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.

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.