cardiac arrest, which was added to the data collection form in 2006. This study included 15,586 consecutive PCIs performed in 31 Washington State hospitals in 2006. Using development and test sets, the existing COAP PCI logistic regression mortality model was examined to assess the effect of out-of-hospital arrest on in-hospital mortality. Overall, 2% of individuals undergoing PCI had cardiac arrest prior to hospital arrival. Among 8 hospitals with PCI volumes < 120 cases per year, 4 had cardiac arrest volumes that exceeded 10% of total volume, whereas none of the centers with > 120 cases per year did. In-hospital mortality was 19% in the arrest group and was 1.0% in remaining procedures (p < 0.0001). In the new multivariate model, out-of-hospital cardiac arrest was highly associated with mortality (odds ratio = 5.50; 95% confidence interval [CI] = 3.28-9.25). When evaluated in the test set, the new model had excellent discrimination (c-statistic = 0.89; 95% CI = 0.85-0.93). Out-of-hospital cardiac arrest is an important determinant of risk-adjusted in-hospital mortality for PCI, particularly for hospitals with low volumes and relatively high volumes of cardiac arrest cases.

Definitions of bleeding must be considered when evaluating results of clinical trials. Assessments of bleeding impact based on clinical criteria may be more relevant to patient outcomes than those based on simple laboratory measures like an isolated change in hemoglobin, that do not appear to affect patient care. The risk of excessive bleeding in patients who receive antiplatelet and antithrombotic therapy is related to a combination of patient characteristics (older age, female sex, impaired renal function), and delivery factors (excessive dosing, stacking of anticoagulants). Investigators should justify components of bleeding endpoints as being clinically meaningful, sufficiently frequent in the study population, and affected by the intervention.