Faculty Bibliography

BACKGROUND:Major bleeding during an acute coronary syndrome (ACS) is associated with increased late ischemic events. Patients with bleeding are often discharged without antiplatelet therapy (AT). The association between discharge AT use and late ischemic outcomes among ACS patients with bleeding is uncertain. METHODS:We examined discharge AT use among 8,582 ACS patients with in-hospital bleeding from a total of 26,451 patients enrolled in 4 randomized trials. After adjusting for the propensity to receive AT, we compared 6-month postdischarge outcomes between patients discharged with and those discharged without AT. RESULTS:Almost 1 in 10 patients with bleeding was discharged without AT (n=826). Compared with those receiving discharge AT, those not receiving discharge AT had a higher risk of 6-month death, myocardial infarction, and stroke (14.3% vs 7.8%, propensity-adjusted hazard ratio [HR]=1.36, 95% confidence interval=1.01-1.85). Nonuse of AT at discharge was associated with worse outcomes among patients treated with percutaneous coronary intervention compared with those treated without it (adjusted HR=4.22 vs 1.13, interaction P=.0003). Discharge monotherapy was associated with worse outcomes than dual AT among patients receiving stents (adjusted HR=1.78, 95% CI=1.04-3.03). CONCLUSIONS:Bleeding occurred commonly among patients with ACS. AT was often not used in these patients at discharge, and lack of discharge AT was associated with an increased risk of 6-month ischemic events. These data raise the possibility that lack of AT use among patients with in-hospital bleeding may contribute to their excess risk of long-term ischemic outcomes.

The use of glycoprotein IIb/IIIa inhibitors (GPI) reduces ischemic events in patients undergoing percutaneous coronary intervention (PCI). However, the same properties that confer this benefit lead to an increased bleeding risk. Recent studies have shown a less robust net clinical benefit of GPI in the current era of routine thienopyridine and direct thrombin inhibitor use. To optimize the net clinical benefit of GPI, these agents need to be selectively used in patients most likely to benefit from their anti-ischemic effect, namely patients undergoing PCI for non-ST-segment elevation myocardial infarction, select patients undergoing primary PCI, and select patients undergoing PCI without appropriate pre-loading with a thienopyridine. Moreover, strategies to minimize bleeding should be applied in these patients and include shorter GPI infusions (in some patients), dose adjustments of heparin and GPI, careful access site management with more frequent use of the transradial approach, use of smaller sheaths, and identification of patients at high bleeding risk. This review provides an update of the current literature that supports these measures, an insight on the tailored use of GPI, and a potential direction for future research addressing combined antithrombotic therapies.

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.

BACKGROUND:Interest in the biology of endogenous progenitor cells (EPCs) continues to grow as evidence of their role in vascular repair mounts. EPC enumeration requires specialized laboratory techniques and is performed immediately after sample acquisition, limiting the clinical contexts in which EPC enumeration can be performed and the ability to increase sample sizes through multi-center participation. METHODS:We compared the numbers of EPCs enumerated in samples processed immediately after acquisition (n = 36) with EPCs enumerated in specimens stored for 24 hours or after cryopreservation of mononuclear cells (MNC) using two EPC identification strategies: cell surface marker expression (CD133/CD34) and aldehyde dehydrogenase activity (ALDH(br) cells). RESULTS:EPCs assessed in fresh samples correlated with EPCs enumerated after whole blood storage (r = 0.699 for CD133(+)CD34(+) cells, r = 0.880 for ALDH(br) cells, P < 0.005 and P < 0.0001, respectively) or mononuclear cryopreservation (r = 0.590 for CD133(+)CD34(+) cells, r = 0.894 for ALDH(br) cells, P < 0.0001 for each); however, correlation based on assessment of ALDH(br) cells was higher (P < 0.0003 for comparison of correlation coefficients). Initial results from a multi-site clinical trial suggest that EPC enumeration after mononuclear cell cryopreservation is feasible. CONCLUSION/CONCLUSIONS:EPC analysis based on ALDH activity is reproducible, even after extended whole blood storage or MNC cryopreservation.

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.

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.

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.