Faculty Bibliography

BACKGROUND:Bleeding among patients with acute myocardial infarction (AMI) is associated with worse long-term outcomes. Although the mechanism underlying this association is unclear, a potential explanation is that withholding antiplatelet therapies long beyond resolution of the bleeding event may contribute to recurrent events. METHODS AND RESULTS/RESULTS:We examined medication use at discharge, 1, 6, and 12 months after AMI among 2498 patients in the Prospective Registry Evaluating Myocardial Infarction: Events and Recovery (PREMIER) registry. Bleeding was defined as non-coronary artery bypass graft-related Thrombolysis of Myocardial Infarction major/minor bleeding or transfusion among patients with baseline hematocrit > or =28%. Logistic regression was used to evaluate the association between bleeding during the index AMI hospitalization and medication use. In-hospital bleeding occurred in 301 patients (12%) with AMI. Patients with in-hospital bleeding were less likely to be discharged on aspirin or thienopyridine (adjusted odds ratio=0.45; 95% CI, 0.31 to 0.64; and odds ratio=0.62; 95% CI, 0.42 to 0.91, respectively). At 1 month after discharge, although patients with in-hospital bleeding remained significantly less likely to receive aspirin (odds ratio=0.68; 95% CI, 0.50 to 0.92), use of thienopyridines in the 2 groups started to become similar. By 1 year, antiplatelet therapy use was similar among patients with and without bleeding. Postdischarge cardiology follow-up was associated with greater antiplatelet therapy use than either primary care or no clinical follow-up. CONCLUSIONS:Patients whose index AMI is complicated by bleeding are less likely to be treated with antiplatelet therapies during the first 6 months after discharge. Early reassessment of antiplatelet eligibility may represent an opportunity to reduce the long-term risk of adverse outcomes associated with bleeding.

BACKGROUND:Short-term use of clopidogrel plus aspirin among patients with acute coronary syndrome reduces ischemic events, but concerns about coronary artery bypass graft (CABG) surgery-related bleeding limit its early use. METHODS:Using data from 4,794 consecutive CABG procedures in the Duke Databank for Cardiovascular Disease (January 1999 to December 2003), we developed multivariable models for associations with CABG-related bleeding defined as reoperation for bleeding, red cell transfusion, and a composite of reoperation/transfusion/hematocrit drop>or=15%. We examined clopidogrel use<or=5 days versus no clopidogrel<or=5 days before CABG in each model. Models were adjusted for propensity for clopidogrel use<or=5 days. RESULTS:Of 4,794 CABG patients, 332 (6.9%) received clopidogrel<or=5 days before CABG, 127 (2.6%) had reoperation for bleeding, 3,277 (68.4%) received red cell transfusion, and 4,387 (91.5%) had the composite outcome. After adjustment, clopidogrel use<or=5 days was not significantly associated with reoperation (odds ratio [OR] 1.24, 95% CI 0.63-2.41) or the composite end point (OR 1.23, 95% CI 0.72-2.10). Clopidogrel<or=5 days was modestly associated with red cell transfusion (OR 1.40, 95% CI 1.04-1.89) but more weakly than other factors, including which surgeon performed the procedure. CONCLUSION/CONCLUSIONS:Clopidogrel administration<or=5 days before CABG was not significantly associated with reoperation for bleeding or a bleeding composite, and only weakly with red cell transfusion after surgery. The impact of withholding clopidogrel acutely in those for whom clopidogrel has proven benefits and the impact of delaying CABG to prevent bleeding among patients treated with clopidogrel should be viewed in the context of other stronger determinants of bleeding.

OBJECTIVES/OBJECTIVE:Our goal was to compare trends in the prevalence and outcomes of the radial and femoral approaches to percutaneous coronary intervention (PCI) in contemporary clinical practice. BACKGROUND:There are few current data on the use and outcomes of the radial approach to PCI (r-PCI) in clinical practice. METHODS:Data from 593,094 procedures in the National Cardiovascular Data Registry (606 sites; 2004 to 2007) were analyzed to evaluate trends in use and outcomes of r-PCI. Logistic regression was used to evaluate the adjusted association between r-PCI and procedural success, bleeding complications, and vascular complications. Outcomes in elderly patients, women, and patients with acute coronary syndrome were specifically examined. RESULTS:Although the proportion of r-PCI procedures has recently increased, it only accounts for 1.32% of total procedures (n = 7,804). Compared with the femoral approach, the use of r-PCI was associated with a similar rate of procedural success (adjusted odds ratio: 1.02 [95% confidence interval: 0.93 to 1.12]) but a significantly lower risk for bleeding complications (odds ratio: 0.42 [95% confidence interval: 0.31 to 0.56]) after multivariable adjustment. The reduction in bleeding complications was more pronounced among patients <75 years old, women, and patients undergoing PCI for acute coronary syndrome. CONCLUSIONS:The use of r-PCI is rare in contemporary clinical practice, but it is associated with a rate of procedural success similar to the femoral approach and with lower rates of bleeding and vascular complications, even among high-risk groups. These results suggest that wider adoption of r-PCI in clinical practice may improve the safety of PCI.

Cardiovascular procedures performed in the United States have more than tripled in the last decade, a trend that is expected to continue with the aging of the population, coupled with epidemics of obesity and diabetes mellitus. Helping to drive this increase are new medical devices that address conditions previously treated by medication alone. Many of these novel devices receive expedited reviews before Food and Drug Administration (FDA) approval and are rapidly adopted into clinical practice. However, recent high-profile cases involving potentially dangerous defects in widely used medical devices have increased concerns about the adequacy of premarket trials and postmarket surveillance in establishing the safety of these devices. In response to these concerns, the American College of Cardiology and the Duke Clinical Research Institute sponsored a 'think tank' of experts representing the industry, regulatory authorities, academic medicine, and professional societies to examine these concerns and propose possible solutions. This group examined case studies including drug-eluting stents and implantable cardioverter-defibrillators. Challenges inherent in the current system, including the difficulty of establishing accurate event rates for medical devices and potential disincentives for the industry to conduct comprehensive monitoring, were discussed. Possible solutions to these problems included improving and enforcing current regulations, considering creative study design strategies that link pre- and postmarket data, declaring postmarket surveillance a public health issue, creating financial incentives for participation in postmarketing studies, using more relevant animal models, encouraging postmortem device retrieval, and aligning professional societies with the FDA to evaluate breakthrough technologies and communicate findings to patients and clinicians

Antithrombotic therapy and invasive risk stratification in selected high-risk patients have improved outcomes from non-ST-segment elevation acute coronary syndromes (NSTE-ACS), but carry a risk of bleeding and blood transfusion. Although the true incidence of bleeding depends on the population studied (i.e. clinical trial vs. registry), the definition used, and the use of invasive procedures, it is becoming clear that bleeding is associated with an increased risk for adverse outcomes including myocardial infarction and death. Blood transfusion itself may carry a risk for ischaemic outcomes that is independent of bleeding. Therefore, therapies that provide an adequate level of anticoagulation to reduce ischaemia while simultaneously minimizing the risk of bleeding and transfusion have the potential to improve outcomes among patients with NSTE-ACS. Anticoagulants studied in recent clinical trials that have focused on bleeding reduction include fondaparinux and bivalirudin. In this review, we discuss the clinical trial evidence for these agents, the association between bleeding and clinical outcomes, the biology of blood transfusion and potential mechanisms underlying its association with adverse outcomes, and propose strategies to deal with bleeding complications. Future directions for research and clinical practice are also discussed.

Anemia is common among patients with coronary artery disease (CAD) and portends a higher risk of short- and long-term mortality, major adverse cardiac events, and bleeding complications. Blood transfusion has long been the cornerstone of therapy for anemia; however, its benefit in patients with CAD is controversial and the appropriate threshold for transfusion has been widely debated. In this review, we summarize the studies evaluating the impact of anemia in patients with CAD undergoing percutaneous coronary intervention and address several issues regarding the use of transfusion in anemic patients. In addition, we discuss alternative options for the management of anemia, such as the use of erythropoietin, aqueous oxygen, and hemoglobin-based oxygen carriers.

For patients undergoing percutaneous coronary intervention (PCI), bleeding complications are a major clinical concern. With advances in pharmacotherapy and devices over the past 2 decades, the risk of ischemic outcomes, such as myocardial infarction or death, has decreased. Bleeding complications have more recently become a clinical and research priority. Determining the incidence of and risk factors for bleeding is complicated by the multiple systems used to classify bleeding severity and report bleeding events. The origin of the data, clinical trials versus registries, also influences the incidence of reported bleeding events. Registry data suggest that risk of bleeding among patients undergoing PCI is higher in clinical practice than the incidence observed in clinical trials. Another clinical concern is the possible association between PCI-related bleeding complications and myocardial infarction, stroke, or death. Reduction in bleeding risk is a desirable goal that may potentially improve survival and increase comfort for patients undergoing PCI. Using strategies such as careful vascular access, alternative radial artery access, and modified antithrombotic regimen may reduce bleeding during PCI as well as improve patient outcomes.

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), and ST-elevation myocardial infarction (STEMI), as supported by recent updates to the ACC/AHA Guidelines. The authors have summarized findings from key clinical trials published in recent years that contribute to clinician's understanding of how best to optimize therapy. The goals for the management of NSTE-ACS and STEMI 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 a small molecule gylcoprotein [GP] IIb/IIIa inhibitor to a core regimen of aspirin, enoxaparin or other anticoagulants, and in most cases, clopidogrel) and/or that would direct clinicians toward percutaneous interventional strategies as the preferred modality include, but are not limited to the presence of one or more of the following: 1) elevatedcardiac markers (troponin and/or CK-MB); 2) age older than 65 years; 3) presence of ST-T-wave changes; 4) TIMI Risk Score >/= 5; 5) clinical instability in the setting of suspected 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. 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, angiotensin-converting enzyme (ACE) inhibitors and beta-blockers is also stressed as part of a comprehensive secondary cardioprotective strategy for patients with coronary heart disease.

Advances in the management of patients with acute coronary syndromes (ACS), specifically, the use of combined pharmacotherapy with antithrombotic and antiplatelet therapies and routine percutaneous coronary intervention (PCI), have greatly reduced rates of thrombotic outcomes and mortality in these patients. However, these same therapies also can increase the risk of bleeding and transfusion use, which are predictive of poor outcomes in patients with ACS. Accurate assessment of the risk-to-benefit ratio for any therapy depends on the use of clinically relevant, preferably standardized, definitions of endpoint events. Unfortunately, clinical trials of antithrombotic therapies have used various definitions for bleeding, most of which were originally developed for trials of fibrinolytic therapy in acute myocardial infarction (MI). These variations in bleeding definitions have complicated cross-study comparisons and assessments of drug class effects. Further, it is unclear whether these definitions remain clinically relevant in the era of routine PCI and aggressive antithrombotic therapy for ACS. Although an argument can be made for development of a standardized bleeding definition, a more prudent approach may be to develop standardized data elements, which can then be used to tailor bleeding definitions according to the goals of future clinical investigations.