Idarucizumab for Dabigatran Reversal - Full Cohort Analysis.

BACKGROUND: Idarucizumab, a monoclonal antibody fragment, was developed to reverse the anticoagulant effect of dabigatran. METHODS: We performed a multicenter, prospective, open-label study to determine whether 5 g of intravenous idarucizumab would be able to reverse the anticoagulant effect of dabigatran in patients who had uncontrolled bleeding (group A) or were about to undergo an urgent procedure (group B). The primary end point was the maximum percentage reversal of the anticoagulant effect of dabigatran within 4 hours after the administration of idarucizumab, on the basis of the diluted thrombin time or ecarin clotting time. Secondary end points included the restoration of hemostasis and safety measures. RESULTS: A total of 503 patients were enrolled: 301 in group A, and 202 in group B. The median maximum percentage reversal of dabigatran was 100% (95% confidence interval, 100 to 100), on the basis of either the diluted thrombin time or the ecarin clotting time. In group A, 137 patients (45.5%) presented with gastrointestinal bleeding and 98 (32.6%) presented with intracranial hemorrhage; among the patients who could be assessed, the median time to the cessation of bleeding was 2.5 hours. In group B, the median time to the initiation of the intended procedure was 1.6 hours; periprocedural hemostasis was assessed as normal in 93.4% of the patients, mildly abnormal in 5.1%, and moderately abnormal in 1.5%. At 90 days, thrombotic events had occurred in 6.3% of the patients in group A and in 7.4% in group B, and the mortality rate was 18.8% and 18.9%, respectively. There were no serious adverse safety signals. CONCLUSIONS: In emergency situations, idarucizumab rapidly, durably, and safely reversed the anticoagulant effect of dabigatran. (Funded by Boehringer Ingelheim; RE-VERSE AD ClinicalTrials.gov number, NCT02104947 .)

The clinical effectiveness and cost-effectiveness of point-of-care tests (CoaguChek system, INRatio2 PT/INR monitor and ProTime Microcoagulation system) for the self-monitoring of the coagulation status of people receiving long-term vitamin K antagonist therapy, compared with standard UK practice : systematic review and economic evaluation

Funding The National Institute for Health Research Health Technology Assessment programme.Peer reviewedPublisher PD

Repeated Measurements of Cardiac Biomarkers in Atrial Fibrillation and Validation of the ABC Stroke Score Over Time

Background--Cardiac biomarkers are independent risk markers in atrial fibrillation, and the novel biomarker-based ABC stroke score (age, biomarkers, and clinical history of prior stroke) was recently shown to improve the prediction of stroke risk in patients with atrial fibrillation. Our aim was to investigate the short-term variability of the cardiac biomarkers and evaluate whether the ABC stroke risk score provides a stable short- term risk estimate. Methods and Results--According to the study protocol, samples were obtained at entry and also at 2 months in 4796 patients with atrial fibrillation followed for a median of 1.8 years in the ARISTOTLE (Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation) trial. Cardiac troponin I, cardiac troponin T, and N-terminal pro-B-type natriuretic peptide were measured with high-sensitivity immunoassays. Associations with outcomes were evaluated by Cox regression. C indices and calibration plots were used to evaluate the ABC stroke score at 2 months. The average changes in biomarker levels during 2 months were small ( median change cardiac troponin T +2.8%, troponin I +2.0%, and N-terminal pro-B-type natriuretic peptide +13.5%) and within-subject correlation was high ( all >= 0.82). Repeated measurement of cardiac biomarkers provided some incremental prognostic value for mortality but not for stroke when combined with clinical risk factors and baseline levels of the biomarkers. Based on 8702 person-years of follow-up and 96 stroke/systemic embolic events, the ABC stroke score at 2 months achieved a similar C index of 0.70 (95% CI, 0.65-0.76) as compared with 0.70 (95% CI, 0.65-0.75) at baseline. The ABC stroke score remained well calibrated using predefined risk classes. Conclusions--In patients with stable atrial fibrillation, the variability of the cardiac biomarkers and the biomarker- based ABC stroke score during 2 months are small. The prognostic information by the ABC stroke score remains consistent and well calibrated with similar good predictive performance if patients are retested after 2 months. Clinical Trial Registration --URL: http://www.clinicaltrials.gov. Unique identifier: NCT00412984.Peer reviewe

Early Adoption of Dabigatran and Its Dosing in US Patients With Atrial Fibrillation: Results From the Outcomes Registry for Better Informed Treatment of Atrial Fibrillation

Background: Dabigatran is a novel oral anticoagulant approved for thromboprophylaxis in atrial fibrillation. Adoption patterns of this new agent in community practice are unknown. Methods and Results: We studied patterns of dabigatran use among patients enrolled in the Outcomes Registry for Better Informed Treatment of Atrial Fibrillation (ORBIT‐AF) Registry between June 2010 and August 2011 and followed for 12 months. Among 9974 atrial fibrillation patients included, 1217 (12%) were treated with dabigatran during the study. Overall, patients receiving dabigatran were younger (median age 72 versus 75 years, P<0.0001), more likely to be white (92% versus 89%, P=0.005), more likely to have private insurance (33% versus 25%, P<0.0001), and less likely to have prior cardiovascular disease (4% versus 33%, P<0.0001). They had more new‐onset atrial fibrillation (8.8% versus 4.1%, P<0.0001), lower CHADS2 scores (estimated risk based on the presence of congestive heart failure, hypertension, aged ≥75 years, diabetes mellitus, and prior stroke or transient ischemic attack; mean 2.0 versus 2.3, P<0.0001), and lower Anticoagulation and Risk Factors in Atrial Fibrillation scores (mean 2.4 versus 2.8, P<0.0001). More than half (n=14/25, 56%) of patients with severe kidney disease were not prescribed reduced dosing, whereas 10% (n=91/920) with preserved renal function received lower dosing. Among patients not on dabigatran at baseline, 8% had dabigatran initiated during follow‐up. Patient education was significantly associated with switching from warfarin to dabigatran (adjusted odds ratio for postgraduate 1.73, P=0.007), whereas antiarrhythmic drug use significantly correlated with de novo adoption of dabigatran (adjusted odds ratio 2.4, P<0.0001). Conclusions: Patients receiving dabigatran were younger and at a lower risk of stroke and bleeding. Patients appeared to drive switching from warfarin, whereas clinical characteristics influenced de novo start of dabigatran. These data suggest cautious early uptake of dabigatran, and more careful attention to dosing adjustments is warranted. Clinical Trial Registration URL: Clinicaltrials.gov. Unique identifier: NCT01165710

Dental management considerations for the patient with an acquired coagulopathy. Part 1: Coagulopathies from systemic disease

Current teaching suggests that many patients are at risk for prolonged bleeding during and following invasive dental procedures, due to an acquired coagulopathy from systemic disease and/or from medications. However, treatment standards for these patients often are the result of long-standing dogma with little or no scientific basis. The medical history is critical for the identification of patients potentially at risk for prolonged bleeding from dental treatment. Some time-honoured laboratory tests have little or no use in community dental practice. Loss of functioning hepatic, renal, or bone marrow tissue predisposes to acquired coagulopathies through different mechanisms, but the relationship to oral haemostasis is poorly understood. Given the lack of established, science-based standards, proper dental management requires an understanding of certain principles of pathophysiology for these medical conditions and a few standard laboratory tests. Making changes in anticoagulant drug regimens are often unwarranted and/or expensive, and can put patients at far greater risk for morbidity and mortality than the unlikely outcome of postoperative bleeding. It should be recognised that prolonged bleeding is a rare event following invasive dental procedures, and therefore the vast majority of patients with suspected acquired coagulopathies are best managed in the community practice setting

Highlights from the III International Symposium of Thrombosis and Anticoagulation (ISTA), October 14-16, 2010, São Paulo, Brazil

To discuss and share knowledge around advances in the care of patients with thrombotic disorders, the Third International Symposium of Thrombosis and Anticoagulation was held in So Paulo, Brazil, from October 14-16, 2010. This scientific program was developed by clinicians for clinicians, and was promoted by four major clinical research institutes: the Brazilian Clinical Research Institute, the Duke Clinical Research Institute of the Duke University School of Medicine, the Canadian VIGOUR Centre, and the Uppsala Clinical Research Center. Comprising 3 days of academic presentations and open discussion, the symposium had as its primary goal to educate, motivate, and inspire internists, cardiologists, hematologists, and other physicians by convening national and international visionaries, thought-leaders, and dedicated clinician-scientists. This paper summarizes the symposium proceedings.AlexiumAstraZenecaBoehringer IngelheimBristol-Myers SquibbCSL BehringDaiichi SankyoLeo PharmaSanofi-aventisDuke Univ, Med Ctr, Duke Clin Res Inst, Durham, NC 27705 USAUniversidade Federal de São Paulo, Paulista Sch Med, São Paulo, BrazilUniv Alberta, Edmonton, AB, CanadaNatl Univ, Ctr Heart, Singapore, SingaporeMcMaster Univ, Hamilton, ON, CanadaBoston Univ, Boston, MA 02215 USAUppsala Univ, Uppsala, SwedenUniv Montreal, Montreal Heart Inst, Montreal, PQ, CanadaKatholieke Univ Leuven Hosp, Louvain, BelgiumGreen Lane Cardiovasc Res Unit, Auckland, New ZealandUniv São Paulo, Sch Med, São Paulo, BrazilFed Univ Hlth Sci Porto Alegre, Porto Alegre, RS, BrazilUniv Estadual Campinas, São Paulo, BrazilUniv New Mexico, Hlth Sci Ctr, Albuquerque, NM 87131 USAUniversidade Federal de São Paulo, Paulista Sch Med, São Paulo, BrazilWeb of Scienc

Prevalence and Predictors of Warfarin Use in Patients With Atrial Fibrillation at Low or Intermediate Risk and Relation to Thromboembolic Events

Background: According to the American College of Cardiology/American Heart Association/European Society of Cardiology guidelines, the choice of aspirin or warfarin to prevent thromboembolic events (TEs) in patients with nonrheumatic atrial fibrillation (AF) should be based on the CHADS 2 score. The purpose of this study was to determine the predictors of warfarin use in patients with AF at low (CHADS 2 =0) or intermediate (CHADS 2 =1) risk for TEs. Hypothesis: Warfarin use is low in intermediate‐ and low‐risk patients. Methods: Clinical characteristics of 3086 consecutive patients (mean age, 70 ± 13 years) with nonrheumatic AF from an academic multispecialty practice were determined between 2006 and 2008 through individual chart review. Patients were identified based on an inpatient or outpatient encounter, in which a billing diagnosis code of AF or atrial flutter (AFl) was recorded. The decision for anticoagulation was at the discretion of the primary care physician or cardiologist. No intervention to guide anticoagulant therapy was made. Results: Warfarin was prescribed in 180/497 low‐risk patients (36%), and in 646/938 intermediate‐risk patients (69%). Among high‐risk patients (CHADS 2 ≥2), warfarin was used in 792/968 patients (82%) with a CHADS 2 = 2, in 343/410 patients (84%) with a CHADS 2 =3, and in 225/273 patients (82%) with a CHADS 2 ≥4. On multivariate analysis, independent predictors of warfarin use in low‐risk patients were nonparoxysmal AF (odds ratio [OR]: 5.02, P< 0.0001) and age between 65 and 74 years (OR: 2.21, P< 0.0001). Among intermediate‐risk patients, congestive heart failure (OR: 7.34, P< 0.0001), nonparoxysmal AF (OR: 4.04, P< 0.0001), coronary artery disease (OR: 2.53, P< 0.0001), age between 65 and 74 years (OR: 1.68, P = 0.002), and female gender (OR: 1.69, P = 0.002) were independent predictors of warfarin use. Lack of warfarin use (OR: 4.9, P< 0.001) and female gender (OR: 2.0, P = 0.03) were associated with a higher risk of TEs in intermediate‐risk patients. None of the CHADS 2 parameters was predictive of TEs. Warfarin was not associated with reduction in TEs in low‐risk patients. Warfarin use did not have a significant effect on bleeding. Conclusions: Although either aspirin or warfarin is recommended to prevent TEs in patients with AF at intermediate risk for TEs, warfarin is preferred in the majority of patients in general practice. Lack of warfarin use is associated with a higher risk of TEs in intermediate‐risk patients with AF. The adoption of new oral anticoagulants that have lower risk of major hemorrhage than warfarin for low‐ or intermediate‐risk AF patients remains to be determined. © 2011 Wiley Periodicals, Inc. The authors have no funding, financial relationships, or conflicts of interest to disclose.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/86871/1/20967_ftp.pd

2017 HRS/EHRA/ECAS/APHRS/SOLAECE expert consensus statement on catheter and surgical ablation of atrial fibrillation: executive summary.

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2017 HRS/EHRA/ECAS/APHRS/SOLAECE expert consensus statement on catheter and surgical ablation of atrial fibrillation: executive summary.

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