Faculty Bibliography

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.

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.

Evaluation of: Schachinger V, Erbs S, Elsasser A et al.: Intracoronary bone marrow-derived progenitor cells in acute myocardial infarction. N. Engl. J. Med. 355, 1210-1221 (2006). The Reinfusion of Enriched Progenitor cells And Infarct Remodeling in Acute Myocardial Infarction (REPAIR-AMI) trial, the largest randomized, placebo-controlled trial of stem cell therapy in acute myocardial infarction, studied the efficacy of the intracoronary delivery of bone marrow mononuclear cells (BMCs) versus placebo in patients with acute ST-segment elevation myocardial infarction following successful percutaneous coronary intervention. At 4 month follow-up, patients treated with BMCs had a significant improvement in left ventricular ejection fraction compared with placebo (+5.5 vs +3.0%, absolute difference +2.5%). In addition, treatment with BMCs was associated with a statistically significant reduction in adverse clinical events at 1 year follow-up. Despite these promising findings, other studies have shown mixed results and several unresolved clinical and physiological issues remain. Key findings from ongoing basic and clinical research will define the future role of stem cell therapy for acute myocardial infarction.

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.