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Association between rivaroxaban use and length of hospital stay, treatment costs and early outcomes in patients with pulmonary embolism: a systematic review of real-world studies.
Kohn, CG, Fermann, GJ, Peacock, WF, Wells, PS, Baugh, CW, Ashton, V, Crivera, C, Schein, JR, Wildgoose, P, Coleman, CI
Current medical research and opinion. 2017;(9):1697-1703
Abstract
BACKGROUND In the EINSTEIN-Pulmonary Embolism (PE) trial, subjects randomized to rivaroxaban versus enoxaparin bridging to vitamin K antagonist (VKA) therapy experienced a reduced index hospital length of stay (LOS). We sought to conduct a systematic review of real-world studies comparing LOS, costs and early outcomes among patients treated with rivaroxaban or parenterally bridged VKA in routine practice. METHODS We searched Medline and Scopus from 1 January 2011 to 30 November 2016 to identify observational studies comparing acute PE patients anticoagulated with rivaroxaban or parenterally bridged VKA and reporting data on index hospital LOS, costs and/or early post-PE outcomes. Studies not using appropriate methods for minimizing confounding bias or not published in English were excluded. RESULTS Five studies met inclusion criteria. Rivaroxaban use was associated with decreased index hospital LOS (range: 1.36-1.70 days) and treatment costs (range: $1818-$2688) during an index stay compared to parenterally bridged warfarin. No differences in early readmission for recurrent thrombosis were noted between anticoagulation strategies. Readmission for major bleeding was rare in both cohorts. Similar reductions in LOS (range: 0.23-4.3 days) and costs (range: $251-$7094) were observed with rivaroxaban in studies restricted to patients deemed low risk for early complications by clinical gestalt or by a clinical- or claims-based risk stratification tool. CONCLUSIONS Regardless of patient predicted risk of post-PE complications, real-world studies suggest that rivaroxaban is associated with a reduced hospital LOS and costs versus parenterally bridged warfarin, without increasing readmission.
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Effectiveness of Adaptive Statistical Iterative Reconstruction for 64-Slice Dual-Energy Computed Tomography Pulmonary Angiography in Patients With a Reduced Iodine Load: Comparison With Standard Computed Tomography Pulmonary Angiography.
Lee, JW, Lee, G, Lee, NK, Moon, JI, Ju, YH, Suh, YJ, Jeong, YJ
Journal of computer assisted tomography. 2016;(5):777-83
Abstract
OBJECTIVE The aim of the study was to assess the effectiveness of the adaptive statistical iterative reconstruction (ASIR) for dual-energy computed tomography pulmonary angiography (DE-CTPA) with a reduced iodine load. MATERIALS AND METHODS One hundred forty patients referred for chest CT were randomly divided into a DE-CTPA group with a reduced iodine load or a standard CTPA group. Quantitative and qualitative image qualities of virtual monochromatic spectral (VMS) images with filtered back projection (VMS-FBP) and those with 50% ASIR (VMS-ASIR) in the DE-CTPA group were compared. Image qualities of VMS-ASIR images in the DE-CTPA group and ASIR images in the standard CTPA group were also compared. RESULTS All quantitative and qualitative indices, except attenuation value of pulmonary artery in the VMS-ASIR subgroup, were superior to those in the VMS-FBP subgroup (all P < 0.001). Noise and signal-to-noise ratio of VMS-ASIR images were superior to those of ASIR images in the standard CTPA group (P < 0.001 and P = 0.007, respectively). Regarding qualitative indices, noise was significantly lower in VMS-ASIR images of the DE-CTPA group than in ASIR images of the standard CTPA group (P = 0.001). CONCLUSIONS The ASIR technique tends to improve the image quality of VMS imaging. Dual-energy computed tomography pulmonary angiography with ASIR can reduce contrast medium volume and produce images of comparable quality with those of standard CTPA.
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Safety and effectiveness of oral rivaroxaban versus standard anticoagulation for the treatment of symptomatic deep-vein thrombosis (XALIA): an international, prospective, non-interventional study.
Ageno, W, Mantovani, LG, Haas, S, Kreutz, R, Monje, D, Schneider, J, van Eickels, M, Gebel, M, Zell, E, Turpie, AG
The Lancet. Haematology. 2016;(1):e12-21
Abstract
BACKGROUND The efficacy and safety of the anticoagulant rivaroxaban for the treatment and secondary prevention of deep-vein thrombosis and pulmonary embolism has been shown in phase 3 trials. However, data about rivaroxaban use in routine clinical practice are needed. METHODS XA inhibition with rivaroxaban for Long-term and Initial Anticoagulation in venous thromboembolism (XALIA) was a multicentre, international, prospective, non-interventional study of patients with deep-vein thrombosis, done in hospitals and community care centres in 21 countries. The study investigated the safety and effectiveness of rivaroxaban compared with standard anticoagulation therapy (initial treatment with unfractionated heparin, low-molecular-weight heparin, or fondaparinux, usually overlapping with and followed by a vitamin K antagonist) for at least 3 months. Eligible patients were adults (aged ≥18 years) with an objectively confirmed diagnosis of deep-vein thrombosis, and an indication to receive anticoagulation treatment for at least 3 months. Following approval of rivaroxaban for the pulmonary embolism indication, patients with deep-vein thrombosis and concomitant pulmonary embolism were also eligible; however, those with isolated pulmonary embolism were not included. Type, dose, and duration of therapy for each patient were at the physician's discretion. The primary effectiveness and safety outcomes were major bleeding, recurrent venous thromboembolism, and all-cause mortality. Propensity score-adjusted analyses were done to account for potential imbalances between groups. This study is registered with ClinicalTrials.gov, number NCT01619007. FINDINGS Between June 26, 2012, and March 31, 2014, 5142 patients were enrolled. The safety population (all patients who received at least one dose of the anticoagulant of interest) comprised 2619 patients in the rivaroxaban group and 2149 in the standard anticoagulant therapy group. Patients in the rivaroxaban group were younger and fewer had active cancer or concomitant pulmonary embolism than those in the standard anticoagulation group. In the propensity score-adjusted population, the frequency of major bleeding was 0·8% (19/2505) in the rivaroxaban group and 2·1% (43/2010) in the standard anticoagulation group, with a propensity score-adjusted hazard ratio (HR) of 0·77 (95% CI 0·40-1·50); p=0·44. The frequency of recurrent venous thromboembolism was 1·4% (36/2505) in the rivaroxaban group and 2·3% (47/2010) in the standard anticoagulation group (propensity score-adjusted HR 0·91 [95% CI 0·54-1·54], p=0·72). The all-cause mortality frequency was 0·4% (11/2505) in the rivaroxaban group and 3·4% (69/2010) in the standard anticoagulation group (propensity score-adjusted HR 0·51 [95% CI 0·24-1·07], p=0·074). The incidence of treatment-emergent adverse events in the safety population was similar between the two groups (944 [36·0%] of 2619 in the rivaroxaban group vs 805 [37·5%] of 2149 in the standard anticoagulation group). INTERPRETATION In routine clinical practice, rivaroxaban-treated patients had a lower risk profile at baseline than those treated with standard anticoagulation. Propensity score-adjusted results confirm that rivaroxaban is a safe and effective alternative to standard anticoagulation therapy in a broad range of patients. Rates of major bleeding and recurrent venous thromboembolism were low in rivaroxaban-treated patients and consistent with phase 3 findings. FUNDING Bayer HealthCare Pharmaceuticals and Janssen Research & Development, LLC.
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Six Months vs Extended Oral Anticoagulation After a First Episode of Pulmonary Embolism: The PADIS-PE Randomized Clinical Trial.
Couturaud, F, Sanchez, O, Pernod, G, Mismetti, P, Jego, P, Duhamel, E, Provost, K, dit Sollier, CB, Presles, E, Castellant, P, et al
JAMA. 2015;(1):31-40
Abstract
IMPORTANCE The optimal duration of anticoagulation after a first episode of unprovoked pulmonary embolism is uncertain. OBJECTIVES To determine the benefits and harms of an additional 18-month treatment with warfarin vs placebo, after an initial 6-month nonrandomized treatment period on a vitamin K antagonist. DESIGN, SETTING, AND PARTICIPANTS Randomized, double-blind trial (treatment period, 18 months; median follow-up, 24 months); 371 adult patients who had experienced a first episode of symptomatic unprovoked pulmonary embolism (ie, with no major risk factor for thrombosis) and had been treated initially for 6 uninterrupted months with a vitamin K antagonist were randomized and followed up between July 2007 and September 2014 in 14 French centers. INTERVENTIONS Warfarin or placebo for 18 months. MAIN OUTCOMES AND MEASURES The primary outcome was the composite of recurrent venous thromboembolism or major bleeding at 18 months after randomization. Secondary outcomes were the composite at 42 months (treatment period plus 24-month follow-up), as well as each component of the composite, and death unrelated to pulmonary embolism or major bleeding, at 18 and 42 months. RESULTS After randomization, 4 patients were lost to follow-up, all after month 18, and 1 withdrew due to an adverse event. During the 18-month treatment period, the primary outcome occurred in 6 of 184 patients (3.3%) in the warfarin group and in 25 of 187 (13.5%) in the placebo group (hazard ratio [HR], 0.22; 95% CI, 0.09-0.55; P = .001). Recurrent venous thromboembolism occurred in 3 patients in the warfarin group and 25 patients in the placebo group (HR, 0.15; 95% CI, 0.05-0.43); major bleeding occurred in 4 patients in the warfarin group and in 1 patient in the placebo group (HR, 3.96; 95% CI, 0.44 to 35.89). During the 42-month entire study period (including the study treatment and follow-up periods), the composite outcome occurred in 33 patients (20.8%) in the warfarin group and in 42 (24.0%) in the placebo group (HR, 0.75; 95% CI, 0.47-1.18). Rates of recurrent venous thromboembolism, major bleeding, and unrelated death did not differ between groups. CONCLUSIONS AND RELEVANCE Among patients with a first episode of unprovoked pulmonary embolism who received 6 months of anticoagulant treatment, an additional 18 months of treatment with warfarin reduced the composite outcome of recurrent venous thrombosis and major bleeding compared with placebo. However, benefit was not maintained after discontinuation of anticoagulation therapy. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00740883.
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Prospective randomised comparison of diagnostic confidence and image quality with normal-dose and low-dose CT pulmonary angiography at various body weights.
Szucs-Farkas, Z, Megyeri, B, Christe, A, Vock, P, Heverhagen, JT, Schindera, ST
European radiology. 2014;(8):1868-77
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Abstract
OBJECTIVES To find a threshold body weight (BW) below 100 kg above which computed tomography pulmonary angiography (CTPA) using reduced radiation and a reduced contrast material (CM) dose provides significantly impaired quality and diagnostic confidence compared with standard-dose CTPA. METHODS In this prospectively randomised study of 501 patients with suspected pulmonary embolism and BW <100 kg, 246 were allocated into the low-dose group (80 kVp, 75 ml CM) and 255 into the normal-dose group (100 kVp, 100 ml CM). Contrast-to-noise ratio (CNR) in the pulmonary trunk was calculated. Two blinded chest radiologists independently evaluated subjective image quality and diagnostic confidence. Data were compared between the normal-dose and low-dose groups in five BW subgroups. RESULTS Vessel attenuation did not differ between the normal-dose and low-dose groups within each BW subgroup (P = 1.0). The CNR was higher with the normal-dose compared with the low-dose protocol (P < 0.006) in all BW subgroups except for the 90-99 kg subgroup (P = 0.812). Subjective image quality and diagnostic confidence did not differ between CT protocols in all subgroups (P between 0.960 and 1.0). CONCLUSIONS Subjective image quality and diagnostic confidence with 80 kVp CTPA is not different from normal-dose protocol in any BW group up to 100 kg. KEY POINTS • 80 kVp CTPA is safe in patients weighing <100 kg • Reduced radiation and iodine dose still provide high vessel attenuation • Image quality and diagnostic confidence with low-dose CTPA is good • Diagnostic confidence does not deteriorate in obese patients weighing <100 kg.
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[Edoxaban is safer than vitamin K antagonists].
Einecke, D
MMW Fortschritte der Medizin. 2013;(16):20
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Clot resolution after 3 weeks of anticoagulant treatment for pulmonary embolism: comparison of computed tomography and perfusion scintigraphy.
van Es, J, Douma, RA, Kamphuisen, PW, Gerdes, VE, Verhamme, P, Wells, PS, Bounameaux, H, Lensing, AW, Büller, HR
Journal of thrombosis and haemostasis : JTH. 2013;(4):679-85
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INTRODUCTION Little is known about the natural history of clot resolution in the initial weeks of anticoagulant therapy in patients with acute pulmonary embolism (PE). Clot resolution of acute PE was assessed with either computed tomography pulmonary angiography scan (CT-scan) or perfusion scintigraphy scan (Q-scan) after 3 weeks of treatment. METHODS This was a predefined safety analysis of the Einstein PE study, including PE patients, randomized to either enoxaparin with vitamin K antagonist (VKA) or rivaroxaban. A similar scan as at baseline was repeated after 3 weeks. The percentage of vascular obstruction (PVO) was calculated on the basis of a weighted semiquantitative estimation of obstruction. Clot resolution was assessed blindly by calculating the relative change after 3 weeks. RESULTS PE was diagnosed in 264 patients with CT-scan and in 83 with Q-scan. Baseline characteristics were similar. At baseline, the mean PVO assessed with CT-scan (PVO-CT) and the mean PVO assessed with Q-scan (PVO-Q) were both 21% (standard deviation [SD] 13%) (P = 0.9). The mean relative decrease in PVO was 71% (SD 33%) for PVO-CT, and 62% (SD 36%) for PVO-Q (P = 0.02); complete resolution was observed in 44% (116/264; 95% confidence interval [CI] 38-50%) and 31% (26/83; 95% CI 22-42%) with CT-scan and Q-scan, respectively (P = 0.04). No difference in clot resolution between enoxaparin/VKA and rivaroxaban was found. CONCLUSION In patients with acute PE, only 3 weeks of anticoagulant treatment leads to complete clot resolution in a considerable proportion of patients, and normalization is more often observed with CT-scan than with Q-scan.
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Reduced iodine load at CT pulmonary angiography with dual-energy monochromatic imaging: comparison with standard CT pulmonary angiography--a prospective randomized trial.
Yuan, R, Shuman, WP, Earls, JP, Hague, CJ, Mumtaz, HA, Scott-Moncrieff, A, Ellis, JD, Mayo, JR, Leipsic, JA
Radiology. 2012;(1):290-7
Abstract
PURPOSE To compare quantitative and subjective image quality and radiation dose between standard computed tomographic (CT) pulmonary angiography (CTPA) and CTPA with a dual-energy technique with reduced iodine load. MATERIALS AND METHODS This prospective study was approved by the institutional review board and each participant provided informed consent. Ninety-four patients (59% male; mean age ± standard deviation, 62 years ± 15) were randomized to one of two protocols: standard CTPA (100-120 kVp) with standard contrast medium injection (n = 46) and dual-energy CTPA (image reconstruction at 50 keV) with the same injection volume as in the standard protocol but composed of contrast medium and saline in a 1:1 fashion, resulting in 50% reduction in iodine load (n = 48). Signal intensity and noise in three central and two segmental pulmonary arteries were measured; signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR) were calculated. A five-point scale was used to subjectively evaluate vascular enhancement and image noise. The proportion of diagnostic (score, ≥ 3) studies and the interreader agreement regarding the dichotomized diagnostic versus nondiagnostic scale were compared between the two groups. RESULTS Compared with standard CTPA, dual-energy CTPA demonstrated higher signal intensity in all pulmonary arteries (all P < .01), inferior noise only in segmental arteries (P < .05), higher SNR and CNR (both P < .05), and compatible effective dose (P > .05). The five-point score was higher in the standard CTPA protocol (P < .05). The interreader agreement regarding the dichotomized diagnostic versus nondiagnostic scale was similar (P > .05) between the two groups. CONCLUSION Dual-energy CTPA with image reconstruction at 50 keV allows a significant reduction in iodine load while improving intravascular signal intensity, maintaining SNR and with comparable radiation dose.
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Enoxaparin followed by once-weekly idrabiotaparinux versus enoxaparin plus warfarin for patients with acute symptomatic pulmonary embolism: a randomised, double-blind, double-dummy, non-inferiority trial.
Büller, HR, Gallus, AS, Pillion, G, Prins, MH, Raskob, GE, ,
Lancet (London, England). 2012;(9811):123-9
Abstract
BACKGROUND Treatment of pulmonary embolism with low-molecular-weight heparin and vitamin K antagonists, such as warfarin, is not ideal. We aimed to assess non-inferiority of idrabiotaparinux, a reversible longlasting indirect inhibitor of activated factor X, to warfarin in patients with acute symptomatic pulmonary embolism. METHODS In our randomised, double-blind, double-dummy, non-inferiority trial, we enrolled adults with objectively documented acute symptomatic pulmonary embolism attending 291 centres in 37 countries. We excluded patients who were pregnant, had active bleeding, kidney failure, or malignant hypertension, or were at high risk of death, bleeding, or adverse reactions to study drugs. We randomly allocated patients to receive 5-10 days' enoxaparin 1·0 mg/kg twice daily followed by subcutaneous idrabiotaparinux (starting dose 3·0 mg) or adjusted-dose warfarin (target international normalised ratio 2·0-3·0); regimens lasted 3 months or 6 months dependent on clinical presentation. Block randomisation was done with a central interactive computerised system, stratified by study centre and intended treatment duration. The primary efficacy outcome was recurrent venous thromboembolism at 99 days after randomisation. We estimated the odds ratio and 95% CI with a Mantel-Haenzsel χ(2) analysis (non-inferiority margin 2·0) in the intention-to-treat population. The main safety outcome was clinically relevant bleeding (major or non-major) in all patients at day 99. This study is registered with ClinicalTrials.gov, number NCT00345618. FINDINGS Between Aug 1, 2006, and Jan 31, 2010, we enrolled 3202 patients aged 18-96 years. 34 (2%) of 1599 patients randomly allocated to receive enoxaparin-idrabiotaparinux and 43 (3%) of 1603 patients randomly allocated to receive enoxaparin-warfarin had recurrent venous thromboembolism (odds ratio 0·79, 95% CI 0·50-1·25; p(non-inferiority)=0·0001). 72 (5%) of 1599 patients in the enoxaparin-idrabiotaparinux group and 106 (7%) of 1603 patients in the enoxaparin-warfarin group had clinically relevant bleeding (0·67, 0·49-0·91; p(superiority)=0·0098). We noted similar differences in outcomes in those patients treated to 6 months. INTERPRETATION Idrabiotaparinux could provide an attractive alternative to warfarin for the long-term treatment of pulmonary embolism, and seems to be associated with reduced bleeding. FUNDING Sanofi-Aventis (Paris, France).
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Comparison of the effect of low- and iso-osmolar contrast agents on heart rate during chest CT angiography: results of a prospective randomized multicenter study.
Chartrand-Lefebvre, C, White, CS, Bhalla, S, Mayo-Smith, WW, Prenovault, J, Vydareny, KH, Soto, JA, Ozkan, OS, Chughtai, AR, Soulez, G
Radiology. 2011;(3):930-7
Abstract
PURPOSE To prospectively compare the effect of intravenous injection of low-osmolar iopamidol with that of intravenous injection of iso-osmolar iodixanol on heart rate (HR) during nongated chest computed tomographic (CT) angiography. MATERIALS AND METHODS This multicenter study was approved by local institutional review boards, and patients provided written informed consent. Patient enrollment and examination at centers in the United States complied with HIPAA regulations. One hundred and thirty patients (54 male; mean age, 52 years) clinically suspected of having pulmonary embolism were referred for pulmonary CT angiography and were randomly assigned to receive 80 mL of either iopamidol (370 mg of iodine per milliliter, n = 63) or iodixanol (320 mg of iodine per milliliter, n = 67) at a rate of 4 mL/sec. HR (measured in beats per minute) was monitored from 5 minutes before the start of injection to the end of imaging, and precontrast HR and maximum postcontrast HR were recorded. Student t and χ(2) tests were used for continuous and categorical variables, respectively. RESULTS Precontrast HR in patients who received iopamidol (mean, 81 beats per minute ± 18 [standard deviation]) was similar to that in patients who received iodixanol (mean, 77 beats per minute ± 17) (P = .16). Mean postcontrast HR was 87 beats per minute ± 17 and 82 beats per minute ± 18 (P = .16) in the iopamidol and iodixanol groups, respectively. Mean increase from precontrast HR to postcontrast HR was 5 beats per minute ± 9 and 5 beats per minute ± 7 (P = .72) in the iopamidol and iodixanol groups, respectively. Thirty-five (56%) of the 63 patients who received iopamidol and 33 (49%) of the 67 patients who received iodixanol had an HR increase of fewer than 5 beats per minute, 15 (24%) and 18 (27%) patients, respectively, had an increase of 5-9 beats per minute, and four (6%) and three (4%) patients, respectively, had an increase of more than 20 beats per minute. These proportions were not significantly different between the groups (P = .51, χ(2) test). CONCLUSION High-rate intravenous administration of 80 mL of iopamidol and iodixanol during pulmonary CT angiography slightly increased HR; there was no difference in HR between the contrast agent groups.