Please see http://atvb.ahajournals.org/site/misc/ ATVB_in_Focus.xhtml for all articles published in this series. Comparison of the Pharmacological Properties of the NOACs With Those of WarfarinAs outlined in Abstract-The non-vitamin K antagonist oral anticoagulants (NOACs) are replacing warfarin for many indications. These agents include dabigatran, which inhibits thrombin, and rivaroxaban, apixaban, and edoxaban, which inhibit factor Xa. All 4 agents are licensed in the United States for stroke prevention in atrial fibrillation and for treatment of venous thromboembolism and rivaroxaban and apixaban are approved for thromboprophylaxis after elective hip or knee arthroplasty. The NOACs are at least as effective as warfarin, but are not only more convenient to administer because they can be given in fixed doses without routine coagulation monitoring but also are safer because they are associated with less intracranial bleeding. As part of a theme series on the NOACs, this article (1) compares the pharmacological profiles of the NOACs with that of warfarin, (2) identifies the doses of the NOACs for each approved indication, (3) provides an overview of the completed phase III trials with the NOACs, (4) briefly discusses the ongoing studies with the NOACs for new indications, (5) reviews the emerging real-world data with the NOACs, and (6) highlights the potential opportunities for the NOACs and identifies the remaining challenges.

Importance: Future funding for new treatments in venous thromboembolism will be guided by cost-utility analyses. There is little available information on the utility of acute venous thromboembolism, limiting the validity of economic analyses. Objective: To measure the quality of life in the health states relating to thromboembolism cost-utility analyses. Design: A prospective cohort study. Setting: A single-center, university-affiliated thrombosis clinic. Participants: Two hundred sixteen thrombosis clinic patients with a history of lower limb deep vein thrombosis (DVT) or pulmonary embolism (PE). Exposures: Participantsconsentedtotakeastandardgamble interview. Each participant rated the quality of life in acute DVT, acute PE, and bleeding complication health states. Main Outcomes and Measures: The standard gamble measured quality of life (utility value) for acute DVT, acute PE, major intracranial bleeding event, minor intracranial bleeding event, and gastrointestinal bleeding event. Results: Two hundred fifteen responses were included in the analysis. Twenty-six percent had experienced both PE and DVT; 54%, DVT alone; and 20%, PE alone. Fortytwo percent had experienced more than 1 episode of thrombosis, and 23% had had cancer-associated thrombosis. We found the median utility for acute DVT was 0.81 (interquartile range [IQR], 0.55-0.94); acute PE, 0.75 (IQR, 0.45-0.91); major intracranial bleeding event, 0.15 (IQR, 0.00-0.65); minor intracranial bleeding event, 0.75 (IQR, 0.55-0.92); and gastrointestinal bleeding event, 0.65 (IQR, 0.15-0.86). The median length of symptoms for DVT or PE was 1 week (IQR, Ͻ1-3 weeks). Conclusions and Relevance: To our knowledge, this is the largest published study on utilities in which the participants had personal experience of venous thromboembolism. We present unique information for economic analyses but have also identified future challenges for research in this area. Our summary results differ from those previously published, and we found wide variation in individual responses.

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Objective: To appraise the evidence on the diagnostic accuracy of CT pulmonary angiography and the prognostic value of a negative CT pulmonary angiogram in the diagnosis of pulmonary embolism. Methods: Medline, EMBASE, and grey literature were systematically searched by two researchers. Any study which compared CT pulmonary angiography to an acceptable reference standard or prospectively followed up a cohort of patients with a normal CT pulmonary angiogram was included. Study methods were appraised independently by two researchers, and data were extracted independently by three researchers. Results: Thirteen diagnostic and 11 follow up studies were identified. Studies varied in prevalence of pulmonary embolism (19-79%), patient groups, and method quality. Few studies recruited unselected emergency department patients. There was heterogeneity in the analysis of sensitivity (53 to 100%), specificity (79 to 100%), and false negative rate (1.0 to 10.7%). The pooled false negative rate of combined negative CT pulmonary angiography and negative deep vein thrombosis testing was 1.5% (95% CI 1.0 to 1.9%). Conclusion: Diagnostic studies give conflicting results for the diagnostic accuracy of CT pulmonary angiography. Follow up studies show that CT pulmonary angiography can be used in combination with investigation for deep vein thrombosis to exclude pulmonary embolism.T he diagnosis of pulmonary embolism is challenging as symptoms of pulmonary embolism are varied and range from mild, non-specific lethargy or breathlessness, to collapse and cardiac arrest.1-3 Recurrent pulmonary embolism is associated with a case mortality of 26%. 4 Early diagnosis is essential as even patients with minor symptoms are at risk of recurrent pulmonary emboli.The combination of a normal D-dimer concentration and low clinical probability score 5-7 provides a robust screening method, facilitating exclusion of pulmonary embolism without diagnostic imaging. The PIOPED study 8 proposed combining ventilation-perfusion scanning with clinical probability for the safe exclusion and diagnosis in a subset of patients. This strategy does not exclude or diagnose pulmonary embolism in all suspected cases. The gold standard investigation-pulmonary angiography-is invasive and carries a recognised morbidity and mortality. Furthermore, a normal angiogram is associated with a 1.6% incidence of venous thromboembolism in the following year. 10Computed tomographic pulmonary angiography (CT pulmonary angiography) is increasingly used in the diagnosis of pulmonary embolism. CT has the advantage of imaging the entire thorax, facilitating the diagnosis of conditions mistaken for pulmonary embolism, such as pneumonia, aortic dissection, and malignancy.11 UK and US guidelines have planted CT among the basic investigations for pulmonary embolism.12 13 Attempts to evaluate the clinical utility of CT pulmonary angiography have been complicated by rapid advances in CT scanning technology, acceptance that angiography may not be the most appropriate reference standard, and he...