[Cost-utility analysis: Mechanical thrombectomy plus thrombolysis in ischemic stroke due to large vessel occlusion in the public sector in Chile]. / Análisis de costo utilidad: trombectomía mecánica más trombólisis en accidente vascular cerebral isquémico debido a oclusión de grandes vasos en el sector público en Chile.

INTRODUCTION: Several studies demonstrate the therapeutic superiority of thrombolysis plus mechanical thrombectomy versus thrombolysis alone to treat stroke. OBJECTIVE: To analyze the cost-utility of thrombolysis plus mechanical thrombectomy versus thrombolysis in patients with ischemic stroke due to large vessel occlusion. METHODS: Cost-utility analysis. The model used is blended: Decision Tree (first 90 days) and Markov in the long term, of seven health states based on a disease-specific scale, from the Chilean public insurance and societal perspective. Quality-Adjusted Life-Years and costs are evaluated. Deterministic (DSA) and probabilistic (PSA) analyses were carried out. RESULTS: From the public insurance perspective, in the base case, mechanical thrombectomy is associated with lower costs in a lifetime horizon, and with higher benefits (2.63 incremental QALYs, and 1.19 discounted incremental life years), at a Net Monetary Benefit (NMB) of CLP 37,289,874, and an Incremental Cost-Utility Ratio (ICUR) of CLP 3,807,413/QALY. For the scenario that incorporates access to rehabilitation, 2.54 incremental QALYs and 1.13 discounted life years were estimated, resulting in an NMB of CLP 35,670,319 and ICUR of CLP 3,960,624/QALY. In the scenario that incorporates access to long-term care from a societal perspective, the ICUR falls to CLP 951,911/QALY, and the NMB raises to CLP 43,318,072, improving the previous scenarios. In the DSA, health states, starting age, and relative risk of dying were the variables with the greatest influence. The PSA for the base case corroborated the estimates. CONCLUSIONS: Thrombolysis plus mechanical thrombectomy adds quality of life at costs acceptable for decision-makers versus thrombolysis alone. The results are consistent with international studies.

INTRODUCCIÓN: Diversos estudios demuestran la superioridad terapéutica de la trombólisis más trombectomía mecánica, versus trombólisis sola, en el tratamiento del accidente vascular cerebral. OBJETIVOS: Analizar el costo utilidad de la trombólisis más trombectomía versus trombólisis sola en pacientes con accidente vascular cerebral isquémico con oclusión de grandes vasos. MÉTODOS: Evaluación de costo utilidad. Se ha utilizado un modelo mixto: árbol de decisión (primeros 90 días) y Markov en el largo plazo, de siete estados de salud definidos en escala específica de enfermedad, desde la perspectiva del seguro público chileno y societal. Se evalúan costos y años de vida ajustados por calidad. Se realizó análisis de incertidumbre determinístico y probabilístico. RESULTADOS: Bajo la perspectiva de seguro público, en el caso base la trombectomía mecánica se relaciona con menores costos en un horizonte de por vida, con mayores beneficios (2,63 años de vida ajustados por calidad incrementales, y 1,19 años de vida incrementales descontados), a un beneficio monetario neto de $37 289 874 pesos chilenos, y una razón incremental de costo utilidad de $3 807 413 pesos por años de vida ajustados por calidad. Para el escenario que agrega acceso a rehabilitación se estimaron 2,54 años de vida ajustados por calidad incremental y 1,13 años de vida descontados, resultando en un beneficio monetario neto de $35 670 319 pesos y razón incremental de costo utilidad de $3 960 624 pesos por años de vida ajustados por calidad. En el escenario que agrega el efecto de acceso a cuidados de larga duración con perspectiva societal, la razón incremental de costo utilidad cae hasta $951 911 pesos por años de vida ajustados por calidad y el beneficio monetario neto se eleva a $43 318 072 pesos, superando las estimaciones anteriores. En el análisis de incertidumbre determinístico, los estados de salud, edad de inicio de la cohorte y riesgo relativo de morir, fueron las variables con mayor influencia. El análisis de incertidumbre probabilístico para el caso base, corroboró las estimaciones. CONCLUSIONES: La trombólisis más trombectomía mecánica agrega calidad de vida a costos aceptables por el tomador de decisión, versus trombólisis sola. Los resultados son consistentes con los estudios internacionales.

The effect of catheter-directed thrombolytic use on readmission rates and in-hospital outcomes among cancer patients with venous thromboembolism in the United States.

BACKGROUND: Cancer inducing a hypercoagulable state, venous thromboembolism (VTE) remains a leading cause of morbidity and mortality globally. We assessed the impacts of cancer on the likelihood for readmission after a VTE-targeted procedure. METHODS: We created a new cohort using discharge-level data from all hospitalizations from State Inpatient Databases of geographically dispersed participating states (18-27 states). RESULTS: In those presenting with VTE during index-admission (619 241), 2.4% patients underwent catheter directed thrombolytic therapy (CDL) on index admission and among those 20.3% had cancer. Moreover, the 30-day readmission rate amongst CDL recipients (10 776 overall) was 14.3% in those with cancer compared to 8.8% in those with no cancer history (P < .0001). Additionally, in-hospital mortality (5.7% vs 1.1%; P = 0.009) and cost-of-care ($11 014 ± 914 vs $10 520 ± 534; P = .04) was significantly higher in cancer compared to noncancer. CONCLUSION: The use of CDL does not appear to reduce the risk of returning for a VTE-related admission in cancer.

Assessment of Anticoagulation in Patients Receiving Ultrasound-Assisted Catheter-Directed Thrombolysis for Treatment of Pulmonary Embolism.

BACKGROUND: Ultrasound-assisted, catheter-directed thrombolysis (USAT) has emerged as a popular treatment option for submassive pulmonary embolism (PE). The optimal strategy for transitioning patients from full-intensity to reduced-intensity heparin during the procedure has yet to be established. OBJECTIVE: The goal of this study was to evaluate the anticoagulation management in patients receiving catheter-directed thrombolysis with USAT. METHODS: A retrospective chart review was conducted of patients who received USAT for the treatment of PE. Institutional review board approval was obtained. The primary objective was to determine the proportion of patients with a therapeutic activated partial thromboplastin time (aPTT) prior to and during tissue-plasminogen activator (tPA) infusion. Secondary outcomes included heparin requirements, the rate of bleeding complications, and the appropriateness of long-term venous thromboembolism management. RESULTS: A therapeutic aPTT value was achieved in 32 patients (54.2%) prior to USAT and 35 patients (59.3%) during tPA infusion. Heparin requirements were reduced from 15.1 ± 4.1 to 12.8 ± 4.2 U/kg/h for patients who achieved a therapeutic aPTT both prior to and during tPA infusion. Bleeding occurred in 34.4% of patients and tended to be minimal (20.3%) or minor (10.9%). The majority of patients were discharged on a direct oral anticoagulant (63%), followed by warfarin (32%) and enoxaparin (5%). Conclusion and Relevance: To our knowledge, this is the first study that has assessed heparin management in the setting of USAT. The results of these data may aid in empirically dose adjusting unfractionated heparin to ensure safe and effective anticoagulation for patients receiving USAT.

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.

Mechanical Thrombectomy in Patients With Acute Ischemic Stroke: A Health Technology Assessment.

BACKGROUND: In Ontario, current treatment for eligible patients who have an acute ischemic stroke is intravenous thrombolysis (IVT). However, there are some limitations and contraindications to IVT, and outcomes may not be favourable for patients with stroke caused by a proximal intracranial occlusion. An alternative is mechanical thrombectomy with newer devices, and a number of recent studies have suggested that this treatment is more effective for improving functional independence and clinical outcomes. The objective of this health technology assessment was to evaluate the clinical effectiveness and cost-effectiveness of new-generation mechanical thrombectomy devices (with or without IVT) compared to IVT alone (if eligible) in patients with acute ischemic stroke. METHODS: We conducted a systematic review of the literature, limited to randomized controlled trials that examined the effectiveness of mechanical thrombectomy using stent retrievers and thromboaspiration devices for patients with acute ischemic stroke. We assessed the quality of the evidence using the GRADE approach. We developed a Markov decision-analytic model to assess the cost-effectiveness of mechanical thrombectomy (with or without IVT) versus IVT alone (if eligible), calculated incremental cost-effectiveness ratios using a 5-year time horizon, and conducted sensitivity analyses to examine the robustness of the estimates. RESULTS: There was a substantial, statistically significant difference in rate of functional independence (GRADE: high quality) between those who received mechanical thrombectomy (with or without IVT) and IVT alone (odds ratio [OR] 2.39, 95% confidence interval [CI] 1.88-3.04). We did not observe a difference in mortality (GRADE: moderate quality) (OR 0.80, 95% CI 0.60-1.07) or symptomatic intracerebral hemorrhage (GRADE: moderate quality) (OR 1.11, 95% CI 0.66-1.87). In the base-case cost-utility analysis, which had a 5 year time horizon, the costs and effectiveness for mechanical thrombectomy were $126,939 and 1.484 quality-adjusted life-years (QALYs) (2.969 life-years). The costs and effectiveness for IVT alone were $124,419 and 1.273 QALYs (2.861 life-years), respectively. Mechanical thrombectomy was associated with an incremental cost-effectiveness ratio of $11,990 per QALY gained. Probabilistic sensitivity analysis showed that the probability of mechanical thrombectomy being cost-effective was 57.5%, 89.7%, and 99.6%, at thresholds of $20,000, $50,000, and $100,000 per QALY gained, respectively. We estimated that adopting mechanical thrombectomy would lead to a cost increase of approximately $1 to 2 million. CONCLUSIONS: High quality evidence showed that mechanical thrombectomy significantly improved functional independence and appeared to be cost-effective compared to IVT alone for patients with acute ischemic stroke.

Endovascular Treatment of Acute Stroke: Evolution and Selection of Techniques and Instruments Based on Thrombus Imaging.

Mechanical thrombectomy provides higher recanalization rates than intravenous or intra-arterial thrombolysis. Finally this has been shown to translate into improved clinical outcome in six multicentric randomized controlled trials. However, within cohorts the clinical outcomes may vary, depending on the endovascular techniques applied. Systems aiming mainly for thrombus fragmentation and lacking a protection against distal embolization have shown disappointing results when compared to recent stent-retriever studies or even to historical data on local arterial fibrinolysis. Procedure-related embolic events are usually graded as adverse events in interventional neuroradiology. In stroke, however, the clinical consequences of secondary emboli have so far mostly been neglected and attributed to progression of the stroke itself. We summarize the evolution of instruments and techniques for endovascular, image-guided, microneurosurgical recanalization in acute stroke, and discuss how to avoid procedure-related embolic complications.

Comparison of endovascular treatment approaches for acute ischemic stroke: cost effectiveness, technical success, and clinical outcomes.

INTRODUCTION: The use of mechanical thrombectomy for the treatment of acute ischemic stroke has significantly advanced over the last 5 years. Few data are available comparing the cost and clinical and angiographic outcomes associated with available techniques. The aim of this study is to compare the cost and efficacy of current endovascular stroke therapies. METHODS: A single-center retrospective review was performed of the medical record and hospital financial database of all ischemic stroke cases admitted from 2009 to 2013. Three discrete treatment methodologies used during this time were compared: traditional Penumbra System (PS), stent retriever with local aspiration (SRLA) and A Direct Aspiration first Pass Technique (ADAPT). Statistical analyses of clinical and angiographic outcomes and costs for each group were performed. RESULTS: 222 patients (45% men) underwent mechanical thrombectomy. Successful revascularization was defined as Thrombolysis In Cerebral Infarction (TICI) 2b/3 flow, which was achieved in 79% of cases with PS, 83% of cases with SRLA, and 95% of cases with ADAPT. The average total cost of hospitalization for patients was $51,599 with PS, $54,700 with SRLA, and $33 ,11 with ADAPT (p<0.0001). Average times to recanalization were 88 min with PS, 47 min with SRLA, and 37 min with ADAPT (p<0.0001). Similar rates of good functional outcomes were seen in the three groups (PS 36% vs SRLA 43% vs ADAPT 47%; p=0.4). CONCLUSIONS: The ADAPT technique represents the most technically successful yet cost-effective approach to revascularization of large vessel intracranial occlusions.

Time to angiographic reperfusion in acute ischemic stroke: decision analysis.

BACKGROUND AND PURPOSE: Our objective was to use decision analytic modeling to compare 2 treatment strategies of intravenous recombinant tissue-type plasminogen activator (r-tPA) alone versus combined intravenous r-tPA/endovascular therapy in a subgroup of patients with large vessel (internal carotid artery terminus, M1, and M2) occlusion based on varying times to angiographic reperfusion and varying rates of reperfusion. METHODS: We developed a decision model using Interventional Management of Stroke (IMS) III trial data and comprehensive literature review. We performed 1-way sensitivity analyses for time to reperfusion and 2-way sensitivity for time to reperfusion and rate of reperfusion success. We also performed probabilistic sensitivity analyses to address uncertainty in total time to reperfusion for the endovascular approach. RESULTS: In the base case, endovascular approach yielded a higher expected utility (6.38 quality-adjusted life years) than the intravenous-only arm (5.42 quality-adjusted life years). One-way sensitivity analyses demonstrated superiority of endovascular treatment to intravenous-only arm unless time to reperfusion exceeded 347 minutes. Two-way sensitivity analysis demonstrated that endovascular treatment was preferred when probability of reperfusion is high and time to reperfusion is small. Probabilistic sensitivity results demonstrated an average gain for endovascular therapy of 0.76 quality-adjusted life years (SD 0.82) compared with the intravenous-only approach. CONCLUSIONS: In our post hoc model with its underlying limitations, endovascular therapy after intravenous r-tPA is the preferred treatment as compared with intravenous r-tPA alone. However, if time to reperfusion exceeds 347 minutes, intravenous r-tPA alone is the recommended strategy. This warrants validation in a randomized, prospective trial among patients with large vessel occlusions.

Contrast-enhanced sonothrombolysis in a porcine model of acute peripheral arterial thrombosis and prevention of anaphylactic shock.

Acute peripheral arterial thrombosis can be threatening to life and limb. Dissolution of the thrombus local catheter-directed intra-arterial infusion of fibrinolytic agents such as urokinase is the standard therapy for thrombosis; however, this method is time-intensive, and amputation of the affected limb is still needed in 10-30% of cases. Furthermore, thrombolytic therapy carries the risk of bleeding complications. The use of small gas-filled bubbles, or ultrasound contrast agents (UCAs), in combination with ultrasound has been investigated as an improved thrombolytic therapy in acute coronary and cerebral arterial thrombosis. The authors describe a porcine model of acute peripheral arterial occlusion to test contrast-enhanced sonothrombolysis approaches that combine ultrasound, UCAs and fibrinolytic agents and recommend a strategy for preventing severe allergic reactions to UCAs in the pigs.

In-room assessment of cerebral blood volume for guidance during intra-arterial thrombolytic therapy.

In acute ischemic stroke, the ability to estimate the penumbra and infarction core ratio helps to triage those who will potentially benefit from thrombolytic therapies. Flat-panel post-contrast DynaCT imaging can provide both vasculature and parenchymal blood volume within the angio room to monitor hemodynamic changes during the endovascular procedures. We report on an 80-year-old woman who suffered from an acute occlusion of the right distal cervical internal carotid artery. She was transferred to the angio room where in-room post-contrast flat-panel DynaCT imaging (syngo Neuro PBV IR) was performed to access the ischemic tissue, followed by successful mechanical thrombolytic therapy.