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BACKGROUND: The use of direct oral anticoagulants (DOACs) as an alternative to low-molecular-weight heparin (LMWH) for extended thromboprophylaxis of abdominal/pelvic cancer-related postoperative thromboembolism (VTE) is unclear. We aim to investigate the efficacy and safety of DOACs vs. LMWH in these patients. METHODS: A systematic review was conducted using EMBASE, MEDLINE, CENTRAL, and Web of science through May 19th, 2023 for all randomized controlled trials (RCTs) and observational studies that compared the outcomes with DOACs vs. LMWH for extended thromboprophylaxis among patients undergoing abdominal/pelvic cancer surgery. Primary efficacy outcome was clinical VTE, and safety outcome was clinically relevant bleeding complications reported within the 30-day postoperative period. This study was registered in PROSPERO (CRD42023413175). RESULTS: We identified 5078 articles and selected 29 full-text articles for eligibility. A total of 9 studies (2 RCTs and 7 observational studies) encompassing 2651 patients were included for systematic review and 7 for meta-analysis. When compared with LMWH extended thromboprophylaxis, DOACs had a similar incidence of VTE (RR: 0.65 [95% CI: 0.32-1.33], I2 = 0%), major bleeding (RR: 1.68 [95% CI: 0.36-7.9], I2 = 26%), and clinically relevant non-major bleeding (RR: 0.68 [95% CI: 0.39-1.19], I2 = 0%). Subgroup analysis suggested no difference according to the study type (RCTs versus observational studies) regarding clinical VTE or major bleeding (Pinteraction = 0.43 and Pinteraction = 0.71, respectively). CONCLUSION: Our results suggest that DOACs for extended thromboprophylaxis were an effective and safe alternative to LMWH after major abdominal/pelvic cancer-related surgery.
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Anticoagulantes , Heparina de Bajo-Peso-Molecular , Neoplasias Pélvicas , Complicaciones Posoperatorias , Tromboembolia Venosa , Humanos , Heparina de Bajo-Peso-Molecular/uso terapéutico , Heparina de Bajo-Peso-Molecular/administración & dosificación , Tromboembolia Venosa/prevención & control , Tromboembolia Venosa/etiología , Anticoagulantes/administración & dosificación , Anticoagulantes/uso terapéutico , Complicaciones Posoperatorias/prevención & control , Neoplasias Pélvicas/cirugía , Administración Oral , Neoplasias Abdominales/cirugíaRESUMEN
BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) is associated with increased venous thromboembolism (VTE). We sought to compare rates of bleeding complications and VTE in patients receiving extended postoperative thromboprophylaxis (EPT) to those who did not, and identify risk factors for VTE after pancreatectomy for PDAC. METHODS: This is a retrospective review of pancreatectomies for PDAC. EPT was defined as 28 days of low molecular weight heparin. Multivariable analysis (MVA) was performed to identify independent risk factors of VTE. RESULTS: Of 269 patients included, 142 (52.8%) received EPT. Of those who received EPT, 7 (4.9%) suffered bleeding complications, compared to 6 (4.7%) of those who did not (p = 0.938). There was no significant difference in VTE rate at 90 days (2.8% vs. 2.4%, p = 0.728) or at 1 year (6.3% vs. 7.9%, p = 0.624). On MVA, risk factors for VTE included worse performance status, lower preoperative hematocrit, R1/R2 resection, and minimally invasive (MIS) approach. Among those who received EPT, there was no difference in VTE rate between MIS and open approach. CONCLUSIONS: EPT was not associated with a difference in VTE risk or bleeding complications. MIS approach was associated with a higher risk of VTE; however, this was significantly lower among those who received EPT.
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Carcinoma Ductal Pancreático , Neoplasias Pancreáticas , Tromboembolia Venosa , Humanos , Anticoagulantes/uso terapéutico , Tromboembolia Venosa/etiología , Tromboembolia Venosa/prevención & control , Pancreatectomía/efectos adversos , Heparina de Bajo-Peso-Molecular/uso terapéutico , Neoplasias Pancreáticas/cirugía , Neoplasias Pancreáticas/complicaciones , Factores de Riesgo , Carcinoma Ductal Pancreático/cirugía , Complicaciones Posoperatorias/etiología , Complicaciones Posoperatorias/prevención & control , Neoplasias PancreáticasRESUMEN
BACKGROUND: The effect of extended thromboprophylaxis in improving the prognosis of adult patients with coronavirus disease 2019 (COVID-19) after discharge remains debatable. This meta-analysis was aimed to determine the advantages and disadvantages of extended thromboprophylaxis in these patients. METHODS: Different databases such as PubMed, Embase, Web of Science, and Cochrane Library were systematically searched for studies that evaluated the effects of extended thromboprophylaxis in post-discharge patients with COVID-19 until 13 June 2022. The primary efficacy outcome was defined by the composite outcome of thromboembolism and all-cause mortality, and the safety outcome was defined by bleeding events. The odds ratios (ORs) and 95 % confidence intervals (CIs) of efficacy and safety outcomes were calculated using fixed- or random-effects model. Interaction analysis was performed to assess and compare observational studies and randomised controlled trials (RCTs). A sensitivity analysis was performed after excluding studies of poor quality. RESULTS: Eight studies involving 10,148 patients were included. The results confirmed that extended thromboprophylaxis, primarily prophylactic use of anticoagulants for <35 days, was significantly associated with reduced composite outcome in high-risk post-discharge patients with COVID-19 (OR: 0.52; 95 % CI: 0.41-0.67, P = 0.000). Interaction analysis revealed that the effect estimates were consistent between the RCT and observational studies (Pinteraction = 0.310). Furthermore, extended thromboprophylaxis did not increase the risk of major bleeding events (OR: 1.64; 95 % CI: 0.95-2.82, P = 0.075). CONCLUSION: In post-discharge patients with COVID-19 at high risk of thromboembolism, extended thromboprophylaxis, primarily prophylactic use of anticoagulants for <35 days, can significantly reduce the risk of thrombosis and all-cause mortality without increasing the risk of major bleeding events. REGISTRATION: PROSPERO CRD42022339399.
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COVID-19 , Tromboembolia Venosa , Adulto , Humanos , Alta del Paciente , Tromboembolia Venosa/etiología , Tromboembolia Venosa/prevención & control , Tromboembolia Venosa/tratamiento farmacológico , COVID-19/complicaciones , Anticoagulantes/efectos adversos , Hemorragia/inducido químicamente , Hemorragia/tratamiento farmacológicoRESUMEN
INTRODUCTION: Hospitalized COVID-19 patients, particularly those with high-risk features, are at risk for venous and arterial thromboembolic events for approximately 30 days or more after hospital discharge. Extended post-hospital discharge thromboprophylaxis has potential to reduce this risk. AREAS COVERED: Recent cohort, registry, and randomized trial data on the topic of extended post-discharge thromboprophylaxis in COVID-19 inpatients are reviewed, and key patient subgroups at high thrombotic risk are highlighted, with antithrombotic guidelines on the topic discussed. EXPERT OPINION: COVID-19 inpatients with cardiovascular risk factors, advanced age, intensive care unit stay, or an IMPROVE VTE score of 4 or more or a score of 2 or 3 plus elevated D-dimers (> twice the upper limit of normal) or an IMPROVE-DD VTE score of ≥4 are at high thrombotic risk in the post-discharge period. These high-risk patient subgroups benefit from extended post-discharge thromboprophylaxis, specifically with rivaroxaban 10 mg daily for 35 days. Recent NIH and ISTH guidelines recommend or suggest this approach. Results from other clinical trials are pending.
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COVID-19 , Tromboembolia Venosa , Cuidados Posteriores , Anticoagulantes/uso terapéutico , COVID-19/complicaciones , Humanos , Alta del Paciente , Ensayos Clínicos Controlados Aleatorios como Asunto , Tromboembolia Venosa/tratamiento farmacológico , Tromboembolia Venosa/etiología , Tromboembolia Venosa/prevención & controlRESUMEN
Background Readmission occurs in 1 out of 3 patients with heart failure (HF). We aimed to study the incidence and prognostic implications of rehospitalizations because of arterial thromboembolism events (ATEs) and venous thromboembolism events (VTEs) after discharge in patients with HF. Methods and Results We identified Medicare beneficiaries who were admitted with a primary diagnosis of HF from 2014 to 2019, with a hospital stay ranging between 3 and10 days, followed by discharge to home. We calculated incidence of ATEs (myocardial infarction, ischemic stroke, or systemic embolism) and VTEs (deep venous thrombosis and pulmonary embolism) up to 90 days after discharge. Out of 2 953 299 patients admitted with HF during the study period, a total of 585 353 patients met the inclusion criteria, and 36.6% were readmitted within 90 days of discharge. The incidence of readmission due ATEs, VTEs, HF, and all other reasons was 3.4%, 0.5%, 13.2%, and 19.5%, respectively. Incidence of thromboembolic events was highest within 14 days after discharge. Factors associated with ATEs included prior coronary, peripheral, or cerebrovascular disease and for VTEs included malignancy and prior liver or lung disease. ATE/VTE readmission had a 30-day mortality of 19.9%. After a median follow-up period of 25.6 months, ATE and VTE readmissions were associated with higher risk of mortality (hazard ratio, 2.76 [95% CI, 2.71-2.81] and 2.17 [95% CI, 2.08-2.27], respectively; P<0.001 for both) compared with no readmission on time-dependent Cox regression. Conclusions After a HF hospitalization, 3.9% of patients were readmitted with a thromboembolic event that was associated with 2- to 3-fold greater risk of mortality in follow-up.
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Insuficiencia Cardíaca , Trombosis , Tromboembolia Venosa , Anciano , Insuficiencia Cardíaca/complicaciones , Insuficiencia Cardíaca/epidemiología , Insuficiencia Cardíaca/terapia , Hospitalización , Humanos , Incidencia , Medicare , Readmisión del Paciente , Pronóstico , Estudios Retrospectivos , Factores de Riesgo , Trombosis/complicaciones , Estados Unidos/epidemiología , Tromboembolia Venosa/diagnóstico , Tromboembolia Venosa/epidemiología , Tromboembolia Venosa/etiologíaRESUMEN
Extended thromboprophylaxis given to medically ill patients for up to 45 days following an acute hospitalization remains an emerging topic among many hospital-based health care providers. Recent advancements in the field of extended thromboprophylaxis using risk stratification and careful patient selection criteria have led to an improved safety profile of direct oral anticoagulants (DOACs) and established net clinical benefit when given to key patient subgroups at high risk of venous thromboembolism (VTE) and low risk of bleeding. The Food and Drug Administration (FDA) has now approved the DOACs betrixaban and rivaroxaban for both in-hospital and extended thromboprophylaxis in medically ill patients in these key subgroups, which represents more than one-quarter of hospitalized medically ill patients. This has potential to significantly reduce VTE-related morbidity and mortality for these patients. Emerging data also supports reductions in the risk of arterial thromboembolism in medically ill patients with extended thromboprophylaxis post-hospital discharge using DOACs. This article aims to review the most recent concepts of predicting and preventing VTE and to discuss emerging paradigms of extended thromboprophylaxis in hospitalized medically ill patients utilizing an individualized, risk-adapted approach.
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An individualized approach to identify acutely ill medical patients at increased risk of venous thromboembolism (VTE) and a low risk of bleeding to optimize the benefit and risk of extended thromboprophylaxis (ET) is needed. The International Medical Prevention Registry on Venous Thromboembolism (IMPROVE) VTE risk score has undergone extensive external validation in medically ill patients for in-hospital use and a modified model was used in the MARINER trial of ET also incorporating an elevated D-dimer. The MAGELLAN study demonstrated efficacy with rivaroxaban but had excess bleeding. This retrospective analysis investigated whether the modified IMPROVE VTE model with an elevated D-dimer could identify a high VTE risk subgroup of patients for ET from a subpopulation of the MAGELLAN study, which was previously identified as having a lower risk of bleeding. We incorporated the modified IMPROVE VTE score using a cutoff score of 4 or more or 2 and 3 with an elevated D-dimer (>2 times the upper limit of normal) to the MAGELLAN subpopulation. In total, 56% of the patients met the high-risk criteria. In the placebo group, the total VTE event rate at Day 35 was 7.94% in the high-risk group and 2.83% for patients in the lower-risk group. A reduction in VTE was observed with rivaroxaban in the high-risk group (relative risk [RR]: 0.68, 95% confidence interval [CI]: 0.51-0.91, p = 0.008) and in the lower-risk group (RR: 0.69, 95% CI: 0.40 -1.20, p = 0.187). The modified IMPROVE VTE score with an elevated D-dimer identified a nearly threefold higher VTE risk subpopulation of patients where a significant benefit exists for ET using rivaroxaban.
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Major medical illnesses place patients at risk of venous thromboembolism (VTE). Some risk factors including age ≥75 years or history of cancer place them at increased risk of VTE that extends for at least 5 to 6 weeks following hospital admission. Betrixaban thromboprophylaxis is now approved in the United States for this indication. We estimated the annual number of acutely ill medical patients at extended risk of VTE discharged from US hospital. Major medical illnesses (stroke, respiratory failure/chronic obstructive pulmonary disease, heart failure, pneumonia, other infections, and rheumatologic disorders) and 2 common risk factors for extended VTE risk, namely, age ≥75 years and history of cancer (active or past) were examined in 2014 US hospital discharges using the first 3 discharge diagnosis codes in the National Inpatient Sample (database of acute-care hospital discharges from the US Agency for Health Care Quality and Research). In 2014, there were 20.8 million discharges with potentially at risk of nonsurgical-related VTE. Overall, 7.2 million (35%) discharges corresponded to major medical illness that warranted thromboprophylaxis according to 2012 American College of Chest Physicians (ACCP) guideline. Among them, 2.79 million were aged ≥75 years and 1.36 million had a history of cancer (aged 40-74 years). Overall, 3.48 million discharges were at extended risk of VTE. Many medical inpatients at risk of VTE according to 2012 ACCP guideline might benefit from the awareness of continuing risk and some of these patients might benefit from extended thromboprophylaxis, depending on the risk of bleeding and comorbidities.
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Alta del Paciente , Premedicación/métodos , Medición de Riesgo , Tromboembolia Venosa/prevención & control , Adulto , Anciano , Comorbilidad , Femenino , Adhesión a Directriz , Hemorragia , Hospitalización , Humanos , Masculino , Persona de Mediana Edad , Estados Unidos , Tromboembolia Venosa/tratamiento farmacológicoRESUMEN
OBJECTIVES: Venous thromboembolism (VTE), consisting of both pulmonary embolism (PE) and deep vein thromboses (DVT), remains a well-recognised complication of major urological cancer surgery. Several international guidelines recommend extended thromboprophylaxis (ETP) with LMWH, whereby the period of delivery is extended to the post-discharge period, where the majority of VTE occurs. In this literature review we investigate whether ETP should be indicated for all patients undergoing major urological cancer surgery, as well procedure specific data that may influence a clinician's decision. METHODS: We performed a search of six databases (PubMed, Cochrane, EMBASE, Cumulative Index to Nursing and Allied Health Literature (CINAHL), PsycINFO, and British Nursing Index (BNI)) from inception to June 2019, for studies looking at adult patients who received VTE prophylaxis after surgery for a major urological malignancy. RESULTS: Eighteen studies were analysed. VTE risk is highest in open and robotic Radical Cystectomy (RC) (2.6-11.6%) and ETP demonstrates a significant reduction in risk of VTE, but not a significant difference in Pulmonary Embolism (PE) or mortality. Risk of VTE in open Radical Prostatectomy (RP) (0.8-15.7%) is comparable to RC, but robotic RP (0.2-0.9%), open partial/radical nephrectomy (1.0-4.4%) and robotic partial/radical nephrectomy (0.7-3.9%) were lower risk. It has not been shown that ETP reduces VTE risk specifically for RP or nephrectomy. CONCLUSION: The decision to use ETP is a fine balance between variables such as VTE incidence, bleeding risk and perioperative morbidity/mortality. This balance should be assessed for each specific procedure type. While ETP still remains of net benefit for open RP as well as open and robotic RC, the balance is closer for minimally invasive RP as well as radical and partial nephrectomy. Due to a lack of procedure specific evidence for the use of ETP, adherence with national guidelines remains poor. Therefore, we advocate further studies directly comparing ETP vs standard prophylaxis, for specific procedure types, in order to allow clinicians to make a more informed decision in future.
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Anticoagulantes , Procedimientos Quirúrgicos Urológicos , Tromboembolia Venosa , Anticoagulantes/administración & dosificación , Anticoagulantes/efectos adversos , Anticoagulantes/uso terapéutico , Humanos , Neoplasias Urológicas/cirugía , Procedimientos Quirúrgicos Urológicos/efectos adversos , Procedimientos Quirúrgicos Urológicos/estadística & datos numéricos , Tromboembolia Venosa/epidemiología , Tromboembolia Venosa/prevención & controlRESUMEN
BACKGROUND: Extended venothromboprophylaxis (eVTP) after abdominal surgery for hepatobiliary (HPB) and upper gastrointestinal (UGI) malignancies is recommended. Safety, efficacy and compliance within this group of surgical patients are not well described. The primary aim was to assess safety and compliance of post-operative administration of eVTP with low molecular weight heparin. Secondary aim was to assess barriers to treatment and monitor the rate of post-operative venous thromboembolism. METHODS: A prospective observational cohort study of patients undergoing abdominal surgery for HPB or UGI malignancies was undertaken from January 2014 to June 2016. All patients were assessed for eVTP. Demographics, clinical outcomes and clinical questionnaires on discharge and at follow-up 6 weeks post their initial surgery were used to assess the safety, compliance and efficacy of eVTP. RESULTS: A total of 100 patients were assessed for post-operative eVTP. Of these, 80 patients were prescribed 28 days of low molecular weight heparin. Of 80 patients, 65 (85%) patients completed the full eVTP, 11 (13%) missed 1-5 injections and only four (6%) missed 6-15 injections. In the 80 eVTP patients, there were no episodes of significant bleeding or venous thromboembolism. A total of nine (11%) patients would be unwilling to undertake eVTP again for a variety of reasons, including ease of disposal of syringes and needle phobias. CONCLUSION: The administration of eVTP in patients undergoing major HPB and UGI surgery is safe, with minimal morbidity and high compliance. The greatest barrier to administration is doctor prescription.
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Procedimientos Quirúrgicos del Sistema Digestivo/efectos adversos , Neoplasias/cirugía , Complicaciones Posoperatorias/prevención & control , Tromboembolia Venosa/prevención & control , Adulto , Anciano , Anciano de 80 o más Años , Anticoagulantes/administración & dosificación , Anticoagulantes/uso terapéutico , Enfermedades del Sistema Digestivo/patología , Enfermedades del Sistema Digestivo/cirugía , Procedimientos Quirúrgicos del Sistema Digestivo/normas , Femenino , Enfermedades Gastrointestinales/patología , Enfermedades Gastrointestinales/cirugía , Heparina de Bajo-Peso-Molecular/administración & dosificación , Heparina de Bajo-Peso-Molecular/uso terapéutico , Humanos , Masculino , Metaanálisis como Asunto , Persona de Mediana Edad , Morbilidad/tendencias , Neoplasias/complicaciones , Cooperación del Paciente/psicología , Cooperación del Paciente/estadística & datos numéricos , Estudios Prospectivos , Ensayos Clínicos Controlados Aleatorios como Asunto , Seguridad , Resultado del Tratamiento , Tromboembolia Venosa/epidemiología , Tromboembolia Venosa/etiologíaRESUMEN
Hospitalized acute medically ill patients are vulnerable to venous thromboembolism (VTE), known as hospital-acquired thrombosis (HAT). The elevated risk of HAT is usually due to a combination of factors, with immobility and a prothrombotic state due to acute illness being the most frequent. The HAT risk persists well after hospital discharge, with more than half of events occurring after patient release. These HAT events may be fatal, and patients who survive the initial event may be subject to VTE recurrence, chronic discomfort from post-thrombotic syndrome and, although rare, may develop chronic thrombo-embolic pulmonary hypertension, which is often debilitating. The risk of HAT can be reduced with effective thromboprophylaxis. Current guidelines recommend thromboprophylaxis with subcutaneous heparin, low molecular weight heparin (LMWH) or fondaparinux for at-risk acute medically ill patients, but reports of real-world practice indicated that some patients do not receive protection in the short-term as outlined by the guidelines. Previous studies that have assessed extended thromboprophylaxis for 4-5 weeks with LMWH or direct oral anticoagulants in medically ill patients found they did not offer a net clinical benefit; any demonstrated efficacy was outweighed by the significantly increased risk of major haemorrhage. Therefore, there is an ongoing need for improved VTE prevention without increasing the risk of bleeding. In the APEX trial, conducted in an acute medically ill population, betrixaban provided a significant reduction in VTE events after 35 to 42 days of treatment compared with short-term enoxaparin without an increase in major bleeding.
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Acutely ill hospitalized medical patients are at high risk of venous thromboembolism (VTE). Although thromboprophylaxis in these patients is recommended since 2004 by the American College of Chest Physicians, it is widely underused. The doubt as to whether or not to treat patients at high VTE risk after hospital discharge came from the knowledge that this risk may persist after the hospital admission period. Two meta-analyses comparing extended- versus short-duration prophylaxis are published. The results demonstrate an unfavorable balance between VTE prevention and incidence of major bleeding in patients assigned to extended-duration thromboprophylaxis. Only in the APEX study, betrixaban, a direct inhibitor of factor Xa, shows similar efficacy and safety compared to enoxaparin. However, while it is very promising, oral anticoagulant phase III studies and post-marketing registers are lacking. Moreover, betrixaban has a long half-life, an excretion in the gut by means of P-glycoprotein, and the lack of an antidote. These characteristics and the meta-analysis results prompt us to answer no to the extended thromboprophylaxis in hospitalized medical patients, at least now.