Faculty Bibliography

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).

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.

The purpose of this study was to determine international patterns of blood transfusion in patients with acute coronary syndrome (ACS). Previous studies showed geographic heterogeneity in some aspects of ACS care. Data for variability in the use of blood transfusion in ACS management are limited. Pooled data from 3 international randomized trials of patients with non-ST-segment elevation ACS (n = 23,906) were analyzed to determine the association between non-United States (US) location and blood transfusion after stratifying by the use of invasive procedures. The analysis adjusted for differences in patient characteristics and was repeated using a 2-stage mixed-model approach and in patients who underwent in-hospital coronary artery bypass grafting. Compared with US patients, both unadjusted and adjusted hazards for blood transfusion were significantly lower in non-US patients who did not undergo invasive procedures (unadjusted hazard ratio [HR] 0.23, 95% confidence interval [CI] 0.17 to 0.33; adjusted HR 0.20, 95% CI 0.14 to 0.28). This was also true in non-US patients who underwent invasive procedures (unadjusted HR 0.34, 95% CI 0.27 to 0.44; adjusted HR 0.31, 95% CI 0.23 to 0.42). Results were similar in both validation analyses. In conclusion, there was substantial international variation in blood transfusion use in patients with ACS. These results, along with the controversy regarding the appropriate use of transfusion in patients with coronary heart disease, emphasize the need for understanding the role of blood transfusion in the management of patients with ACS and factors that influence transfusion decisions.

BACKGROUND:Bleeding and blood transfusion are associated with increased morbidity and mortality among patients with non-ST-segment elevation acute coronary syndromes (NSTE ACS); however, the economic consequences of these complications are not well defined. We sought to determine the relationship between bleeding, blood transfusion, and measures of costs among patients with non-ST-segment elevation ACS. METHODS:We analyzed data from the economic substudy of the GUSTO IIb trial (n = 1235) to determine the relationship between bleeding; transfusion; and hospital costs, physician costs, total costs, and length of stay. Linear regression models were developed to determine the cost implications of each bleeding and transfusion event. RESULTS:Of the patients in the economic substudy of GUSTO IIb, 36.8% (n = 455) experienced a bleeding event. As bleeding severity increased, there was a stepwise increase in length of stay (no bleeding 5.4 days, mild bleeding 6.9 days, moderate bleeding 15.0 days, severe bleeding 16.4 days; P < .01) and unadjusted total costs (no bleeding $14,282, mild $21,674, moderate $45,798, severe $66,564; P < .01). After adjustment for baseline differences among patients, each moderate or severe bleeding event increased costs by $3770 and each transfusion event increased costs by $2080. Further modeling demonstrated that the increase in costs was driven by increases in length of stay. CONCLUSIONS:Bleeding and transfusion are associated with increased resource use among patients with NSTE ACS. These data suggest that strategies that reduce both ischemia and the risk for bleeding have the potential to produce important reductions in the costs of care for patients with NSTE ACS.

AIMS/OBJECTIVE:Non-invasive risk stratification of low- and intermediate-risk non-ST-elevation acute coronary syndromes (NSTE ACS) patients has been recommended, but limited data exist about the variation in clinical practice of stress testing in these patients and the impact of such testing on their outcomes. METHODS AND RESULTS/RESULTS:Patients with NSTE ACS enrolled in the GUSTO IIb (Global Use of Strategies To Open occluded coronary arteries in acute coronary syndromes-IIb) trial (n = 8011) were analysed to evaluate patterns of stress testing in US and non-US patients and to further evaluate the clinical characteristics, procedure use, and outcomes of patients who underwent stress testing compared with those who did not. Stress testing was performed in 1878 (24%) patients. Compared with patients not undergoing stress testing, those undergoing stress testing had low-risk characteristics and significantly lower death (0.6% vs. 4.8%), and death or myocardial infarction (MI, 3.9% vs. 11%) rates at 30 days. Stress testing was performed as often after as before coronary angiography. Importantly, stress testing was helpful in stratifying patients into low (equivocal or negative test) or high (positive test) risk groups (30 day death 3.1% vs. 5%). Stress testing was performed more often in non-US than US patients, and US patients were 3.5 times more likely to undergo imaging as part of stress testing. However, the risks of 30-day death or MI; 6-month death, MI or revascularization; and 1-year death did not differ between US and non-US patients. CONCLUSION/CONCLUSIONS:Stress testing is commonly performed in low-risk NSTE ACS patients and provides modest additional prognostic information in this cohort. Significant geographical variation exists in the use of stress testing. Therefore, in the current practice environment where cardiac catheterization is often the first diagnostic modality used in patients with NSTE ACS, the role of non-invasive testing both before and after invasive procedure is in need of further study.

OBJECTIVES/OBJECTIVE:To describe the association between transfusion and outcomes as a function of nadir hematocrit (HCT) in patients with non-ST-segment elevation acute coronary syndromes (NSTE ACS). BACKGROUND:The adverse outcomes associated with transfusion in NSTE ACS is uncertain and may vary by nadir HCT of the transfused. METHODS:Using data from 44242 patients with NSTE ACS in 400 US hospitals in the CRUSADE initiative (January 2004-December 2005), we describe blood transfusion as a function of nadir HCT and associated outcomes across nadir HCT groups (<or=24%, 24.1%-27%, 27.1%-30%, >30%). We further explore patient and process variation across hospital quartiles defined by transfusion use. RESULTS:Overall, 22.2% of patients with NSTE ACS are anemic and 10.4% receive a blood transfusion during their care. Likelihood of transfusion rose from 1% when nadir HCT was >30% to 70% when nadir HCT was <or=24%. The threshold for transfusion is a median nadir HCT of 25.7% (interquartile range 23.8%-27.5%). Although nadir HCT of transfused remains constant across quartiles of transfusion use, occurrence of bleeding increases. Inhospital mortality is higher in lower nadir HCT groups. In those with a nadir HCT of <or=24%, transfusion tended to have a beneficial impact on mortality (HCT <or=24% adjusted odds ratio [OR] 0.68 [0.45-1.02]). In the median range where transfusion occurs, transfusion had a neutral impact on mortality (HCT 24%-27% adjusted OR 1.01 [0.79-1.30]). Although rare, those transfused with nadir HCT of 27% to 30% (adjusted OR 1.18 [0.92-1.50]) or HCT of >30% (adjusted OR 3.47 [2.30-5.23]) had higher mortality. CONCLUSION/CONCLUSIONS:Anemia and transfusion are common in the care of NSTE ACS. The observed association between transfusion and adverse outcomes is neutral in the nadir HCT range where transfusions are most often given and trends strongly to benefit when nadir HCT is <or=24%. Although reassuring, randomized trials are needed to confirm the safety of transfusion in NSTE ACS. In the meantime, avoiding the need for transfusion is the best approach.

This paper, developed from the proceedings of the 2007 Platelet Colloquium, considers emerging constructs in platelet biology, preclinical models of thrombosis, and their potential application to the development of platelet-directed pharmacotherapies. Discussed first is the developmental biology of platelets, including megakaryocyte maturation, and the role of apoptotic and growth factors and other proteins in thrombopoiesis. A brief overview of current methods and observations from platelet proteomic analyses is also presented, illustrating the complex interplay of genes, gene expression, protein expression, and protein modification in various atherothrombotic phenotypes. The factor Xa-platelet interface is used as a working model for discussion of anticoagulants as platelet antagonists, highlighting the importance of receptor expression, substrate binding kinetics, platelet subpopulations, and cofactors in thrombosis. Finally, we discuss the use of emerging technologies--such as intravital microscopy and ex vivo perfusion chambers--as translatable platforms for investigating the role of platelets and their pharmacologic inhibition in human health and disease.

BACKGROUND:Guidelines for the management of high-risk non ST-segment elevation acute coronary syndrome (NSTE ACS) recommend antithrombotic and antiplatelet therapy combined with an early invasive strategy. While this strategy reduces ischemic complications, it places patients at risk for bleeding complications. OBJECTIVE:We sought to provide a narrative review of the risk factors for bleeding, risks associated with bleeding and strategies to prevent bleeding complications. METHODS:A comprehensive literature review was performed to identify relevant evidence. RESULTS/CONCLUSIONS/CONCLUSIONS:Bleeding complications in NSTE ACS are associated with adverse events and higher mortality. Prevention of bleeding complications can be achieved through judicious dosing of medications, the use of antithrombotic agents associated with a lower bleeding risk and use of the radial artery approach in patients requiring coronary intervention. Future work should focus on delineating the mechanisms underlying the bleeding-mortality relationship and developing a better understanding of the tradeoff between efficacy and safety.