Structured benefit-risk assessment for enoxaparin, in the context of its label extension, for the extended treatment of deep vein thrombosis and pulmonary embolism, and prevention of its recurrence in patients with active cancer.

PURPOSE: Guidelines recommend low-molecular-weight heparins (LMWHs) for patients with cancer-associated thrombosis. However, until recently, only dalteparin and tinzaparin were approved in the European Economic Area (EEA) for these patients. This study compares the benefit-risk profile of enoxaparin with dalteparin and tinzaparin for the extended treatment of deep vein thrombosis (DVT) and pulmonary embolism (PE), and prevention of recurrence in adult patients with active cancer. METHODS: A semi-quantitative structured benefit-risk assessment was conducted for the label-extension application of enoxaparin based on the benefit-risk action team descriptive framework: define decision context; determine key benefit and risk outcomes; identify data sources; extract data; interpret results. RESULTS: The key benefits were defined as reduced all-cause mortality and venous thromboembolism (VTE) recurrence (including symptomatic DVT, fatal PE or non-fatal PE); the key risks were major and non-major bleeding of clinical significance, and heparin-induced thrombocytopenia (HIT). Enoxaparin demonstrated comparable effects for the reduction of VTE recurrence and all-cause mortality versus other EEA-approved LMWHs (dalteparin, tinzaparin). There was no evidence of a significant difference between enoxaparin and the comparator groups with regard to incidence of major and non-major bleeding. The data on HIT were too limited to assess the difference between the two groups. CONCLUSIONS: The assessment demonstrated a favourable benefit-risk profile for enoxaparin similar to that of other EEA-approved LMWHs for the treatment of DVT and PE and the prevention of recurrence in patients with active cancer and thus supported the label-extension approval.

Venous Thromboembolism: Review of Clinical Challenges, Biology, Assessment, Treatment, and Modeling.

Venous thromboembolism (VTE) is a massive clinical challenge, annually affecting millions of patients globally. VTE is a particularly consequential pathology, as incidence is correlated with extremely common risk factors, and a large cohort of patients experience recurrent VTE after initial intervention. Altered hemodynamics, hypercoagulability, and damaged vascular tissue cause deep-vein thrombosis and pulmonary embolism, the two permutations of VTE. Venous valves have been identified as likely locations for initial blood clot formation, but the exact pathway by which thrombosis occurs in this environment is not entirely clear. Several risk factors are known to increase the likelihood of VTE, particularly those that increase inflammation and coagulability, increase venous resistance, and damage the endothelial lining. While these risk factors are useful as predictive tools, VTE diagnosis prior to presentation of outward symptoms is difficult, chiefly due to challenges in successfully imaging deep-vein thrombi. Clinically, VTE can be managed by anticoagulants or mechanical intervention. Recently, direct oral anticoagulants and catheter-directed thrombolysis have emerged as leading tools in resolution of venous thrombosis. While a satisfactory VTE model has yet to be developed, recent strides have been made in advancing in silico models of venous hemodynamics, hemorheology, fluid-structure interaction, and clot growth. These models are often guided by imaging-informed boundary conditions or inspired by benchtop animal models. These gaps in knowledge are critical targets to address necessary improvements in prediction and diagnosis, clinical management, and VTE experimental and computational models.

Analysis of one-year follow-up results and treatment costs of patients with PTE in a tertiary care center.

Introduction: Pulmonary thromboembolism (PTE) is a life-threatening disease, with substantial treatment-related complications, difficult follow-up, treatment compliance, and high costs. This study aimed to assess treatment costs with various maintenance therapy regimens, complications, and patient adherence to treatment over a one-year follow-up period. Materials and Methods: This observational, prospective study included 142 patients with PTE who received maintenance anticoagulation therapy between November 2020 and March 2023. The patients were observed at three-month intervals for a year. Possible treatment-related complications, recurrence, mortality, and treatment costs were recorded. Result: Our results showed that there was no significant difference in bleeding risk based on the drugs used for initial or maintenance treatment. In maintenance therapy, low-molecular-weight heparin (LMWH), warfarin, and direct oral anticoagulant (DOAC) treatment regimens had similar treatment adherence and comparable efficacy and safety in terms of recurrence and bleeding (p> 0.05). Four patients (2.8%) were diagnosed with chronic thromboembolic disease. The one-year mortality rate was 24.6% (n= 35), of which 82.9% (n= 29) occurred within the first three months. Hospital mortality rates with the different maintenance therapies were 8.8% in the LMWH group, 5.7% in the warfarin group, and 3.2% in the DOAC group. The annual cost of using LMWH was higher than that of rivaroxaban, apixaban, and warfarin (p< 0.001) while there was no significant cost difference between DOACs and warfarin (p> 0.05). Conclusions: In our study, the LMWH, warfarin, and DOAC treatment regimens had similar efficacy, safety, and patient compliance. In terms of cost, LMWH was the costliest while DOAC and warfarin were similar.

A multicentre observational study of the prevalence, management, and outcomes of subsegmental pulmonary embolism.

BACKGROUND: The incidence of subsegmental pulmonary embolism (SSPE) has increased with improvements in imaging technology. There is clinical equipoise for SSPE treatment, with conflicting evidence of improved mortality or reduced venous thromboembolism recurrence with anticoagulation. SSPE studies have significant heterogeneity and often lack adequately matched disease comparator groups. OBJECTIVES: To determine the prevalence, management, and outcomes of SSPE and compare them to patients with main, lobar, segmental, and no pulmonary embolism (PE). PATIENTS/METHODS: All adult patients undergoing CT pulmonary angiography (CTPA) between 2013 and 2019, at 3 UK hospitals were included in the study. CTPA reports were text mined for language relating to PE, and then further manually screened for the presence and anatomical location of PE. Patient groups were propensity matched by age, sex, and year of CTPA prior to analysis. 3-month outcomes of major bleeding, VTE recurrence, and death were recorded. RESULTS: 79 (3.8%) SSPEs were identified from 2,055 diagnoses of PE, and 14,300 CTPA reports. 44 (56%) of SSPEs were single artery emboli, 25 (32%) were multiple unilateral emboli, and 10 (13%) were multiple bilateral emboli. Mortality, VTE recurrence and major bleeding were similar at 3 months across all groups. 87.3% of SSPE imaging reports had an additional radiological diagnosis, with pleural effusion (30%), consolidation (19%), and cardiomegaly (19%) being the most common. CONCLUSION: The prevalence of SSPE was 3.8% of all PEs and there were a substantial number of additional radiological findings in the SSPE group that may have accounted for their symptoms.

Cost-of-Illness Analysis of Long-Term Health Care Resource Use and Disease Burden in Patients With Pulmonary Embolism: Insights From the PREFER in VTE Registry.

Background As mortality from pulmonary embolism (PE) decreases, the personal and societal costs among survivors are receiving increasing attention. Detailing this burden would support an efficient public health resource allocation. We aimed to provide estimates for the economic and disease burden of PE also accounting for long-term health care use and both direct and indirect costs beyond the acute phase. Methods and Results This is a cost-of-illness analysis with a bottom-up approach based on data from the PREFER in VTE registry (Prevention of Thromboembolic Events-European Registry in Venous Thromboembolism). We calculated direct (clinical events and anticoagulation) and indirect costs (loss of productivity) of an acute PE event and its 12-month follow-up in 2020 Euros. We estimated a disability weight for the 12-month post-PE status and corresponding disability adjusted life years presumably owing to PE. Disease-specific costs in the first year of follow-up after an incident PE case ranged between 9135 Euros and 10 620 Euros. The proportion of indirect costs was 42% to 49% of total costs. Costs were lowest in patients with ongoing cancer, mainly because productivity loss was less evident in this already burdened population. The calculated disability weight for survivors who were cancer free 12 months post-PE was 0.017, and the estimated disability adjusted life years per incident case were 1.17. Conclusions The economic burden imposed by PE to society and affected patients is considerable, and productivity loss is its main driver. The disease burden from PE is remarkable and translates to the loss of roughly 1.2 years of healthy life per incident PE case.

Comparison of Guidelines for Evaluation of Suspected Pulmonary Embolism in Pregnancy: A Cost-effectiveness Analysis.

BACKGROUND: Pulmonary embolism (PE) remains a leading cause of maternal mortality, yet diagnosis remains challenging. International diagnostic guidelines vary significantly in their recommendations, making it difficult to determine an optimal policy for evaluation. RESEARCH QUESTION: Which societal-level diagnostic guidelines for evaluation of suspected PE in pregnancy are an optimal policy in terms of its cost-effectiveness? STUDY DESIGN AND METHODS: We constructed a complex Markov decision model to evaluate the cost-effectiveness of each identified societal guidelines for diagnosis of PE in pregnancy. Our model accounted for risk stratification, empiric treatment, diagnostic testing strategies, as well as short- and long-term effects from PE, treatment with low-molecular-weight heparin, and radiation exposure from advanced imaging. We considered clinical and cost outcomes of each guideline from a US health care system perspective with a lifetime horizon. Clinical effectiveness and costs were measured in time-discounted quality-adjusted life years (QALYs) and US dollars, respectively. Strategies were compared using the incremental cost-effectiveness ratio (ICER) with a willingness-to-pay threshold of $100,000/QALY. One-way, multiway, and probabilistic sensitivity analyses were performed. RESULTS: We identified six international societal-level guidelines. Base-case analysis showed the guideline proposed by the American Thoracic Society and Society of Thoracic Radiology (ATS-STR) yielded the highest health benefits (22.90 QALYs) and was cost-effective, with an ICER of $7,808 over the guidelines proposed by the Australian Society of Thrombosis and Haemostasis and the Society of Obstetric Medicine of Australia and New Zealand (ASTH-SOMANZ). All remaining guidelines were dominated. The ATS-STR guideline-recommended strategy yielded an expected additional 2.7 QALYs/100 patients evaluated over the ASTH-SOMANZ. Conclusions were robust to sensitivity analyses, with the ATS-STR guidelines optimal in 86% of probabilistic sensitivity analysis scenarios. INTERPRETATION: The ATS-STR guidelines for diagnosis of suspected PE in pregnancy are cost-effective and generate better expected health outcomes than guidelines proposed by other medical societies.

Randomised controlled trial of a prognostic assessment and management pathway to reduce the length of hospital stay in normotensive patients with acute pulmonary embolism.

BACKGROUND: The length of hospital stay (LOS) for acute pulmonary embolism (PE) varies considerably. Whether the upfront use of a PE prognostic assessment and management pathway is effective in reducing the LOS remains unknown. METHODS: We conducted a randomised controlled trial of adults hospitalised for acute PE: patients were assigned either to a prognostic assessment and management pathway involving risk stratification followed by predefined criteria for mobilisation and discharge (intervention group) or to usual care (control group). The primary end-point was LOS. The secondary end-points were the cost of prognostic tests and of hospitalisation, and 30-day clinical outcomes. RESULTS: Of 500 patients who underwent randomisation, 498 were included in the modified intention-to-treat analysis. The median LOS was 4.0 days (interquartile range (IQR) 3.7-4.2 days) in the intervention group and 6.1 days (IQR 5.7-6.5 days) in the control group (p<0.001). The mean total cost of prognostic tests was EUR 174.76 in the intervention group, compared with EUR 233.12 in the control group (mean difference EUR -58.37, 95% CI EUR -84.34- to -32.40). The mean total hospitalisation cost per patient was EUR 2085.66 in the intervention group, compared with EUR 3232.97 in the control group (mean difference EUR -1147.31, 95% CI EUR -1414.97- to -879.65). No significant differences were observed in 30-day readmission (4.0% versus 4.8%), all-cause mortality (2.4% versus 2.0%) or PE-related mortality (0.8% versus 1.2%) rates. CONCLUSIONS: The use of a prognostic assessment and management pathway was effective in reducing the LOS for acute PE.

Cost-effectiveness of early placement of vena cava filters to prevent symptomatic pulmonary embolism in patients with contraindications to prophylactic anticoagulant.

INTRODUCTION: Vena cava filters have been used as a primary means to prevent symptomatic pulmonary embolism (PE) in trauma patients who cannot be anticoagulated after severe injury, but the economic implications for this practice remain unclear. METHODS: Using a healthcare system perspective to analyze the a priori primary outcome of the da Vinci trial, we report the cost-effectiveness of using vena cava filters as a primary means to prevent PE in patients who have contraindications to prophylactic anticoagulation after major trauma. RESULTS: Of the 240 patients enrolled, complete, prospectively collected, hospital cost data during the entire hospital stay - including costs for the filter, medical/nursing/allied health staff, medical supplies, pathology tests, and radiological imaging - were available in 223 patients (93%). Patients allocated to the filter group (n = 114) were associated with a reduced risk of PE (0.9%) compared to those in the control group (n = 109, 5.5%; p = 0.048); and the filter's benefit was more pronounced among those who could not be anticoagulated within 7 days (filter: 0% vs control: 16%, Bonferroni-corrected p = 0.02). Overall, the cost needed to prevent one PE was high (AUD $379,760), but among those who could not be anticoagulated within 7 days, the costs to prevent one PE (AUD $36,156; ~ USD $26,032) and gain one quality-adjusted life-year (AUD $30,903; ~ USD $22,250) were substantially lower. CONCLUSION: The cost of using a vena cava filter to prevent PE for those who have contraindications to prophylactic anticoagulation within 3 days of injury is prohibitive, unless such contraindications remain for longer than 7 days. (Australian New Zealand Clinical Trials Registry no.: ACTRN12614000963628).

Short-term Cost Comparison of Systemic Heparin Therapy vs. Catheter Directed Thrombolysis for the Treatment of Massive and Submassive Pulmonary Embolism with Long-Term Chronic Pulmonary Hypertension Cost Model.

INTRODUCTION: Pulmonary embolism (PE) is a significant disease process that affects an estimated 117 cases per 100,000 person-years. Chronic pulmonary hypertension (CPH) is a long-term complication associated with acute PE which has a significant cost to treat, ranging from $98,000-117,000. METHODS: A retrospective chart review of 341 patients from January 2011 to November 2018 who presented with massive or submassive PE and were treated with either systemic heparin therapy or catheter directed thrombolysis (CDT). The results of the short-term cost analysis and pulmonary hypertension rates from data collected was then used in a long-term cost model using a standardized 100 patient model. RESULTS: Treatment with CDT resulted in fewer bleeding complications (4.2 percent vs. 13.8 percent, p=0.005), a shorter length of stay, a greater percentage of patients returning to their prior living conditions (89.0 percent vs. 79.3 percent, p=0.042), and a lower rate of chronic pulmonary hypertension at 12 months (6.3 percent vs. 15.9 percent, p=0.030) than those treated with systemic heparin. The expense of treatment utilizing CDT was greater than those undergoing systemic heparin treatment with a difference of approximately $31,000 (p=0.001) though our cost model showed the heparin group to have a higher cost over time. CONCLUSIONS: For patients with massive or submassive PE, this study demonstrated a significant long-term cost savings and improved outcomes for patients treated with catheter directed thrombolysis when compared to systemic heparin administration.

Post-acute pre-discharge echocardiography in the long-term prognostic assessment of pulmonary thrombembolism.

The aim of our study was to asses the long-term prognostic impact of post-acute, pre-discharge echocardiographic assessment of right ventricular (RV) dysfunction in patients with low- and intermediate-risk pulmonary embolism (PE). Consecutive patients with acute PE underwent post-acute, pre-discharge echocardiographic assessment of RV dysfunction (defined by: RV dilation, tricuspid anulus peak systolic excursion, or tricuspid regurgitation systolic velocity). A Cox multivariate survival mode was constructed to determine the prognostic impact of post-acute, pred-discharge RV dysfunction on all-cause mortality. 615 patients were included: 330 (54%) women, mean age 64 ± 18 years, 265 (43.1%) with post-acute, predischarge RV dysfunction. During follow-up (median 1068 days), 88 (14.3%) patients died. On Cox multivariate analyis, pre-discharge post-acute tricuspid regurgitation systolic velocity emerged as the only independent echocardiographic predictor of mortality (HR 1.73 for every 1 m/s increase; 95% confidence interval 1.033-2.897; p = 0.037). RV dysfunction persists in almost one half of PE patients in the post-acute phase on pre-discharge echocardiography; however, only tricuspid regurgitation systolic velocity independently predicts long-term prognosis.

Bleeding, death, and costs of care during hospitalization for acute pulmonary embolism: Insights from the Saint Luke's Outcomes of Pulmonary Embolism (SLOPE) study.

Limited data exist that comprehensively describe the practical management, in-hospital outcomes, healthcare resource utilization, and rates of post-hospital readmission among patients with submassive and massive pulmonary embolism (PE). Consecutive discharges for acute PE were identified from a single health system over 3 years. Records were audited to confirm presence of acute PE, patient characteristics, disease severity, medical treatment, and PE-related invasive therapies. Rates of in-hospital major bleeding and death, hospital length of stay (LOS), direct costs, and hospital readmission are reported. From January 2016 to December 2018, 371 patients were hospitalized for acute massive or submassive PE. In-hospital major bleeding (12.1%) was common, despite low utilization of systemic thrombolysis (1.8%) or catheter-directed thrombolysis (3.0%). In-hospital death was 10-fold higher among massive PE compared to submassive PE (36.6% vs 3.3%, p < 0.001). Massive PE was more common during hospitalizations not primarily related to venous thromboembolism, including hospitalizations primarily for sepsis or infection (26.8% vs 8.2%, p = 0.001). Overall, the median LOS was 6.0 days (IQR, 3.0-11.0) and the median standardized direct cost of admissions was $10,032 (IQR, $4467-$20,330). Rates of all-cause readmission were relatively high throughout late follow-up but did not differ between PE subgroups. Despite low utilization of thrombolysis, in-hospital bleeding remains a common adverse event during hospitalizations for acute PE. Although massive PE is associated with high risk for in-hospital bleeding and death, those successfully discharged after a massive PE demonstrate similar rates of readmission compared to submassive PE into late follow-up.

Outpatient Treatment in Low-Risk Pulmonary Embolism Patients Receiving Direct Acting Oral Anticoagulants Is Associated With Cost Savings.

Direct oral anticoagulants (DOAC) are first line treatment for pulmonary embolism (PE). Treatment of acute PE is traditionally hospital based and associated with high costs. The aims of this study were to evaluate potential cost savings with outpatient DOAC treatment compared to inpatient DOAC treatment in patients with low risk PE. A retrospective study in patients with DOAC treated low risk PE (simplified pulmonary severity index [sPESI] ≤ 1) admitted to 8 hospitals during 2013-2015. Health care costs were compared in 223(44%) patients treated as outpatients and 287(56%) treated in hospital. Total cost per patient was 8293 EUR in the inpatient group, and 2176 EUR in the outpatient group (p < 0.001). Total costs for inpatients were higher (p < 0.001) compared to outpatients in both subgroups with sPESI 0 and 1. In multivariate analysis, type of treatment (in- or outpatient, p = < 0.001) and sPESI group (0 or 1, p = < 0.001) were associated with total cost below or above median, whereas age (p = 0.565) and gender (p = 0.177) was not. Adherence to guidelines recommending outpatient treatment with DOAC in patients with low risk PE enables significant savings.

[The cost of pulmonary thromboembolism treatment]. / Pulmoner tromboemboli tedavisinde maliyet.

INTRODUCTION: Primary aim of this study is to determine the financial burden of Vitamin K Antagonists (VKA), low molecular weight heparins (LMWH) and new oral anticoagulants (NOAC) which are used in the treatment of the pulmonary thromboembolism (PTE). Secondary aim is to show long term complications of the treatment options. MATERIALS AND METHODS: The patients who are diagnosed with PTE between May 2016 and March 2018 at Faculty of Medicine Karadeniz Technical University Hospital were observed prospectively. Hospitalization costs were calculated on patients who were treated only for PTE by hospitalized in the Chest Diseases Service in the acute period. Maintenance costs were calculated over all patients who regulary admitted to our outpatient clinic with the diagnosis of PTE. Data were presented as mean ± SD and median ± interquartilee range. A p-value of <0.05 was accepted to be significant. RESULT: Fifty five (37.2%) of the patients were male, 93 (62.8%) were female and the median age was 68 (range 18-95). The median hospitalization time and cost of patients who are discharged with VKA (n: 22) compared with patients discharged with LMWH (n: 22) was found to be increased (1316.82 TL 7,5 days / 803.36 TL, 5 days p<0.001). Statistical analysis could not be performed with NOAC (n: 2). In the analysis of sixth month costs, LMWH cost was found to be higher than VKA cost (6.927.15 ± 2.687.67 TL/698.29 ± 483.51 TL p<0.001). However VKA treatment tended to be less expensive than treatment with NOACs (698.29 ± 483.51 TL/1.050.81 ± 300.28 TL p= 0.140). CONCLUSIONS: In the acute period of PTE, VKA increases the length of hospitalization and hospital costs in patients treated at the hospital. In the maintenance period, VKA tends to have a lower cost compared to NOACs.

Riociguate para Hipertensão Pulmonar Tromboembólica Crônica Inoperável ou Persistente/Recorrente após tratamento cirúrgico / Riociguate for Chronic Thromboembolic Pulmonary Hypertension Inoperable or Persistent/Recurring after Treatment Surgical

INTRODUÇÃO: A HPTEC é uma doença rara, até o momento sem um tratamento medicamentoso eficaz. A HPTEC não possui indicação de tratamento específico no atual Protocolo Clínico e Diretrizes Terapêutica para Hipertensão Arterial Pulmonar. O tratamento primário é a cirurgia para retirada mecânica do trombo localizado na artéria pulmonar e seus ramos (endarterectomia pulmonar). O tratamento com Riociguate é indicado em bula para um grupo restrito de pacientes com HPTEC, aqueles considerados inoperáveis ou que desenvolvam hipertensão pulmonar residual ou recidivas após a endarterectomia pulmonar. PERGUNTA: O Riociguate é seguro, eficaz e custo-efetivo quando comparado ao placebo para os pacientes com HPTEC inoperável/residual/recidivante? TECNOLOGIA: Riociguate (Adempas®). EVIDÊNCIAS CIENTÍFICAS: A literatura é restrita, apenas um ensaio clínico randomizado (ECR), o CHEST-1. Estudo multicêntrico, duplo cego, incluiu 261 pacientes com HPTEC inoperável ou recorrente persistente randomizados 1:2 para placebo e riociguate. O desfecho primário foi a mudança obtida no teste de caminhada de seis minutos (TC6M) ao final de 16 semanas. Houve um aumento no TC6M de 39 metros no grupo intervenção enquanto no grupo placebo houve uma redução de 6 metros (diferença média de 46 metros; intervalo de confiança (IC) 95%, 25 a 67 metros; p < 0,001). A resistência vascular pulmonar diminuiu em 226 dyn · sec · cm­5 no grupo intervenção e aumentou em 23 dyn · sec · cm­5 no grupo controle (diferença média ­ 246 dyn · sec · cm­5; IC95% ­303 a ­190; p < 0,001). O grupo do Riociguate também apresentou melhora significativa no nível do BNP (p < 0,001) e CF (p = 0.003). Os eventos adversos (EA) mais graves foram insuficiência ventricular direita (3% em cada grupo) e síncope (2% no grupo intervenção e 3% no grupo placebo). Além do ECR CHEST-1, foi incluído o estudo de extensão aberta (CHEST-2). Nesta, 237 pacientes provenientes do CHEST-1 foram acompanhados por uma mediana de 116 semanas, todos em uso de Riociguate. O medicamento foi considerado eficaz para os desfechos funcionais (CF e TC6M), escala de Borg e de qualidade de vida (Living with pulmonary hypertension questionnaire e EQ-5D-3L). Os EA foram, em sua maioria, leves: 28% nasofaringite, 23% edema periférico, 22% tontura, 18% diarreia, 16% tosse, 10% síncope, 8% hipotensão e 5% hemoptise. AVALIAÇÃO ECONÔMICA: O demandante apresentou uma análise de custo-efetividade com base em um modelo de Markov cuja Razão de Custo-Efetivdade Incremental (RCEI) média foi estimada em R$ 402.569,52/QALY. O novo modelo, apresentado pelo parecerista externo, apresentou uma RCEI maior: R$ 816.089,17/QALY, mesmo considerando o desconto no preço do comprimido (R$ 90,32). AVALIAÇÃO DE IMPACTO ORÇAMENTÁRIO (AIO): O demandante estimou um impacto orçamentário em 5 anos de R$ 438.398.520,36. O impacto orçamentário foi considerado subestimado, principalmente em relação ao número de casos de embolia pulmonar, estimativa inicial de 50 por 100 mil, revisada para 112 por 100 mil, gerando uma nova estimativa no valor de 889.546.200,08 em 5 anos. MONITORAMENTO DO HORIZONTE tecnológico: detectaram-se dois medicamentos potenciais para o tratamento dos pacientes com HPTEC inoperável ou persistente/recorrente, macintentana e selexipague, ambos sem registro na Agência Nacional de Vigilância Sanitária. MONITORAMENTO DO HORIZONTE TECNOLÓGICO: detectaram-se dois medicamentos potenciais para o tratamento dos pacientes com HPTEC inoperável ou persistente/recorrente, macintentana e selexipague, ambos sem registro na Agência Nacional de Vigilância Sanitária. CONSIDERAÇÕES: A decisão de incorporação baseada em um único ECR é sujeita a erros. Não há provas de aumento da sobrevida com o Riociguate. O benefício está relacionado principalmente a desfechos substitutos. O modelo econômico de custo-efetividade apresentou limitações como a superestimação do beneficio do riociguate e a subestimação do tratamento atual. O impacto orçamentário foi considerado subestimado. RECOMENDAÇÃO PRELIMINAR: Em sua 83ª reunião ordinária, no dia 6 de novembro de 2019, a Conitec recomendou a não incorporação no SUS do riociguate para o tratamento da hipertensão pulmonar tromboembólica crônica inoperável ou persistente/recorrente. Considerou-se as incertezas nas evidências apresentadas em relação à eficácia, principalmente a longo prazo, e fragilidades nos estudos econômicos apresentados. CONSULTA PÚBLICA: Foram recebidas 3.384 contribuições, sendo a maioria (61%) de "interessados no tema", 13% de profissionais da sáude e as demais contribuições provenientes de pacientes ou cuidadores. A maioria (88%) discordou da resolução inicial. A Conitec entendeu que não houve argumentação suficiente para alterar sua recomendação inicial. RECOMENDAÇÃO FINAL: Os membros da Conitec presentes na 86 ª reunião ordinária, no dia 05 de março de 2020, deliberaram, por unanimidade, por recomendar a não incorporação no SUS do Riociguate em pacientes com HPTEC inoperável ou persistente/recorrente. Foi assinado o Registro de Deliberação nº 510/2020. DECISÃO: não incorporar Riociguate para hipertensão pulmonar tromboembólica crônica inoperável ou persistente/recorrente após tratamento cirúrgico, no âmbito do Sistema Único de Saúde - SUS, conforme a Portaria nº 11, publicada no Diário Oficial da União nº 62, seção 1, página 77, em 31 de março de 2020.

Cost-effectiveness microsimulation of catheter-directed thrombolysis in submassive pulmonary embolism using a right ventricular function model.

Approximately 30-50% of hemodynamically stable patients presenting with acute pulmonary embolism (PE) have evidence of right ventricular (RV) dysfunction. These patients are classified as submassive PE and the role of reperfusion therapy remains unclear. We sought to identify the circumstances under which catheter-directed thrombolysis (CDT) would represent high-value care for submassive PE. We used a computer-based, individual-level, state-transition model with one million simulated patients to perform a cost-effectiveness analysis comparing the treatment of submassive PE with CDT followed by anticoagulation to treatment with anticoagulation alone. Because RV function impacts prognosis and is commonly used in PE outcomes research, our model used RV dysfunction to differentiate health states. One-way, two-way, and probabilistic sensitivity analyses were used to quantify model uncertainty. Our base case analysis generated an incremental cost-effectiveness ratio (ICER) of $119,326 per quality adjusted life year. Sensitivity analyses resulted in ICERs consistent with high-value care when CDT conferred a reduction in the absolute probability of RV dysfunction of 3.5% or more. CDT yielded low-value ICERs if the absolute reduction was less than 1.56%. Our model suggests that catheter-directed thrombolytics represents high-value care compared to anticoagulation alone when CDT offers an absolute improvement in RV dysfunction of 3.5% or more, but there is substantial uncertainly around these results. We estimated the monetary value of clarifying the costs and consequences surrounding RV dysfunction after submassive PE to be approximately $268 million annually, suggesting further research in this area could be highly valuable.

Invasive hemodynamic assessment of patients with submassive pulmonary embolism.

OBJECTIVES: To investigate the invasive hemodynamics in patients with intermediate-risk pulmonary embolism (PE) and the change that occurs with catheter-directed thrombolysis (CDT). BACKGROUND: Intermediate-risk PE is associated with right ventricular strain and worse outcomes yet the invasive hemodynamics have not been well described. METHODS: Ninety-two consecutive patients with intermediate-risk PE referred for CDT at two tertiary medical centers with Pulmonary Embolism Response Teams were included in this prospective cohort study. Hemodynamics at baseline and after CDT therapy was measured. Patients with cardiac index (CI) ≤1.8 L min-1 m-2 were compared to those without shock (CI > 1.8). Linear regression analysis was performed to study the relationship between clinical variables and low CI. RESULTS: Thirty-seven out of 92 (40%) had a CI less than 1.8 L min-1 m-2 . When comparing the low CI to the normal CI groups, most demographics, vital signs, biomarkers, and PE severity index (PESI) scores were similar. The low CI group had more females and slightly lower systolic blood pressures although still in the normal range (122 vs. 132 mmHg, p = .026). Treatment with CDT was associated with significant improvement in CI, heart rate, and pulmonary artery pressures in both groups. Linear regression analysis did not reveal a strong correlation between CI and noninvasive metrics such as heart rate, blood pressure, or PESI score. CONCLUSIONS: Forty percent of patients with submassive PE had a depressed CI and treatment with CDT lead to hemodynamic improvements. Invasive hemodynamics may help better identify higher risk patients and guide therapy.

Total costs of treating venous thromboembolism: implication of different cost perspectives in a Danish setting.

Aim: Optimal use of scarce resources is a focus in the healthcare sector, as resources devoted to health care are limited. Costs and health economic analyses can help guide decision-making concerning treatments. One important factor is the choice of cost perspective that can range from a focus on narrow drug budget costs to broader economic perspectives. In the case of treatment with oral anticoagulants in patients with venous thromboembolism (VTE), encompassing deep vein thrombosis and pulmonary embolism, the aim of this cost analysis was to illustrate the differences in costs when applying different cost perspectives.Methods: In a cost analysis, pairwise comparisons of average costs of 6 months standard treatment with either a low molecular weight heparin parenteral anticoagulant (LMWH) and a Vitamin K Antagonist (VKA) versus one of the non-vitamin K oral anticoagulants [NOACs; dabigatran etexilate, rivaroxaban, apixaban, and edoxaban) used in daily clinical practice in Denmark for VTE patients were carried out. Each analysis included the results from five different cost analyses with increasingly broader cost perspectives going from the narrowest "drug cost only" perspective to the broadest "societal" perspective.Results: Focusing on "drug costs only", LMWH/VKA was associated with the lowest costs compared to all NOACs. However, including the economic impact of preventing recurrent VTE and limit bleedings, apixaban and rivaroxaban resulted in slightly lower health care costs than LMWH/VKA. When applying the "societal perspective", the total costs saved with apixaban and rivaroxaban compared to LMWH/VKA further increased, with apixaban having the lowest total costs.Conclusions: The present study's case of oral anticoagulants in VTE treatment illustrated the importance of the cost perspective in the choice of therapy. If decision-making were based on drug costs only, instead of applying a health care sector or societal cost perspective, suboptimal decisions may be likely.

Usefulness of right ventricular strain assessment in submassive pulmonary thromboembolism undergoing ultrasound-facilitated thrombolysis.

Massive and submassive pulmonary thromboembolism carry significant morbidity and mortality. We present an elderly female who was diagnosed with a submassive pulmonary embolism by computed tomographic angiography and treated with ultrasound-facilitated thrombolysis (UFT). This case demonstrates the usefulness of right ventricular longitudinal strain measurements by two-dimensional speckle tracking echocardiography in the evaluation of right ventricular function before and after UFT. Evaluation of right ventricle longitudinal strain by speckle tracking echocardiography may supplement other parameters in the assessment of right ventricular function in these patients.

Assessment of the association between pre-treatment and post-treatment left atrium size and severity of disease in patients with acute pulmonary embolism by using computed tomography pulmonary angiography.

INTRODUCTION: As far as we know, left atrium (LA) imaging findings of pre-treatment and post-treatment nonmassive, submassive and massive acute pulmonary embolism (APE) have not been reported in literature. The aim of this study is to assess LA sizes of nonmassive, submassive and massive APE before and after treatment with computed tomography pulmonary angiography (CTPA) and to research whether there are differences between groups. MATERIALS AND METHODS: Sixty two adult APE patients (21 nonmassive, 31 submassive and 10 massive) who were diagnosed with CTPA and who had post-treatment follow-up images and recorded clinical information were included in the study. Pre-treatment and post-treatment LA sizes of all groups were measured by two radiologists independently. RESULT: The lowest pre-treatment LA size was found in massive APE and this difference was found to be statistically significant when compared with submassive (p= 0.001) and nonmassive (p< 0.001) groups. In addition, submassive APE patients were found to have lower LA size when compared with nonmassive APE patients (p= 0.006). In massive and submassive APE, post-treatment LA sizes were found to be statistically significantly higher when compared with pre-treatment (p< 0.001 for both groups). However, in nonmassive APE patients, pre-treatment and post-treatment LA size difference was not found to be statistically significant (p= 0.082). CONCLUSIONS: As the severity of APE increases, LA size decreases. Thus, a decrease LA size during APE can show increased APE severity. This study reported that LA size increased statistically in post-treatment massive and submassive APE patients when compared with pre-treatment. These results suggest that in APE patients, as a response to treatment, LA size can be an additional parameter reflecting the changes in cardiac morphology.

Retrospective comparison of ultrasound facilitated catheter-directed thrombolysis and systemically administered half-dose thrombolysis in treatment of pulmonary embolism.

This study retrospectively compared the outcomes of patients who received ultrasound facilitated catheter-directed thrombolysis (UFCDT) versus systemically administered 'half-dose' thrombolysis (HDT) in 97 patients with PE. The outcomes assessed included changes in baseline pulmonary artery systolic pressure (PASP), right ventricle/left ventricle ratio (RV/LV), cost and duration of hospitalization, death, bleeding, and recurrent venous thromboembolism in the short and intermediate term follow-up. Analyses were performed using a covariance adjustment propensity score approach to address baseline differences between groups in variables associated with PASP and RV/LV, covarying baseline scores. The baseline mean ± SE PASP dropped from 49.3 ± 1.1 to 32.5 ± 0.3 mmHg at 36 hours in the HDT group, and from 50.6 ± 1.2 to 35.1 ± 0.4 mmHg in the UFCDT group; group × time interaction p-value = 0.007. Corresponding drops in the RV/LV were from a baseline of 1.26 ± 0.05 to 1.07 ± 0.01 in the HDT group and from 1.30 ± 0.05 to 1.14 ± 0.01 in the UFCDT group at 36 hours; group × time interaction p-value = 0.269. Statistically significant decreases were noted in PASP and RV/LV for both the HDT and UFCDT at 36 hours and follow-up. PASP through follow-up was significantly lower in the HDT than the UFCDT group. Likewise, RV/LV was lower in the HDT group. The duration and cost of hospitalization were lower in the HDT group (6.2 ± 1.4 days vs 1.9 ± 0.3 days, p < 0.001; US$12,000 ± $3000 vs $74,000 ± $6000, p < 0.001). We conclude that both UFCDT and HDT lead to rapid reduction of PASP and RV/LV, whereas HDT leads to a lower duration and cost of hospitalization.