Faculty Bibliography

This paper provides a comprehensive up-to-date review of the medical and invasive management of patients with non- ST-segment elevation acute coronary syndromes (NSTE-ACS). The authors have summarized findings from key clinical trials published recent years that contribute to clinicians' understanding of how best to optimize therapy. The goals for the management of NSTE-ACS are rapid and accurate risk stratification, appropriate and institution-specific triage to interventional versus medical strategies and optimal pharmacologic therapy--all of which provide for a smooth and seamless transition of care between the emergency department and the cardiology service. High-risk features or absolute treatment trigger criteria that support more aggressive medical therapy (i.e., addition of small-molecule GP IIb/IIIa inhibitor to a core regimen of aspirin, enoxaparin, and in most cases, clopidogrel) and/or that would direct clinicians toward percutaneous, mechanical/interventional strategies as the preferred modality include, but are not limited to, the presence of one or more of the following: (1) elevated cardiac markers (troponin and/or CK-MB); (2) elevated levels of inflammatory markers (particularly CRP > 3 microg/dl); (3) age > 65 years; (4) presence of ST-T wave changes; (5) TIMI Risk Score greater than or equal to 4; (6) diabetes; and/or (7) clinical instability in the setting of suspected NSTE-ACS.Specific clinical, ECG and/or biochemical trigger points modulate the aggressiveness of both the medical therapy and the propensity to perform early angiography with or without subsequent revascularization in patients with NSTE-ACS. Although additional refinements and changes in ACS management are still to come, evidence-based strategies suggest that prompt mechanical revascularization is associated with the best possible clinical outcomes, particularly for patients with high-risk features and in whom benefits of adjunctive, pharmacoinvasive antithrombotic therapies can be consolidated. Patient transfer for cardiac catheterization/percutaneous coronary intervention (PCI) is strongly recommended in patients who manifest high-risk features and/or aggressive treatment trigger criteria, so that this high-risk subgroup may receive definitive, interventional and/or cardiology-directed specialty care at appropriate sites of care. When available, interventional management is preferred in these patients. The importance of safe and effective anticoagulation in the spectrum of management strategies has been confirmed, and the evidence in support of enoxaparin and other antithrombotic agents has been reviewed. Dosing recommendations for enoxaparin use in the setting of PCI have been issued by the CATH Panel and have been summarized in this consensus report. Similar recommendations have been presented for the use of oral antiplatelet agents and GP IIb/IIIa antagonists. The addition of statins, ACE-inhibitors and beta-blockers is also stressed as part of a comprehensive secondary cardioprotective strategy for patients with coronary heart disease

BACKGROUND:Prior studies of atheroablation (directional atherectomy, rotational atherectomy and laser angioplasty) have demonstrated either no advantage or worse outcomes relative to conventional balloon angioplasty. Because these techniques are still required in a minority of patients, we hypothesized that the use of drug-eluting stents (DES) would minimize the rate of major adverse cardiac events (MACE) after atheroablation. METHODS:From 2,252 percutaneous coronary intervention procedures, 212 patients were extracted using case control matching and were analyzed to compare the rate of MACE across four groups (DES with atheroablation, bare-metal stent (BMS) with atheroablation, DES without atheroablation, bare-metal stent without atheroablation). A Cox proportional hazards model was constructed to determine predictors of MACE after adjustment for potential confounders. Internal validation was performed with bootstrapping. RESULTS:There were 36 patients, 42 patients, 63 patients and 71 patients in each of the groups, respectively. The incidence of 30-day and 6-month MACE was numerically lowest among patients who received DES after atheroablation, although the differences did not reach statistical significance (30-day MACE: 0% DES with atheroablation, 4.8% BMS with atheroablation, 3.2% DES without atheroablation, 8.5% BMS without atheroablation; 6-month MACE: 2.8% DES with atheroablation, 19.0% BMS with atheroablation, 6.4% DES without atheroablation, 16.9% BMS without atheroablation). After adjustment, the use of atheroablation was not a predictor of MACE. CONCLUSIONS:This study suggests that in situations where directional atherectomy, rotational atherectomy or laser angioplasty is required to optimize stenting, the use of DES can minimize MACE associated with atheroablation.

OBJECTIVE:To determine patterns and outcomes of drug-eluting stents (DES) use in clinical practice. BACKGROUND:DES are technology associated with superior outcomes. The initial limited availability and high cost of DES had the potential to influence their use. METHODS:Data from the American College of Cardiology-National Cardiovascular Data Registry were examined to describe the patterns of DES use in 408,033 percutaneous coronary intervention (PCI) procedures at 383 sites. Predictors of DES use were determined, and inhospital outcomes were examined. RESULTS:From April 2003 through December 2004, the proportion of procedures using DES increased from 19.7% to 78.2%. DES use increased across all patient groups and hospital types, but adoption was slower among older patients and those without health insurance. DES use varied among hospitals such that use was lower at rural and low-volume hospitals. Multivariable regression demonstrated a progressive decrease in the odds of DES use as age increased. White race, female sex, presence of insurance, diabetes mellitus, PCI of de novo lesion, PCI at a high volume center, and PCI at a suburban hospital were significant predictors of DES use. The availability of a second DES product did not influence the adoption patterns. Inhospital outcomes with DES were excellent. CONCLUSIONS:Access to DES was influenced by demographic, socioeconomic, and hospital characteristics. Further study is needed to determine if the availability of another DES platform or increased overall availability of DES impacts favorably on PCI practice patterns.

Limited data are available on the off-label use of drug-eluting stents (DESs) in clinical practice. We used data from the American College of Cardiology National Cardiovascular Data Registry to describe the rates and outcomes of DES use in 4 common off-label situations: ST-elevation myocardial infarction, in-stent restenosis, coronary artery bypass grafts, and chronic total occlusions. The rates of in-hospital adverse events for each off-label situation were determined and compared with the expected rates calculated from a validated model. From approval of DESs to the end of 2004, a total of 408,033 procedures involved placement of a DES. The use of DESs increased from 19.7% at the start of the study to 78.2% by the end of fourth quarter of 2004. Off-label use of DESs occurred in 24.1% of procedures. The rates of in-hospital adverse events with DES use in ST-elevation myocardial infarction, in-stent restenosis, coronary artery bypass grafting, and chronic total occlusions were lower than expected from the validated model. In conclusion, off-label use of DESs is common and is associated with a low rate of short-term adverse events. Randomized clinical trials are needed to confirm the efficacy of DESs in these clinical and angiographic settings. These data also highlight the importance of multicenter registries in tracking new technologies.

For many years, the traditional treatment for hospitalized patients in the United States who have developed anemia, whether associated with medical illness, surgical procedures or trauma, has been red blood cell transfusion, despite the absence of supporting data in many patient populations. Emerging evidence suggests that transfusions may, in fact, be associated with risk beyond commonly held concerns of microbial transmission and acute antigen-antibody reactions. The following overview represents a biological paradigm for understanding the relationship between medical illness, surgical procedures, inflammatory states, anemia, red blood cell transfusion and immunothrombotic phenomena among hospitalized patients.

OBJECTIVES/OBJECTIVE:The goal of this study was to determine the association between Thrombolysis In Myocardial Infarction (TIMI) and Global Use of Strategies to Open Occluded Coronary Arteries (GUSTO) bleeding and clinical outcomes. BACKGROUND:There are limited data on the relative utility of either scale at predicting clinical outcomes in patients with non-ST-segment elevation acute coronary syndromes (ACS). METHODS:Pooled data from two randomized trials of patients with ACS (n = 15,454) were analyzed to determine the association between TIMI and GUSTO bleeding and 30-day and 6-month death/myocardial infarction (MI) using Cox proportional hazards modeling that included bleeding as a time-dependent covariate. RESULTS:There was a stepwise increase in the adjusted hazard of 30-day death/MI with worsening GUSTO bleeding (hazard ratio [95% confidence interval], GUSTO mild 1.20 [1.05 to 1.37]; moderate 3.28 [2.88 to 3.73]; severe 5.57 [4.33 to 7.17]), and an increased risk with all three levels of TIMI bleeding (TIMI minimal 1.84 [1.63 to 2.08]; TIMI minor 1.64 [1.31 to 2.04]; major 1.45 [1.23 to 1.70]). When both bleeding scales were included in the same model, the risk with GUSTO bleeding persisted; however, the association between TIMI bleeding and outcome was no longer significant. CONCLUSIONS:Both scales identify ACS patients with bleeding complications at risk for adverse outcomes. In a model that included both definitions, the risk with GUSTO bleeding persisted while the risk with TIMI bleeding did not. This suggests that bleeding assessed with clinical criteria is more important than that assessed by laboratory criteria in terms of outcomes. Future clinical trials should consider using a combination of the GUSTO bleeding scale and the need for transfusion to assess bleeding complications.