Mark H. Eckman

Antithrombotic Therapy for Atrial Fibrillation Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines

BACKGROUND The risk of stroke varies considerably across different groups of patients with atrial fibrillation (AF). Antithrombotic prophylaxis for stroke is associated with an increased risk of bleeding. We provide recommendations for antithrombotic treatment based on net clinical benefit for patients with AF at varying levels of stroke risk and in a number of common clinical scenarios. METHODS We used the methods described in the Methodology for the Development of Antithrombotic Therapy and Prevention of Thrombosis Guidelines: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines article of this supplement. RESULTS For patients with nonrheumatic AF, including those with paroxysmal AF, who are (1) at low risk of stroke (eg, CHADS(2) [congestive heart failure, hypertension, age ≥ 75 years, diabetes mellitus, prior stroke or transient ischemic attack] score of 0), we suggest no therapy rather than antithrombotic therapy, and for patients choosing antithrombotic therapy, we suggest aspirin rather than oral anticoagulation or combination therapy with aspirin and clopidogrel; (2) at intermediate risk of stroke (eg, CHADS(2) score of 1), we recommend oral anticoagulation rather than no therapy, and we suggest oral anticoagulation rather than aspirin or combination therapy with aspirin and clopidogrel; and (3) at high risk of stroke (eg, CHADS(2) score of ≥ 2), we recommend oral anticoagulation rather than no therapy, aspirin, or combination therapy with aspirin and clopidogrel. Where we recommend or suggest in favor of oral anticoagulation, we suggest dabigatran 150 mg bid rather than adjusted-dose vitamin K antagonist therapy. CONCLUSIONS Oral anticoagulation is the optimal choice of antithrombotic therapy for patients with AF at high risk of stroke (CHADS(2) score of ≥ 2). At lower levels of stroke risk, antithrombotic treatment decisions will require a more individualized approach.

Perioperative Management of Antithrombotic Therapy: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines

BACKGROUND This guideline addresses the management of patients who are receiving anticoagulant or antiplatelet therapy and require an elective surgery or procedure. METHODS The methods herein follow those discussed in the Methodology for the Development of Antithrombotic Therapy and Prevention of Thrombosis Guidelines. Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines article of this supplement. RESULTS In patients requiring vitamin K antagonist (VKA) interruption before surgery, we recommend stopping VKAs 5 days before surgery instead of a shorter time before surgery (Grade 1B). In patients with a mechanical heart valve, atrial fibrillation, or VTE at high risk for thromboembolism, we suggest bridging anticoagulation instead of no bridging during VKA interruption (Grade 2C); in patients at low risk, we suggest no bridging instead of bridging (Grade 2C). In patients who require a dental procedure, we suggest continuing VKAs with an oral prohemostatic agent or stopping VKAs 2 to 3 days before the procedure instead of alternative strategies (Grade 2C). In moderate- to high-risk patients who are receiving acetylsalicylic acid (ASA) and require noncardiac surgery, we suggest continuing ASA around the time of surgery instead of stopping ASA 7 to 10 days before surgery (Grade 2C). In patients with a coronary stent who require surgery, we recommend deferring surgery > 6 weeks after bare-metal stent placement and > 6 months after drug-eluting stent placement instead of undertaking surgery within these time periods (Grade 1C); in patients requiring surgery within 6 weeks of bare-metal stent placement or within 6 months of drug-eluting stent placement, we suggest continuing antiplatelet therapy perioperatively instead of stopping therapy 7 to 10 days before surgery (Grade 2C). CONCLUSIONS Perioperative antithrombotic management is based on risk assessment for thromboembolism and bleeding, and recommended approaches aim to simplify patient management and minimize adverse clinical outcomes.

Can Patients Be Anticoagulated After Intracerebral Hemorrhage?: A Decision Analysis

Background and Purpose— Warfarin increases both the likelihood and the mortality of intracerebral hemorrhage (ICH), particularly in patients with a history of prior ICH. In light of this consideration, should a patient with both a history of ICH and a clear indication for anticoagulation such as nonvalvular atrial fibrillation be anticoagulated? In the absence of data from a clinical trial, we used a decision-analysis model to compare the expected values of 2 treatment strategies—warfarin and no anticoagulation—for such patients. Methods— We used a Markov state transition decision model stratified by location of hemorrhage (lobar or deep hemispheric). Effectiveness was measured in quality-adjusted life years (QALYs). Data sources included English language literature identified through MEDLINE searches and bibliographies from selected articles, along with empirical data from our own institution. The base case focused on a 69-year-old man with a history of ICH and newly diagnosed nonvalvular atrial fibrillation. Results— For patients with prior lobar ICH, withholding anticoagulation therapy was strongly preferred, improving quality-adjusted life expectancy by 1.9 QALYs. For patients with prior deep hemispheric ICH, withholding anticoagulation resulted in a smaller gain of 0.3 QALYs. In sensitivity analyses for patients with deep ICH, anticoagulation could be preferred if the risk of thromboembolic stroke is particularly high. Conclusions— Survivors of lobar ICH with atrial fibrillation should not be offered long-term anticoagulation. Similarly, most patients with deep hemispheric ICH and atrial fibrillation should not receive anticoagulant therapy. However, patients with deep hemispheric ICH at particularly high risk for thromboembolic stroke or low risk of ICH recurrence might benefit from long-term anticoagulation.

Moving the Tipping Point: The Decision to Anticoagulate Patients with Atrial Fibrillation

Background— The rate of ischemic stroke associated with traditional risk factors for patients with atrial fibrillation has declined over the past 2 decades. Furthermore, new and potentially safer anticoagulants are on the horizon. Thus, the balance between risk factors for stroke and benefit of anticoagulation may be shifting. Methods and Results— The Markov state transition decision model was used to analyze the CHADS2 score, above which anticoagulation is preferred, first using the stroke rate predicted for the CHADS2 derivation cohort, and then using the stroke rate from the more contemporary AnTicoagulation and Risk Factors In Atrial Fibrillation cohort for any CHADS2 score. The base case was a 69-year-old man with atrial fibrillation. Interventions included oral anticoagulant therapy with warfarin or a hypothetical “new and safer” anticoagulant (based on dabigatran), no antithrombotic therapy, or aspirin. Warfarin is preferred above a stroke rate of 1.7% per year, whereas aspirin is preferred at lower rates of stroke. Anticoagulation with warfarin is preferred even for a score of 0 using the higher rates of the older CHADS2 derivation cohort. Using more contemporary and lower estimates of stroke risk raises the threshold for use of warfarin to a CHADS2 score ≥2. However, anticoagulation with a “new, safer” agent, modeled on the results of the Randomized Evaluation of Long-Term Anticoagulation Therapy trial of dabigatran, leads to a lowering of the threshold for anticoagulation to a stroke rate of 0.9% per year. Conclusions— Use of a more contemporary estimate of stroke risk shifts the “tipping point,” such that anticoagulation is preferred at a higher CHADS2 score, reducing the number of patients for whom anticoagulation is recommended. The introduction of “new, safer” agents, however, would shift the tipping point in the opposite direction.

Methodology for the Development of Antithrombotic Therapy and Prevention of Thrombosis Guidelines: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines

BACKGROUND To develop the Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: ACCP Evidence-Based Clinical Practice Guidelines (AT9), the American College of Chest Physicians (ACCP) assembled a panel of clinical experts, information scientists, decision scientists, and systematic review and guideline methodologists. METHODS Clinical areas were designated as articles, and a methodologist without important intellectual or financial conflicts of interest led a panel for each article. Only panel members without significant conflicts of interest participated in making recommendations. Panelists specified the population, intervention and alternative, and outcomes for each clinical question and defined criteria for eligible studies. Panelists and an independent evidence-based practice center executed systematic searches for relevant studies and evaluated the evidence, and where resources and evidence permitted, they created standardized tables that present the quality of the evidence and key results in a transparent fashion. RESULTS One or more recommendations relate to each specific clinical question, and each recommendation is clearly linked to the underlying body of evidence. Judgments regarding the quality of evidence and strength of recommendations were based on approaches developed by the Grades of Recommendations, Assessment, Development, and Evaluation Working Group. Panel members constructed scenarios describing relevant health states and rated the disutility associated with these states based on an additional systematic review of evidence regarding patient values and preferences for antithrombotic therapy. These ratings guided value and preference decisions underlying the recommendations. Each topic panel identified questions in which resource allocation issues were particularly important and, for these issues, experts in economic analysis provided additional searches and guidance. CONCLUSIONS AT9 methodology reflects the current science of evidence-based clinical practice guideline development, with reliance on high-quality systematic reviews, a standardized process for quality assessment of individual studies and the body of evidence, an explicit process for translating the evidence into recommendations, disclosure of financial as well as intellectual conflicts of interest followed by management of disclosed conflicts, and extensive peer review.

The Cost-effectiveness of Screening for Chronic Hepatitis B Infection in the United States

BACKGROUND Hepatitis C virus (HCV) is the most common chronic blood-borne infection in the United States and will become an increasing source of morbidity and mortality with aging of the infected population. Our objective was to develop decision analytic models to explore the cost-effectiveness of screening in populations with varying prevalence of HCV and risks for fibrosis progression. METHODS We developed a Markov state transition model to examine screening of an asymptomatic community-based population in the United States. The base case was an ethnically and gender-mixed adult population with no prior knowledge of HCV status. Interventions were screening followed by guideline-based treatment, or no screening. Effectiveness was measured in quality-adjusted life-years (QALYs), and costs were measured in 2011 US dollars. RESULTS In the base case (US population, 49% male, 78% white, 13% African American, and 9% Hispanic, mean age, 46 years), screening followed by guideline-based treatment (using boceprevir as the direct-acting antiviral agent) of those with chronic HCV infection costs

Screening for the risk for bleeding or thrombosis.

47 276 per QALY. The overall HCV prevalence in the United States is reported to be 1.3%-1.9%, but prevalence varies markedly among patients with different numbers and types of risk factors. The marginal cost-effectiveness ratio (mCER) of screening decreases as prevalence increases. Below a prevalence of 0.84%, the mCER is greater than the generally accepted societal willingness-to-pay threshold of

Statin Use Following Intracerebral Hemorrhage: A Decision Analysis

50 000 per QALY and thus is not considered highly cost-effective. CONCLUSIONS Targeted screening is cost-effective when prevalence of HCV exceeds 0.84%. Prospective evaluation of a screening tool is warranted and should include comparisons with other screening strategies.

Cost-effectiveness of Interferon Gamma Release Assays vs Tuberculin Skin Tests in Health Care Workers

In this article, we review the laboratory tests used to screen patients for bleeding or thrombosis, their sensitivity and specificity, prevalence of bleeding disorders or thrombophilia in several clinical settings, and studies evaluating the clinical utility and economic effects of such testing. We add to past reviews on this topic by updating the literature review and by examining the utility of testing from a Bayesian perspective, using concepts of pretest probabilities, likelihood ratios, and post-test probabilities (for example, positive predictive value and negative predictive value). Screening for the Risk for Bleeding Screening tests include the readily available prothrombin time (PT), partial thromboplastin time (PTT), platelet estimate or count, and template bleeding time. All but the template bleeding time are highly reproducible, automated, and inexpensive on an individual basis but are expensive in the aggregate when routinely used to screen an unselected population (1). Obtaining a detailed history is the most important first step in determining whether testing is warranted (2). Nonsurgical Hospitalized Patients PT and PTT Patients hospitalized for nonsurgical diagnoses do not benefit from routine admission testing of PT or PTT when no evidence of synthetic liver dysfunction or history of oral anticoagulant use exists (3-6). Although randomized trials have not been done to assess the outcomes of hospitalized nonsurgical patients for whom coagulation testing was withheld, observational studies investigating the utility of these tests have failed to show improvement in clinical outcomes (5, 7, 8). Routine admission testing increases both expense and likelihood of false-positive results, leading to unnecessary additional testing. In 1979, Robbins and Rose (6) retrospectively analyzed abnormal results obtained from more than 1000 PTT measurements. Approximately 14% (143 patients) of the values were prolonged; however, 82% of the patients had known risk factors for bleeding (for example, known history of hemophilia, oral anticoagulant use, or history of liver disease). More important, the test did not alter clinical management for any of the patients. In a study of patients admitted to a Veterans Administration medical service for liver disease and bleeding disorders, Eisenberg and Goldfarb (4) found that PT contributed little to information already obtained from the history and physical examination. Only 2 of 107 patients who had a PT screening test had abnormal results, whereas 41 of 121 patients who had a pertinent history or physical examination had prolonged PTs. Erban and colleagues (9) evaluated ordering patterns and clinical indications for PT and PTT in 375 patients admitted to the medical service at the University of Pennsylvania, Philadelphia, Pennsylvania. Eighty-one percent of patients had PT and PTT ordered. When the appropriateness of test ordering compared with guidelines developed by the Medical Necessity Project of the Blue Cross and Blue Shield Associations of America (5) was evaluated, at least 70% of testing was not clinically indicated. They also found that test results had little impact on clinical care. Using 1988 U.S. dollars, they estimated that the direct cost per year attributable to inappropriate ordering of PTs and PTTs was more than

Effect of Laboratory Variation in the Prothrombin-Time Ratio on the Results of Oral Anticoagulant Therapy

60 000 at their institution alone. Although many physicians consider these tests to be inexpensive, small-ticket items, overuse in the aggregate can generate substantial unnecessary medical costs. Platelet Count The performance of routine platelet counts in asymptomatic nonsurgical patients also is not indicated and proves to be expensive. As shown by Robbins and Mushlin in 1979 (3), costs were more than