Treatment Of Symptomatic Pulmonary Embolism Research Articles

Rivaroxaban and Adjusted-Dose Warfarin Based on VKORC1 and CYP2C9 Genotypes for the Treatment of Symptomatic Pulmonary Embolism in Real World

SESSION TITLE: Pulmonary Vascular Disease: VTE SESSION TYPE: Original Investigation Poster PRESENTED ON: Saturday, April 16, 2016 at 11:45 AM - 12:45 PM PURPOSE: To compare the efficacy and safety of rivaroxaban and warfarin in treatment of pulmonary embolism (PE) and evaluate the clinical significance of the genotypes of VKORC1 and CYP2C9 in adjusted dose warfarin. METHODS: A total of 62 patients who had acute symptomatic PE with or without deep vein thrombosis (DVT) were randomized to receive rivaroxaban (n=30) (15 mg twice daily for 3 weeks, followed by 20 mg once daily last for the third months, then 10mg daily continued to the sixth months) or standard therapy of enoxaparin overlapping with and followed by an adjusted-dose warfarin (n=32) for 3 or 6 months. Meanwhile, the patients who receive warfarin were detected the genotypes of VKORC1 and CYP2C9. The primary efficacy outcome was recurrence and vanishing absorption of PE from imaging examination at the first month, third or sixth months. The principal safety outcome was major or non-major clinically relevant bleeding and other adverse events. RESULTS: There were no significant difference of primary efficacy outcome between rivaroxaban and standard therapy, whether at the first month (X2=2.848 P=0.416) or third and sixth months (X2=3.263 P=0.353). However, the length of hospital stay, rivaroxaban (9.29±3.70) was significantly less than standard therapy (11.38±3.12) (t=2.37 P=0.021). The non-major clinically relevant bleeding occurred in 5 (16.7%) patients in the rivaroxaban and in 16 (50%) patients in the standard therapy (t=7.681 P=0.006). Major bleeding was observed in no patients in rivaroxaban while in 2 (6.3%) patients in standard therapy. Other adverse events including 1 (3.3%) stroke in rivaroxaban and 1 (3.1%) death in standard therapy which all can not rule out PE. There were significant difference between the recommended dosages (3.5±0.86) of VKORC1 and CYP2C9 compared the actual dose of warfarin at discharge (4.02±1.26) (P=0.042). CONCLUSIONS: In patients with acute symptomatic PE, rivaroxaban was as efficacious as standard therapy enoxaparin followed by warfarin, However, the length of hospital stay, non-major clinically relevant and Major bleeding were significantly lower than standard therapy. Adjusting dose of warfarin which according toVKORC1 and CYP2C9, can not reduce the incidence of bleeding. CLINICAL IMPLICATIONS: Rivaroxaban has a similar efficacy while a better bleeding profile to standard therapy of enoxaparin overlapping with and followed by warfarin, and our study support the use of rivaroxaban as a single oral agent for patients with PE. Detecting VKORC1 and CYP2C9 maybe has little clinical significance. DISCLOSURE: The following authors have nothing to disclose: Linli Duan, Nuofu Zhang, Chunli Liu No Product/Research Disclosure Information

Oral rivaroxaban for the treatment of symptomatic pulmonary embolism: are we ready?

Can an oral regimen of rivaroxaban be used for the treatment of symptomatic pulmonary embolism? Büller H, Prins M, Lensing A, et al. Oral rivaroxaban for the treatment of symptomatic pulmonary embolism. N Engl J Med 2012;366:1287-97. To determine the effectiveness and safety of oral rivaroxaban in the treatment of symptomatic pulmonary embolism when compared to current standard therapy.

Apixaban was noninferior to enoxaparin plus warfarin in patients with acute venous thromboembolism

ACP Journal ClubOctober 15, 2013Apixaban was noninferior to enoxaparin plus warfarin in patients with acute venous thromboembolismThomas DeLoughery, MD, FACP, FAWMThomas DeLoughery, MD, FACP, FAWMOregon Health & Science University, Portland, Oregon, USA (T.D.)Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-159-8-201310150-02002 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail Source CitationAgnelli G, Buller HR, Cohen A, et al; Amplify Investigators. Oral apixaban for the treatment of acute venous thromboembolism. N Engl J Med. 2013;369:799-808. https://pubmed.ncbi.nlm.nih.gov/23808982Clinical Impact RatingsEmergency Med: Hematology: References1 Schulman S, Kearon C, Kakkar AK, et al; RE-COVER Study Group. Dabigatran versus warfarin in the treatment of acute venous thromboembolism. N Engl J Med. 2009;361:2342-52. [PMID: 19966341] Google Scholar2 EINSTEIN Investigators, Bauersachs R, Berkowitz SD, et al. Oral rivaroxaban for symptomatic venous thromboembolism. N Engl J Med. 2010;363:2499-510. [PMID: 21128814] Google Scholar3 EINSTEIN–PE Investigators, Büller HR, Prins MH, et al. Oral rivaroxaban for the treatment of symptomatic pulmonary embolism. N Engl J Med. 2012;366:1287-97. [PMID: 22449293] Google Scholar4 Lu G, DeGuzman FR, Hollenbach SJ, et al. A specific antidote for reversal of anticoagulation by direct and indirect inhibitors of coagulation factor Xa. Nat Med. 2013;19:446-51. [PMID: 23455714] Google Scholar Author, Article, and Disclosure InformationAffiliations: Oregon Health & Science University, Portland, Oregon, USA (T.D.) PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics October 15, 2013Volume 159, Issue 8Page: JC2 Issue Published: October 15, 2013 Copyright & PermissionsCopyright © 2013 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...

Outpatient treatment of symptomatic pulmonary embolism: A systematic review and meta-analysis

Patients with acute deep vein thrombus (DVT) can safely be treated as outpatients. However the role of outpatient treatment in patients diagnosed with a pulmonary embolism (PE) is controversial. We sought to determine the safety of outpatient management of patients with acute symptomatic PE. A systematic literature search strategy was conducted using MEDLINE, EMBASE, the Cochrane Register of Controlled Trials and all EBM Reviews. Pooled proportions for the different outcomes were calculated. A total of 1258 patients were included in the systematic review. The rate of recurrent venous thromboembolism (VTE) in patients with PE managed as outpatients was 1.47% (95% CI: 0.47 to 3.0%; I(2): 65.4%) during the 3 month follow-up period. The rate of fatal PE was 0.47% (95% CI: 0.16 to 1.0%; I(2): 0%). The rates of major bleeding and fatal intracranial hemorrhage were 0.81% (95% CI: 0.37 to 1.42%; I(2): 0%) and 0.29% (95% CI: 0.06 to 0.68%; I(2): 0%), respectively. The overall 3 month mortality rate was 1.58% (95% CI: 0.71 to 2.80%; I(2): 45%). The event rates were similar if employing risk stratification models versus using clinical gestalt to select appropriate patients for outpatient management. Independent of the risk stratification methods used, the rate of adverse events associated with outpatient PE treatment seems low. Based on our systematic review and pooled meta-analysis, low-risk patients with acute PE can safely be treated as outpatients if home circumstances are adequate.

New generation aspiration catheter: Feasibility in the treatment of pulmonary embolism

To report our preliminary experience with a new generation aspiration catheter in the treatment of symptomatic pulmonary embolism (PE). A retrospective database search for pulmonary artery embolectomy since introduction of the Pronto .035" and XL extraction catheter (Vascular Solutions, Minneapolis, MN) at our institution in 10/2009 was performed. Ten consecutive patients were identified in which the Pronto .035" or XL catheter was used between 01/2010 and 03/2013. All patients were referred for catheter based embolectomy due to contraindications to systemic lysis, or for being in such a critical clinical condition that immediate percutaneous treatment deemed warranted. The computed tomography (CT) right to left heart ratio as predictor for the severity of the PE was retrospectively evaluated on standard axial views. The difference between pre- and post-procedure pulmonary pressure measures was taken to assess the procedural effect. Extensive PE was confirmed angiographically in all patients. Measured right- to left ventricle (RV/LV) ratios were elevated beyond one in seven of the eight available CTs. Acute procedural success defined as clinical removal of visible thrombus and improvement in mean pulmonary artery pressure was seen in all recorded patients (n = 8), the mean pulmonary pressures declined from a median (range) of 35.5 (19-46) to 23 (10-37, P = 0.008) mmHg. Neither death nor other complications occurred intra- or immediately periprocedural, yet short term mortality within 30 d was found in 6 out of 9 patients, one patient was lost in follow up. The cause of death within 30 d in the 6 patients was identified as: Circulatory failure in direct connection with the PE (n = 2), stroke, sepsis, or succumbing to malignancy in a hospice setting (n = 2). Success in thrombus removal with improved pulmonary hypertension and systemic hypotension suggests this aspiration technique to be effective. Aspiration catheters should be part of further trials.

Outpatient Treatment of Symptomatic Pulmonary Embolism: A Systematic Review and Meta-Analysis

AbstractAbstract 361 Background:Patients with deep vein thrombus (DVT) can safely be treated as outpatients using subcutaneous low molecular weight heparin (LMWH). However the role of outpatient treatment in patients diagnosed with a pulmonary embolism (PE) is controversial. This practice is not accepted in many centers and majority of patients are still admitted to the hospital for observation. Clinicians are reluctant to discharge patients due to insufficient data supporting the safety of outpatient management of PE. Purpose:To determine the safety of outpatient treatment of acute symptomatic PE and the outcomes associated with outpatient management of PE including venous thromboembolism (VTE) recurrence, major bleeding, fatal PE, fatal intracranial hemorrhage (ICH), and overall mortality. Methods:A systematic literature search strategy was conducted using MEDLINE, EMBASE, the Cochrane Register of Controlled Trials and all EBM Reviews of published studies up to June 2012. We included randomized controlled trials (RCTs) and prospective cohort studies. We calculated the pooled proportions for the different outcomes at 3-months of follow-up. Ninety-five percent confidence intervals (95% CI) were calculated for each rate using the averaged, inverse variance-weighted estimates from each study. Results:Thirteen studies met all the inclusion criteria (3 RCTs and 10 prospective cohort studies). A total of 2458 patients were included in the systematic review. Different risk stratification methods were used to identify low risk patients with PE such as the pulmonary embolism severity index (PESI), the Geneva prognostic score, clinical gestalt and/or laboratory markers. The risk of recurrent VTE in patients with PE managed as outpatients was 1.64% (95% CI 0.69 – 3.0%; I2: 70.7%) during the 3 months follow-up period. The rate of fatal PE was 0.70% (95% CI 0.14 – 1. 7%; I2: 72.6%). The rates of major bleeding and ICH were 1.14% (95% CI 0.35 – 2.34%; I2: 72.8%) and 0.29% (95% CI 0.06– 0.68%; I2: 0%), respectively. The overall mortality rate was 2.3% (95% CI 0.41 – 5.7%; I-square: 92.8%). The I2 was moderate to high for most proportions, likely due to difference in the baseline characteristics (e.g. the inclusion of cancer patients in some studies). Conclusion:Independent of the risk stratification methods used, the rate of adverse events associated with outpatient PE treatment seems low. Based on our systematic review and pooled meta-analysis, numerous patients with acute PE can safely be treated as outpatients. [Display omitted] Proportion meta-analysis showing the risk of recurrent VTE in patients with PE managed as outpatients for a 3 month follow up period. Disclosures:No relevant conflicts of interest to declare.

Oral Rivaroxaban for the Treatment of Symptomatic Pulmonary Embolism

BackgroundA fixed-dose regimen of rivaroxaban, an oral factor Xa inhibitor, has been shown to be as effective as standard anticoagulant therapy for the treatment of deep-vein thrombosis, without the need for laboratory monitoring. This approach may also simplify the treatment of pulmonary embolism.MethodsIn a randomized, open-label, event-driven, noninferiority trial involving 4832 patients who had acute symptomatic pulmonary embolism with or without deep-vein thrombosis, we compared rivaroxaban (15 mg twice daily for 3 weeks, followed by 20 mg once daily) with standard therapy with enoxaparin followed by an adjusted-dose vitamin K antagonist for 3, 6, or 12 months. The primary efficacy outcome was symptomatic recurrent venous thromboembolism. The principal safety outcome was major or clinically relevant nonmajor bleeding.ResultsRivaroxaban was noninferior to standard therapy (noninferiority margin, 2.0; P=0.003) for the primary efficacy outcome, with 50 events in the rivaroxaban group (2.1%) versus 44 events in the standard-therapy group (1.8%) (hazard ratio, 1.12; 95% confidence interval [CI], 0.75 to 1.68). The principal safety outcome occurred in 10.3% of patients in the rivaroxaban group and 11.4% of those in the standard-therapy group (hazard ratio, 0.90; 95% CI, 0.76 to 1.07; P=0.23). Major bleeding was observed in 26 patients (1.1%) in the rivaroxaban group and 52 patients (2.2%) in the standard-therapy group (hazard ratio, 0.49; 95% CI, 0.31 to 0.79; P=0.003). Rates of other adverse events were similar in the two groups.ConclusionsA fixed-dose regimen of rivaroxaban alone was noninferior to standard therapy for the initial and long-term treatment of pulmonary embolism and had a potentially improved benefit–risk profile. (Funded by Bayer HealthCare and Janssen Pharmaceuticals; EINSTEIN-PE ClinicalTrials.gov number, NCT00439777.)

A Pilot Study of Computed Tomography–Detected Asymptomatic Pulmonary Filling Defects After Hip and Knee Arthroplasties

We asked what the incidence of asymptomatic filling defects is on routine multidetector computed tomography (MDCT) in primary hip (total hip arthroplasty [THA]) and knee arthroplasties (TKA) patients. We prospectively performed MDCT scans on the first postoperative day for THA (n = 21)/TKA (n = 27). Patients underwent routine postoperative care, and data were collected for symptoms such as tachycardia or shortness of breath. More patients undergoing TKA had positive computed tomography scans than those undergoing THA: 11 (41%) vs 1 (5%), respectively. All patients diagnosed with a filling defect were discharged from the hospital without treatment of symptomatic pulmonary embolism. Our study demonstrates a high rate of abnormal MDCT early after lower extremity arthroplasty, the clinical importance of which may be benign.

Outpatient treatment and early discharge of symptomatic pulmonary embolism: a systematic review

The published literature regarding the safety of outpatient treatment of symptomatic pulmonary embolism (PE) was systematically summarised. A literature search was performed using the PubMed and EMBASE databases. Studies in which patients had symptomatic PE and the antithrombotic treatment was administered completely at home or the patients were discharged early were selected. A scoring system was used to divide studies into three quality categories. Short- and long-term outcomes were extracted: all-cause mortality, death from PE or from major haemorrhage, recurrent venous thromboembolism, and major bleeding. Eleven observational studies were included. No randomised controlled studies were identified. No study fulfilled the criteria for high quality. A total of 928 patients with symptomatic PE were treated completely as outpatients or discharged early; haemodynamic instability and hypoxia were the main exclusion criteria. No patient died during the first 7 days of antithrombotic treatment. Outpatient treatment of symptomatic PE is not based on high-quality evidence. Although the published data suggest that certain subgroups of haemodynamically and respiratorily stable patients may be safely treated at home when a well-defined management programme is applied, further studies are warranted for a short-term prognostic risk stratification of this PE subgroup.

Treatment of early symptomatic pulmonary embolism after total joint arthroplasty

The purpose of this study was to evaluate the risk of intravenous heparin therapy or the use of Greenfield filters (Meditech, Watertown, MA) in the early postoperative period in patients who have documented symptomatic pulmonary embolism. Symptomatic pulmonary embolism in the first weeks was identified in 52 patients. Twenty-four patients were treated with Greenfield filter insertion and 28 patients with intravenous heparin therapy. One complication associated with insertion of the Greenfield filter—premature opening in the internal jugular vein—resulted in no adverse consequences. Three complications were associated with intravenous heparin therapy: one transient thrombocytopenia, one recurrent symptomatic pulmonary embolism, and one knee hematoma, which did not require surgical evacuation. It appears that Greenfield filter insertion is a viable option for treatment of symptomatic pulmonary embolism in the early postoperative period after total joint arthroplasty. In contrast to other published data, this study suggests that intravenous heparin therapy may also be a reasonable alternative, but is a treatment regimen that requires careful monitoring of platelets, wound complications, and bleeding parameters.