Evaluación de la eficacia y seguridad de la trombectomía mecánica con catéter de tromboaspiración en pacientes con ictus isquémico agudo que cumplen con los criterios de trombectomía mecánica pero no son tributarios a tratamiento endovenoso con alteplasa / Evaluation of the efficacy and safety of mechanical thrombectomy with a thromboaspiration catheter in patients with acute ischemic stroke who meet the criteria for mechanical thrombectomy but are not eligible for intravenous treatment with alteplase

ANTECEDENTES: El presente documento expone la evaluación de la eficacia y seguridad de la trombectomia mecánica (TM) con catéter de tromboaspiración (CTA), en pacientes con ictus isquémico agudo (IIA) que cumplen con los criterios de TM, pero no son tributarios al tratamiento endovenoso con alteplasa (TEA)1. A través de la Carta N°4287-GRPAESSALUD-2019, los médicos especialistas del Servicio de Neurorradiología, del Hospital Nacional Guillermo Almenara Irigoyen (HNGAI), a través de la gerencia de la Red Prestacional Almenara, solicitan al Instituto de Evaluación de Tecnologías en Salud e Investigación (IETSI) la evaluación de uso del "Catéter para trombo aspiración 6 FR 132 CM de longitud", que para efectos del presente dictamen preliminar será llamado "catéter de tromboaspiración"2, en pacientes con IIA que acuden al hospital luego de las 4.5 horas de iniciado el evento, por lo que descalifican para ser atendidos con TEA, o aquellos con contraindicación para el uso de este medicamento. ASPECTOS GENERALES: Los aspectos relacionados a la epidemiología y consecuencias del IIA han sido abordados en el documento resumen ad hoc del IETSI titulado: "Eficacia y seguridad de la trombectomía mecánica con stent recuperable en pacientes con ictus isquémico agudo que cumplen con los criterios de trombectomía mecánica pero no son tributarios a tratamiento endovenoso con alteplasa". Según las recomendaciones de guías de práctica clínica (GPC) internacionales como de la AHA/ASA (Powers, AA, et al. 2019), los pacientes con IIA, solo pueden recibir TEA de manera eficaz y segura hasta las 4.5 horas de iniciado el evento. Luego de esta ventana el uso de TEA podría incrementar el potencial de daño al paciente. Asimismo, la GPC en mención establece contraindicaciones adicionales para el uso de TEA', por lo que este subgrupo tampoco podría ser tratado con este fármaco incluso si acudieran a emergencia dentro de las 4.5 horas de iniciado el IIA. METODOLOGÍA: Se realizó una búsqueda sistemática de información con el objetivo de identificar la mejor evidencia disponible sobre la eficacia y seguridad de la TM con CTA en comparación con la TE, en pacientes con IIA que cumplen con los criterios de TM, pero que no son tributarios a TEA. Además, se buscó evidencia que compare a los dispositivos CTA vs. SR para procedimientos de TM en la misma población objetivo. La búsqueda bibliográfica' se realizó en las bases de datos de PubMed, The Cochrane Library y LILACS. Asimismo, se realizó una búsqueda manual en Google y dentro de las páginas web pertenecientes a grupos que realizan GPC y Evaluaciones de Tecnologías Sanitarias (ETS), incluyendo, el National Institute for Health and Care Excellence (NICE), Canadian Agency for Drugs and Technologies in Health (CADTH), Scottish Medicines Consortium (SMC), Scottish Intercollegiate Guidelines Network (SIGN), Institute for Clinical and Economic Review (ICER), Instituto de Calidad y Eficiencia en la Atención de la Salud (IQWiG, por sus siglas en alemán), la Base Regional de Informes de Evaluación de Tecnologías en Salud de las Américas (BRISA), la Organización Mundial de la Salud (OMS), el Ministerio de Salud del Perú (MINSA) y el Instituto de Evaluación de Tecnologías en Salud e Investigación (IETSI). Además, se realizó una búsqueda de GPC de las principales sociedades o instituciones especializadas en el manejo terapéutico de pacientes con IIA como: la American Heart Association (AHA), American Stroke Association (ASA), European Stroke Organization (ESO), European Society of Minimally Invasive Neurological Therapy (ESMINT) y la National Stroke Foundations (NSF). Por último, se realizó una búsqueda de estudios clínicos en ejecución o aún no terminados en ClinicalTrials.govy la International Clinical Trial Registry Platform (ICTRP). RESULTADOS: Luego de la búsqueda bibliográfica con fecha 29 de octubre de 2021, se identificaron 7 GPC: NSF8, AHA/ASA9, ESO/ESMINT10, NICE11, IETSI12, CSBP'3, y RCP14(National Stroke Foundation 2021, Powers, Rabinstein, et al. 2019, Turc et al. 2019, National Institute for Health and Care Excellence 2019, Instituto de Evaluación de Tecnologías en Salud e Investigación 2018, Boulanger et al. 2018, Royal College of Physicians 2016); y un ECA (Lapergue et al. 2017) que responden a la pregunta PICO de interés. Todas las GPC incluidas realizaron recomendaciones para el tratamiento con TM en pacientes con IIA, incluyendo a aquellos que acuden para recibir atención luego de las 4.5 horas de ocurrido el evento. Asimismo, solo dos de las GPC (CSBP y RCP) realizaron recomendaciones específicas en pacientes con contraindicaciones para uso de TEA. No se identificaron estudios que comparen la TM con CTA vs. laTE, o que evalúen solamente la TM con CTA en la población de interés. En cuanto a la comparación de la TM con CTA vs. SR en la población de pacientes elegibles para TM no tributarios a TEA, solo el ECA de Lapergue et al. (Lapergue et al. 2017) incluyó un subanálisis preespecificado en dicha población, para la evaluación del desenlace subrogado de tasas de revascularización exitosa. Sin embargo, no se cuenta con información de la eficacia y seguridad proveniente de estudios que comparen directamente estos dispositivos sobre desenlaces de relevancia clínica para esta población. CONCLUSIÓN: Por lo expuesto, el IETSI no aprueba es uso de catéter de tromboaspiración en pacientes con ictus isquémico agudo que cumplen con los criterios de trombectomía mecánica pero no son tributarios a tratamiento endovenoso con alteplasa. Además, se sugiere a los especialistas que, de existir alguna población específica con IIA que consideren como potencial beneficiario del dispositivo CTA, puedan enviar sus solicitudes debidamente justificadas para ser valoradas en una nueva ETS.

Evaluación de la eficacia y seguridad de la trombectomía mecánica con stent recuperable en pacientes con ictus isquémico agudo que cumplen con los criterios de trombectomía mecánica pero no son tributarios a tratamiento endovenoso con alteplasa / Evaluation of the efficacy and safety of mechanical thrombectomy with retrievable stent in patients with acute ischemic stroke who meet the criteria for mechanical thrombectomy but are not eligible for intravenous treatment with alteplase

ANTECEDENTES: El presente documento expone la evaluación de la eficacia y seguridad de la trombectomia mecánica (TM) con catéter de tromboaspiración (CTA), en pacientes con ictus isquémico agudo (IIA) que cumplen con los criterios de TM, pero no son tributarios al tratamiento endovenoso con alteplasa (TEA)1. A través de la Carta N°4287-GRPAESSALUD-2019, los médicos especialistas del Servicio de Neurorradiología, del Hospital Nacional Guillermo Almenara Irigoyen (HNGAI), a través de la gerencia de la Red Prestacional Almenara, solicitan al Instituto de Evaluación de Tecnologías en Salud e Investigación (IETSI) la evaluación de uso del "Catéter para trombo aspiración 6 FR 132 CM de longitud", que para efectos del presente dictamen preliminar será llamado "catéter de tromboaspiración"2, en pacientes con IIA que acuden al hospital luego de las 4.5 horas de iniciado el evento, por lo que descalifican para ser atendidos con TEA, o aquellos con contraindicación para el uso de este medicamento. ASPECTOS GENERALES: Los aspectos relacionados a la epidemiología y consecuencias del IIA han sido abordados en el documento resumen ad hoc del IETSI titulado: "Eficacia y seguridad de la trombectomía mecánica con stent recuperable en pacientes con ictus isquémico agudo que cumplen con los criterios de trombectomía mecánica pero no son tributarios a tratamiento endovenoso con alteplasa". Según las recomendaciones de guías de práctica clínica (GPC) internacionales como de la AHA/ASA (Powers, AA, et al. 2019), los pacientes con IIA, solo pueden recibir TEA de manera eficaz y segura hasta las 4.5 horas de iniciado el evento. Luego de esta ventana el uso de TEA podría incrementar el potencial de daño al paciente. Asimismo, la GPC en mención establece contraindicaciones adicionales para el uso de TEA', por lo que este subgrupo tampoco podría ser tratado con este fármaco incluso si acudieran a emergencia dentro de las 4.5 horas de iniciado el IIA. METODOLOGÍA: Se realizó una búsqueda sistemática de información con el objetivo de identificar la mejor evidencia disponible sobre la eficacia y seguridad de la TM con CTA en comparación con la TE, en pacientes con IIA que cumplen con los criterios de TM, pero que no son tributarios a TEA. Además, se buscó evidencia que compare a los dispositivos CTA vs. SR para procedimientos de TM en la misma población objetivo. La búsqueda bibliográfica' se realizó en las bases de datos de PubMed, The Cochrane Library y LILACS. Asimismo, se realizó una búsqueda manual en Google y dentro de las páginas web pertenecientes a grupos que realizan GPC y Evaluaciones de Tecnologías Sanitarias (ETS), incluyendo, el National Institute for Health and Care Excellence (NICE), Canadian Agency for Drugs and Technologies in Health (CADTH), Scottish Medicines Consortium (SMC), Scottish Intercollegiate Guidelines Network (SIGN), Institute for Clinical and Economic Review (ICER), Instituto de Calidad y Eficiencia en la Atención de la Salud (IQWiG, por sus siglas en alemán), la Base Regional de Informes de Evaluación de Tecnologías en Salud de las Américas (BRISA), la Organización Mundial de la Salud (OMS), el Ministerio de Salud del Perú (MINSA) y el Instituto de Evaluación de Tecnologías en Salud e Investigación (IETSI). Además, se realizó una búsqueda de GPC de las principales sociedades o instituciones especializadas en el manejo terapéutico de pacientes con IIA como: la American Heart Association (AHA), American Stroke Association (ASA), European Stroke Organization (ESO), European Society of Minimally Invasive Neurological Therapy (ESMINT) y la National Stroke Foundations (NSF). Por último, se realizó una búsqueda de estudios clínicos en ejecución o aún no terminados en ClinicalTrials.govy la International Clinical Trial Registry Platform (ICTRP). RESULTADOS: Luego de la búsqueda bibliográfica con fecha 29 de octubre de 2021, se identificaron 7 GPC: NSF8, AHA/ASA9, ESO/ESMINT10, NICE11, IETSI12, CSBP'3, y RCP14(National Stroke Foundation 2021, Powers, Rabinstein, et al. 2019, Turc et al. 2019, National Institute for Health and Care Excellence 2019, Instituto de Evaluación de Tecnologías en Salud e Investigación 2018, Boulanger et al. 2018, Royal College of Physicians 2016); y un ECA (Lapergue et al. 2017) que responden a la pregunta PICO de interés. Todas las GPC incluidas realizaron recomendaciones para el tratamiento con TM en pacientes con IIA, incluyendo a aquellos que acuden para recibir atención luego de las 4.5 horas de ocurrido el evento. Asimismo, solo dos de las GPC (CSBP y RCP) realizaron recomendaciones específicas en pacientes con contraindicaciones para uso de TEA. No se identificaron estudios que comparen la TM con CTA vs. laTE, o que evalúen solamente la TM con CTA en la población de interés. En cuanto a la comparación de la TM con CTA vs. SR en la población de pacientes elegibles para TM no tributarios a TEA, solo el ECA de Lapergue et al. (Lapergue et al. 2017) incluyó un subanálisis preespecificado en dicha población, para la evaluación del desenlace subrogado de tasas de revascularización exitosa15. Sin embargo, no se cuenta con información de la eficacia y seguridad proveniente de estudios que comparen directamente estos dispositivos sobre desenlaces de relevancia clínica para esta población. CONCLUSIÓN: Por lo expuesto, el IETSI no aprueba es uso de catéter de tromboaspiración en pacientes con ictus isquémico agudo que cumplen con los criterios de trombectomía mecánica pero no son tributarios a tratamiento endovenoso con alteplasa. Además, se sugiere a los especialistas que, de existir alguna población específica con IIA que consideren como potencial beneficiario del dispositivo CTA, puedan enviar sus solicitudes debidamente justificadas para ser valoradas en una nueva ETS.

Economic Evaluation of Endovascular Treatment for Acute Ischemic Stroke.

BACKGROUND AND PURPOSE: Endovascular treatment for acute ischemic stroke has been proven clinically effective, but evidence of the cost-effectiveness based on real-world data is scarce. The aim of this study was to assess whether endovascular therapy plus usual care is cost-effective in comparison to usual care alone in acute ischemic stroke patients. METHODS: An economic evaluation was performed from a societal perspective with a 2-year time horizon. Empirical data on health outcomes and the use of resources following endovascular treatment were gathered parallel to the MR CLEAN trial (Multicenter Randomized Clinical Trial of Endovascular Treatment for Acute Ischemic Stroke in the Netherlands) and its 2-year follow-up study. Incremental cost-effectiveness ratios were calculated as the extra costs per additional patient with functional independence (modified Rankin Scale score 0-2) and the extra cost per quality-adjusted life year gained. RESULTS: The mean costs per patient in the intervention group were $126 494 versus $143 331 in the control group (mean difference, -$16 839 [95% CI, -$38 113 to $5456]). Compared with patients in the control group, more patients in the intervention group achieved functional independence, 37.2% versus 23.9% (absolute difference, 13.3% [95% CI, 4.0%-22.0%]) and they generated more quality-adjusted life years, 0.99 versus 0.83 (mean difference of 0.16 [95% CI, 0.04-0.29]). Endovascular treatment dominated standard treatment with $18 233 saved per extra patient with a good outcome and $105 869 saved per additional quality-adjusted life year. CONCLUSIONS: Endovascular treatment added to usual care is clinically effective, and cost saving in comparison to usual care alone in patients with acute ischemic stroke. Registration: URL: https://www.trialregister.nl/trial/695; Unique identifier: NL695. URL: https://www.isrctn.com; Unique identifier: ISRCTN10888758.

Fast-track thrombolysis protocol for acute limb ischemia.

OBJECTIVE: Catheter-directed thrombolysis in the treatment of acute lower extremity arterial occlusions often requires several interventional sessions to generate successful outcomes. It is typically an expensive procedure, necessitating extended hospital length of stay (LOS) that may be associated with an increase in both local and systemic hemorrhagic complications. Five years ago, we created the fast-track thrombolysis protocol for arteries (FTTP-A) to deal with these concerns. The goal of our protocol is to re-establish patency during the first session of thrombolysis, thus decreasing costs and complications associated with prolonged periods of thrombolytic exposure. METHODS: A retrospective study of 42 patients who were treated for acute limb ischemia at our institution by FTTP-A from January 2014 to February 2019 was performed. FTTP-A includes periadventitial lidocaine injection at the arterial puncture site under ultrasound guidance, contrast arteriography of the entire targeted segment, pharmacomechanical rheolytic thrombectomy of the occluded arterial segment, tissue plasminogen activator infusion along the occluded segment, balloon maceration of the thrombus, and (if deemed necessary) placement of a stent in an area of significant (≥30%) stenosis that is refractory to balloon angioplasty and thrombolysis. After the stenosis or thrombus is cleared, patients are prescribed an oral anticoagulant agent. RESULTS: Primary FTTP-A (50 total interventions) was performed in 42 patients. The median age of patients was 67.2 ± 12.2 years (range, 41-98 years), and 54.8% were male; 59.5% of the procedures were performed on the left lower extremity. Initial arterial access was obtained through the common femoral artery in 39 of 42 cases (92.9%); in the remaining 3 cases, it was obtained in a left bypass access site, a right femoral-popliteal graft, and a right femoral-femoral graft. The mean operative time was 148.9 ± 62.9 minutes (range, 83-313 minutes), and the mean volume of tissue plasminogen activator infused was 9.7 ± 4.0 mg (range, 2-20 mg). The median cost including medications and interventional tools was $4673.19 per procedure. The mean postoperative LOS was 3.1 ± 4.5 days (range, 1-25 days). Median postoperative LOS was 1 day. Mean postoperative follow-up was 27 ± 19.2 months (range, 0-62 months). Single-session FTTP-A was successful in 81% (n = 34/42) of patients; the remaining 8 patients (19%) required a single additional session. Of the 42 patients, 34 (81%) required arterial stenting. Periprocedural complications consisted of one patient with hematuria, which resolved, and one patient with thrombocytopenia, which resolved. No patients experienced rethrombosis within 30 days of FTTP-A. During the 5-year study period, there was no significant local or systemic hemorrhage, limb loss, or mortality related to this protocol. CONCLUSIONS: FTTP-A appears to be a safe, efficacious, and cost-effective procedure in the resolution of acute lower extremity arterial occlusions.

Cost-Effectiveness of Tenecteplase Before Thrombectomy for Ischemic Stroke.

BACKGROUND AND PURPOSE: Tenecteplase improved functional outcomes and reduced the requirement for endovascular thrombectomy in ischemic stroke patients with large vessel occlusion in the EXTEND-IA TNK randomized trial. We assessed the cost-effectiveness of tenecteplase versus alteplase in this trial. METHODS: Post hoc within-trial economic analysis included costs of index emergency department and inpatient stroke hospitalization, rehabilitation/subacute care, and rehospitalization due to stroke within 90 days. Sources for cost included key study site complemented by published literature and government websites. Quality-adjusted life-years were estimated using utility scores derived from the modified Rankin Scale score at 90 days. Long-term modeled cost-effectiveness analysis used a Markov model with 7 health states corresponding to 7 modified Rankin Scale scores. Probabilistic sensitivity analyses were performed. RESULTS: Within the 202 patients in the randomized controlled trial, total cost was nonsignificantly lower in the tenecteplase-treated patients (40 997 Australian dollars [AUD]) compared with alteplase-treated patients (46 188 AUD) for the first 90 days(P=0.125). Tenecteplase was the dominant treatment strategy in the short term, with similar cost (5412 AUD [95% CI, -13 348 to 2523]; P=0.181) and higher benefits (0.099 quality-adjusted life-years [95% CI, 0.001-0.1967]; P=0.048), with a 97.4% probability of being cost-effective. In the long-term, tenecteplase was associated with less additional lifetime cost (96 357 versus 106 304 AUD) and greater benefits (quality-adjusted life-years, 7.77 versus 6.48), and had a 100% probability of being cost-effective. Both deterministic sensitivity analysis and probabilistic sensitivity analyses yielded similar results. CONCLUSIONS: Both within-trial and long-term economic analyses showed that tenecteplase was highly likely to be cost-effective for patients with acute stroke before thrombectomy. Recommending the use of tenecteplase over alteplase could lead to a cost saving to the healthcare system both in the short and long term. Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT02388061.

Cost-effectiveness of stent-retriever thrombectomy in large vessel occlusion strokes of the anterior circulation: Analysis from the French societal perspective.

OBJECTIVES: To determine the cost-effectiveness of stent retriever thrombectomy (SRT) added to standard of care (SOC) in large vessel occlusion (LVO) strokes, adopting the French societal perspective given the lack of published studies with such perspective. METHODS: We developed an hybrid model (decision tree until one year post-stroke followed by a Markov model from one year onward). The time horizon was 20 years. We calculated transition probabilities across the modified Rankin Scale (mRS) based on a published meta-analysis. The main outcome measure was quality adjusted life-years (QALYs) gained. Resources and input costs were derived from a literature search. We calculated the incremental cost-effectiveness ratio (ICER) expressed as cost/QALY. We used 1-way deterministic and probabilistic sensitivity analysis (PSA) to evaluate the model uncertainty. RESULTS: In the base-case, adding SRT to SOC resulted in increased effectiveness of 0.73 QALY while total costs were reduced by 3,874€ (ICER of -5,400€/QALY). In the scenario analysis adopting the French healthcare system perspective, the ICER was 4,901€/QALY. Parameters the most influential were the relative risks of SRT over SOC for 90-days mortality and for 90-days mRS 0-2, and the time horizon. PSA showed the 95% confidence interval of the ICER was -21,324 to 4,591€/QALY, with SRT having 85.5% chance to be dominant and 100% to be cost-effective at a threshold of 50,000€/QALY. CONCLUSION: SRT was dominant from a French societal perspective, from 9 years post-stroke onwards. Cost-effectiveness of SRT added to SOC becomes undisputable with evidences from payer and societal viewpoints.

Fast-track thrombolysis protocol: A single-session approach for acute iliofemoral deep venous thrombosis.

OBJECTIVE: Catheter-directed thrombolysis in the treatment of acute iliofemoral deep venous thrombosis (IFDVT) often requires more than one interventional session to yield successful outcomes. Catheter-directed thrombolysis is generally expensive, requiring prolonged hospital stay that may be associated with increased local and systemic hemorrhagic complications. We developed the fast-track thrombolysis protocol (FTTP) to address these issues. The goal of FTTP is to restore patency during the initial session of thrombolysis, thereby minimizing costs and complications associated with prolonged thrombolysis. METHODS: A retrospective analysis of 38 patients treated for acute IFDVT using FTTP at our institution from January 2014 to February 2019 was performed. The protocol includes periadventitial injection of lidocaine at the venipuncture site under ultrasound guidance, contrast venography of the entire target segment, pharmacomechanical rheolytic thrombectomy of the occluded venous segment, tissue plasminogen activator infusion along the occluded segment, balloon maceration of the thrombus, and, if indicated, venous stent placement in areas of significant (≥50%) stenosis refractory to thrombolysis and balloon angioplasty. Once the thrombus was cleared, patients were prescribed oral antithrombotic therapy. RESULTS: Thirty-eight primary FTTPs (45 total interventions) were performed in 38 patients. The median age was 66 years (range, 39-93 years); 60.5% were female. Initial venous access was most often obtained through the popliteal vein, followed by the femoral and great saphenous veins. The mean operative time was 122 minutes (range, 59-249 minutes), and the median volume of tissue plasminogen activator infused was 10 mg (range, 4-20 mg). The median cost per procedure, including devices and medication, was $5374.45. Median postoperative length of stay was 1 day (range, 1-45 days). Successful single-session FTTP, as determined by completion venography, was accomplished in 81.5% (n = 31/38) of cases. The remaining seven cases (18.5%) required one additional session. Of the 38 patients, 30 (79%) required iliac vein stenting. Periprocedural complications consisted of one patient with retroperitoneal hemorrhage that was managed conservatively. No patients experienced rethrombosis within 30 days of FTTP. During the 5-year study period, there were no cases of pulmonary embolism, significant local or systemic hemorrhage, limb loss, or mortality. CONCLUSIONS: FTTP, as presented herein, appears to be a safe, effective, and cost-effective technique in the resolution of acute IFDVT.

Cost-effectiveness of intrapleural use of tissue plasminogen activator and DNase in pleural infection: evidence from the MIST2 randomised controlled trial.

The MIST2 (Second Multicentre Intrapleural Sepsis Trial) trial showed that combined intrapleural use of tissue plasminogen activator (t-PA) and recombinant human DNase was effective when compared with single agents or placebo. However, the treatment costs are significant and overall cost-effectiveness of combined therapy remains unclear.An economic evaluation of the MIST2 trial was performed to assess the cost-effectiveness of combined therapy. Costs included were those related to study medications, initial hospital stay and subsequent hospitalisations. Outcomes were measured in terms of life-years gained. All costs were reported in euro and in 2016 prices.Mean annual costs were lowest in the t-PA-DNase group (EUR 10 605 for t-PA, EUR 17 856 for DNase, EUR 13 483 for placebo and EUR 7248 for t-PA-DNase; p=0.209). Mean 1-year life expectancy was 0.988 for t-PA, 0.923 for DNase, and 0.969 for both placebo and t-PA-DNase (p=0.296). Both DNase and placebo were less effective, in terms of life-years gained, and more costly than t-PA. When placebo was compared with t-PA-DNase, the incremental cost per life-year gained of placebo was EUR 1.6 billion, with a probability of 0.85 of t-PA-DNase being cost-effective.This study demonstrates that combined t-PA-DNase is likely to be highly cost-effective. In light of this evidence, a definitive trial designed to facilitate a thorough economic evaluation is warranted to provide further evidence on the cost-effectiveness of this promising combined intervention.

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.

Tissue plasminogen activator vs heparin for locking central venous catheters between apheresis procedures.

BACKGROUND: Central venous catheters (CVCs) for apheresis procedures require regular locking/flushes to maintain adequate flow rates. Literature comparing locking solutions for apheresis, where the time interval between procedures can be longer than for hemodialysis (many days to weeks), is lacking. In this study, catheter malfunction rates using recombinant tissue plasminogen activator (rt-PA) vs heparin for locking CVC between apheresis procedures were compared. STUDY DESIGN AND METHODS: A retrospective review of 93 extracorporeal photopheresis procedures in 10 patients was performed at our institution. About 1000 U/mL heparin or 2 mg rt-PA was used as the locking solution. Heparin locks were changed at least once per week and rt-PA locks could be left in place for up to 4 weeks. Following these locks, inadequate blood flow noted on accessing CVC and/or during the procedure was scored on as: no issues, some issues, or significant issues. Binary logistic regression was used to evaluate for potential statistical difference in outcomes. Cost analysis was also performed. RESULTS: No statistically significant difference was noted in outcomes between heparin and rt-PA lock (P value = 0.15). Total cost of heparin lock administration ($91-$362.50) was found to be more than rt-PA lock ($76) when more than one flush was needed between procedures. CONCLUSIONS: For apheresis use, rt-PA and heparin CVC locks seem to have similar outcomes in preventing CVC malfunction. The convenience of not needing any flushes between procedures and overall cost of administering fewer locks favors rt-PA use when the interval between procedures is >7 days.

Cost-effectiveness analysis of mechanical thrombectomy plus tissue-type plasminogen activator compared with tissue-type plasminogen activator alone for acute ischemic stroke in France.

BACKGROUND AND PURPOSE: Recent studies demonstrated the benefit of mechanical thrombectomy (MT) plus intravenous tissue-type plasminogen activator (IV-tPA) (MT-IV-tPA) in acute ischemic stroke. This study aimed to estimate the cost-utility of MT-IV-tPA compared with IV-tPA alone from the perspective of the French National Health Insurance. METHODS: We developed a decision tree for the first 3 months after stroke onset and a Markov model until 10 years post-stroke. The health states of the Markov model were according to the modified Rankin Scale (mRS): independent (mRS=0-2), dependent (mRS=3-5), dead (mRS=6). Recurrent stroke was the fourth health stage of our model. We conducted systematic literature reviews and meta-analyses to estimate the cost and utility of each health state, and the transition probabilities between health states. A microcosting study was conducted to estimate the cost of MT. We estimated the incremental cost-effectiveness ratio of MT-IV-tPA and conducted a probabilistic analysis in order to estimate the probability that MT-IV-tPA is cost-effective compared to IV-tPA, the expected value of perfect information (EVPI), and the expected value of partial perfect information (EVPPI), given the uncertainty surrounding the value of our model's parameters. RESULTS: The total mean (standard deviation (SD) cost of MT was €6708.9 (2357.0). The incremental cost-effectiveness ratio (ICER) of the strategy using IV-tPA combined to MT costs was €14,715 per QALY gained as compared to a strategy using IV-tPA alone. The probabilistic analysis showed that the probability of MT-IV-TPA being cost-effective was 85.4% at threshold willingness-to-pay of €30,000 per QALY gained, reaching 98% at €50,000 per QALY gained. CONCLUSION: Although there is no universally accepted willingness-to-pay threshold in France, our analysis suggest that MT combined to IV-tPA can be considered a cost-effective treatment compared with IV-tPA alone.

Pharmacoeconomic impact of an alternative workflow process for stroke.

OBJECTIVE: The objective of this study was to evaluate a new multidisciplinary process in which intravenous alteplase (tPA) waste, used for acute ischemic stroke (AIS), was salvaged in an attempt to maximize cost effectiveness without impacting door-to-needle (DTN) administration times. DESIGN: This was a retrospective cohort between May 2017 and February 2018. The primary endpoint evaluated for this study was the total tPA salvaged and total cost savings in U.S. dollars. Secondary endpoints evaluated included overall DTN time in minutes. SETTING: Emergency department of a primary stroke center. PATIENTS: A convenience sample of sequential adult (>18 years) patients who received tPA in the ED for AIS were included for analysis. INTERVENTIONS: New stroke process which involved bedside mixing of tPA and salvaging of excess waste in the main central pharmacy. MEASUREMENTS AND MAIN RESULTS: A total of 50 patients were included in the final analysis. There were 25 patients included in the new process and old process groups respectively. A total of 605 mg of alteplase was salvaged from 25 patients in the new process group which was associated with an estimated cost savings of over $120,000 annually. Patients in the new process group had statistically faster average (52 min vs. 60 min; p = 0.01) and median (50 min vs. 58 min; p = 0.03) DTN administration times. CONCLUSION: Preliminary data, in this pilot study, utilizing a multidisciplinary model for tPA administration led to significant cost savings of tPA and decreases in overall DTN administration times.

Regional Intervention of Stroke Care to Increase Thrombolytic Therapy for Acute Ischemic Stroke.

Background and Purpose- The aims of this study were to investigate the effect of an intervention to unblind data on r-tPA (recombinant tissue-type plasminogen activator) administration and sharing data with chief executive officers of participating hospitals, on r-tPA administration rates postintervention and on potential healthcare cost savings implemented at 26 Southeast Texas Regional Advisory Council hospitals. Methods- Retrospective analysis of prospective data on thrombolytic therapy from 26 Southeast Texas Regional Advisory Council hospitals, collected between April 2014 and June 2016. The control (blinded) period (Q2-2014 to Q2-2015) was followed by unblinding (Q3-2015). Results- Intervention was associated with 21.1% increase in r-tPA administration rates, with 38.5% increase in r-tPA administration with door-to-needle time ≤60 minutes. An absolute increase in r-tPA administration of 2.1% was seen with an average lifetime cost savings of $3.6 million. Conclusions- Transparent regional data sharing was associated with improved r-tPA administration and healthcare cost savings.

Cost-effectiveness analysis of mechanical thrombectomy with stent retriever in the treatment of acute ischemic stroke in Italy.

BACKGROUND: Stroke has a significant disease burden in terms of acute and long-term disability in Italy and throughout the world. Endovascular treatments for the management of a stroke event have been coupled in the past years with the possibility to mechanically remove the occlusion by means of specially designed thrombectomy devices, and their exclusive use showed levels of effectiveness in line with those of the existing pharmacological treatments. OBJECTIVE: To assess the cost-effectiveness of mechanical thrombectomy (MT) with the Solitaire Revascularization Device (stent retriever) for the treatment of acute ischemic stroke (AIS) in patients with large vessel occlusions (LVOs), comparing MT plus intravenous tissue plasminogen activation (MT plus IV t-PA) vs IV t-PA alone, in Italy. METHODS: A Markov model was used to simulate costs and benefits of MT plus IV t-PA and IV t-PA alone over a 5-year time horizon and considering the perspective of the Italian National Health Service (NHS). Results are reported in terms of Incremental Cost Effectiveness Ratio (ICER). Deterministic and probabilistic sensitivity analyses are carried out in order to test the robustness of the results. RESULTS: Total costs of MT plus IV t-PA and IV t-PA alone are equal to €31,798 and €34,855, respectively. The MT allows incremental QALYs for 0.77, determining a dominant ICER. The utilities associated to the mRS health states are the parameters with the highest impact on the results. Multiway sensitivity analyses determined a 90% probability of dominance. CONCLUSIONS: MT plus IV t-PA for AIS patients with LVO is cost-effective from year 1 through year 3, and cost-saving from year 4 onward in the Italian context, achieving better results, both in terms of efficacy and in terms of resource consumption.

A literature-based cost analysis of tissue plasminogen activator for prevention of biliary stricture in donation after circulatory death liver transplantation.

INTRODUCTION: This study sought to approximate the cost-effectiveness of tPA utilization for prevention of biliary strictures (PTBS) in donation after circulatory death liver transplantation (DCD-LT). METHODS: Previously-reported PTBS rates in DCD-LT with and without tPA were used to calculate the number needed to treat (NNT) for prevention of one PTBS. The incremental cost of PTBS was then used to determine the cost effectiveness of tPA for prevention of PTBS. RESULTS: The incidence of PTBS in the setting of tPA administration was 20%, while incidence in patients without tPA use was 43% (p < 0.001). Meta-analysis demonstrated a risk reduction of 15.7%, which translated into a NNT of 6.4. Cost associated with treating 6.4 patients was $50,353. Based on an incremental cost of $81,888 associated with PTBS management, use of tPA in DCD-LT protocols was estimated to save $31,528 per PTBS prevented. CONCLUSION: Utilization of tPA in DCD-LT protocols represents one possible cost-effective strategy for prevention of PTBS in DCD-LT.

Catheter-Directed Thrombolysis Versus Pharmacomechanical Thrombectomy for Upper Extremity Deep Venous Thrombosis: A Cost-Effectiveness Analysis.

BACKGROUND: Upper extremity deep vein thrombosis represents (UEDVT) 2-3% of all deep vein thrombosis. Catheter directed thrombolysis (CDT) was replaced largely by pharmacomechanical thrombolysis (PMT) in our institution. In this study we compared the immediate and 1-year results as well as the total hospital costs between CDT and PMT in the treatment of UEDVT. METHODS: From 2006 to 2013, 55 patients with UEDVT were treated with either CDT or PMT at Helsinki University Hospital. Of them, 43 underwent thoracoscopic rib resection later to relieve phlebography-confirmed vein compression. This patient cohort was prospectively followed up with repeated phlebographies. CDT was performed to 24 patients, and 19 had PMT with a Trellis™ device. Clinical evaluation and vein patency assessment were performed with either phlebography or ultrasound 1 year after the thrombolysis. Primary outcomes were immediate technical success, 1-year vein patency, and costs of the initial treatment. RESULTS: The immediate overall technical success rate, defined as recanalization of the occluded vein and removal of the fresh thrombus, was 91.7% in the CDT group and 100% in the PMT group (n.s.). The median thrombolytic time was significantly longer in CDT patients than that in PMT patients (21.1 vs. 0.33 hr, P < 0.00001). There were no procedure-related complications. The 1-year primary assisted patency rate was similar in both the groups (91.7% and 94.7%). There were no recurrences of clinical DVT. The hospital costs for the acute period were significantly lower in the PMT group than those in the CDT group (medians: 11,476 € and 5,975 € in the CDT and PMT groups, respectively [P < 0.00001]). CONCLUSIONS: The clinical results of the treatment of UEDVT with CDT or PMT were similar. However, PMT required shorter hospital stay and less intensive surveillance, leading to lower total costs.

Intravenous thrombolysis before endovascular therapy for large vessel strokes can lead to significantly higher hospital costs without improving outcomes.

BACKGROUND: Limited efficacy of IV recombinant tissue plasminogen activator (rt-PA) for large vessel occlusions (LVO) raises doubts about its utility prior to endovascular therapy. PURPOSE: To compare outcomes and hospital costs for anterior circulation LVOs (middle cerebral artery, internal carotid artery terminus (ICA-T)) treated with either primary endovascular therapy alone (EV-Only) or bridging therapy (IV+EV)). METHODS: A single-center retrospective analysis was performed. Clinical and demographic data were collected prospectively and relevant cost data were obtained for each patient in the study. RESULTS: 90 consecutive patients were divided into EV-Only (n=52) and IV+EV (n=38) groups. There was no difference in demographics, stroke severity, or clot distribution. The mean (SD) time to presentation was 5:19 (4:30) hours in the EV-Only group and 1:46 (0:52) hours in the IV+EV group (p<0.0001). Recanalization: EV-Only 35 (67%) versus IV+EV 31 (81.6%) (p=0.12). Favorable outcome: EV-Only 26 (50%) versus IV+EV 22 (58%) (p=0.45). For patients presenting within 4.5 hours (n=64): Recanalization: EV-Only 21/26 (81%) versus IV+EV 31/38 (81.6%) (p=0.93). Favorable outcome: EV-Only 14/26 (54%) versus IV+EV 22/38 (58%) (p=0.75). There was no significant difference in rates of hemorrhage, mortality, home discharge, or length of stay. A stent retriever was used in 67 cases (74.4%), with similar recanalization, outcomes, and number of passes in the EV-Only and IV+EV groups. The mean (SD) total hospital cost was $33 810 (13 505) for the EV-Only group and $40 743 (17 177) for the IV+EV group (p=0.02). The direct cost was $23 034 (8786) for the EV-Only group and $28 711 (11 406) for the IV+EV group (p=0.007). These significantly higher costs persisted for the subgroup presenting in <4.5 hours and the stent retriever subgroup. IV rt-PA administration independently predicted higher hospital costs. CONCLUSIONS: IV rt-PA did not improve recanalization, thrombectomy efficacy, functional outcomes, or length of stay. Combined therapy was associated with significantly higher total and direct hospital costs than endovascular therapy alone.

Cost-effectiveness analysis of tissue plasminogen activator in acute ischemic stroke in Iran.

AIMS: Tissue plasminogen activator (tPA) is used to treat acute ischemic stroke up to 4.5 h after symptom onset. Its cost-effectiveness in developing countries is not specified yet. This study aimed to study cost-effectiveness of tPA in Iran. METHODS: This is a cost-effectiveness analysis from the perspective of the third party payer to compare IV tPA with no tPA of ischemic stroke. A Markov model with a lifetime horizon was used to analyze the costs and outcomes. Cost data were extracted from the 94 patients admitted in two hospitals in Iran. All costs were calculated based on US dollars in 2016. Quality-adjusted life years (QALY) were extracted from previously published literature. Cost-effectiveness was determined by calculating ICER by TreeAge Pro 2011 software. RESULTS: Lifetime costs of no tPA strategy were higher than tPA ($10,718 in the no tPA group compared with $8,796 in the tPA group). The tPA arm gained 0.20 QALY compared with no tPA. ICER was $8,471 per QALY. ICER value suggests that tPA is cost-effective compared with no tPA. LIMITATIONS: The limitations of the present study are the reliance on calculated QALY value of other countries and difficulty in accessing patients treated with tPA. CONCLUSIONS: The balance of hospitalization and rehabilitation costs and QALYs support the conclusion that treatment with intravenous tPA in the 4.5-h time window is cost-effective from the perspectives of the third party payer and inclusion of tPA in the insurance benefit package being reasonable.

Age-specific Cost Effectiveness of Using Intravenous Recombinant Tissue Plasminogen Activator for Treating Acute Ischemic Stroke.

INTRODUCTION: Studies have demonstrated that intravenous recombinant tissue plasminogen activator (IV rtPA) is a cost-effective treatment for acute ischemic stroke. Age-specific cost effectiveness has not been well examined. This study estimated age-specific incremental cost-effectiveness ratios (ICERs) of IV rtPA treatment versus no IV rtPA. METHODS: A Markov model was developed to examine the economic impact of IV rtPA over a 20-year time horizon on four age groups (18-44, 45-64, 65-80, and ≥81 years) from the U.S. healthcare sector perspective. The model used health outcomes from a national stroke registry adjusted by parameters from previous literature and current hospitalization costs in 2013 U.S. dollars. Long-term annual costs and quality-adjusted life years (QALYs) in the years after a stroke were discounted at 3% per year. Incremental costs, incremental QALYs, and ICERs were estimated and sensitivity analyses were conducted between 2015 and 2017. RESULTS: Use of IV rtPA gained 0.55 QALYs and cost $3,941 more than no IV rtPA for stroke patients aged ≥18 years over a 20-year time horizon. IV rtPA was a dominant strategy compared to no IV rtPA for patients aged 18-44 and 45-64 years. For patients aged 65-80 years, IV rtPA gained 0.44 QALYs and cost $4,872 more than no IV rtPA (ICER=$11,132/QALY). For patients aged ≥81 years, ICER was estimated at $48,676/QALY. CONCLUSIONS: IV rtPA saved costs and improved health outcomes for patients aged 18-64 years and was cost effective for those aged ≥65 years. These findings support the use of IV rtPA.

Cost-Effectiveness of Thrombectomy in Patients With Acute Ischemic Stroke: The THRACE Randomized Controlled Trial.

BACKGROUND AND PURPOSE: The benefit of mechanical thrombectomy added to intravenous thrombolysis (IVT) in patients with acute ischemic stroke has been largely demonstrated. However, evidence of the economic incentive of this strategy is still limited, especially in the context of a randomized controlled trial. We aimed to analyze whether mechanical thrombectomy combined with IVT (IVMT) is cost-effective when compared with IVT alone. METHODS: Individual-level cost and outcome data were collected in the THRACE randomized controlled trial (Thrombectomie des Artères Cerébrales) including patients with acute ischemic stroke. Patients were assigned to receive IVT or IVMT. The primary outcomes were modified Rankin Scale score of functional independence at 90 days (score 0-2) and the EuroQol-5D quality-of-life score at 1 year. RESULTS: Treating acute ischemic stroke with IVMT (n=200) versus IVT (n=202) increased the rate of functional independence by 10.9% (53.0% versus 42.1%; P=0.028), at an increased cost of $2116 (€1909), with no significant difference in mortality (12% versus 13%; P=0.70) or symptomatic intracranial hemorrhage (2% versus 2%; P=0.71). The cost per one averted case of disability was estimated at $19 379 (€17 480). The incremental cost per one quality-adjusted life year gained was $14 881 (€13 423). On sensitivity analysis, the probability of cost-effectiveness with IVMT was 84.1% in terms of cases of averted disability and 92.2% in terms of quality-adjusted life years. CONCLUSIONS: Based on randomized trial data, this study demonstrates that IVMT used to treat acute ischemic stroke is cost-effective when compared with IVT alone. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT01062698.