Hospitalization period and direct medical cost in patients using warfarin or novel oral anti-coagulants after a cerebral embolism.

Background Warfarin has been used in Japan for a long time in patients after cerebral embolism to prevent recurrence. Recently, several novel oral anti-coagulants (NOACs) have been approved for use and are gradually replacing warfarin. However, it remains unclear whether warfarin and other NOACs differ from each other with respect to drug costs and length of stay (LOS) during treatment in Japan. Objective To assess differences in LOS and direct medical cost between patients after cerebral embolism treated with warfarin and those treated with NOACs. Setting Thirteen acute care hospitals in Japan. Method For hospitalized patients with cerebral embolisms who were treated with NOACs and/or warfarin between April 2012 and March 2014, we assessed LOS for patients with warfarin and NOAC using log-rank test, and stratified proportional hazard regression. Also, we assess direct medical cost using paired-t test. Main Outcome measure LOS and medical cost after first treatment with warfarin and NOAC. Results The median LOS for NOACs-treated patients was 12.5 days and that for warfarin treated patients was 19.0 days while the corresponding mean medical costs were USD 7151 ± 6228 [JPY 736,546 ± 641,437] and USD 8950 ± 5891 [JPY 921,830 ± 606,765]. The drug cost for NOACs-treated patients was higher but costs for laboratory-test and hospitalization were lower than those for warfarin-treated patients. Conclusions For NOAC-treated patients, LOS was shorter, and medical cost during hospitalization tended to be lower than those for warfarin-treated patients, whereas NOACs prices were higher than warfarin price.

[Is necessary to perform a transthoracic echocardiogram in all the patients with cryptogenic stroke during hospitalization?]. / Es necesaria la realizacion de un ecocardiograma transtoracico a todos los pacientes con ictus isquemico indeterminado durante el ingreso?

INTRODUCTION: From 15 to 30% of all ischemic strokes are cardioembolic. Transthoracic echocardiography plays a key role in the evaluation, diagnosis and management of the embolic source. The absence of official recommendations for the use of echocardiography in patients with ischemic stroke leads to a universal application showing low diagnostic efficiency. AIM: To analyze the diagnostic accuracy of echocardiograpm in patients with ischemic stroke in two situations: with universal indication and after the application of risk clinical criteria. PATIENTS AND METHODS: Analysis of the echocardiograms performed on patients with acute ischemic stroke from the stroke unit during the years 2009-2011. We study the diagnostic and etiological contribution to the etiological study. Apply a selection criteria: 'high risk patient with need of test performance during admission' (age < 60 years, abnormal baseline electrocardiogram, cardiomegaly on chest radiograph or baseline history of heart disease, suspected endocarditis and/or active neoplasia) and analyzed their validity. RESULTS: From 930 inpatients, 201 (21.6%), underwent echocardiogram. Cardioembolic source was detected in 9.95%. After application of selection criteria, only 97 patients (10.4%) should have undergone it. The proposed criteria have a sensitivity 95%, specificity 56.9%, positive predictive value 19.6% and negative predictive value of 99%. CONCLUSIONS: The application of our criteria in undetermined stroke patients help us to identify with high efficiency cardioembolic sources postponing the test to an ambulatory scenario in the rest of the patients.

TITLE: Es necesaria la realizacion de un ecocardiograma transtoracico a todos los pacientes con ictus isquemico indeterminado durante el ingreso?Introduccion. El 15-30% de los ictus isquemicos son de origen cardioembolico. El ecocardiograma transtoracico desempena un papel fundamental en la evaluacion, diagnostico y manejo de la fuente embolica. La ausencia de recomendaciones oficiales para el empleo del ecocardiograma en pacientes con ictus isquemico lleva a una solicitud universal de la prueba, presentando una baja rentabilidad diagnostica. Objetivo. Analizar la rentabilidad diagnostica del ecocardiograma transtoracico en pacientes con ictus isquemico indeterminado tras la aplicacion de criterios clinicos predefinidos de riesgo. Pacientes y metodos. Se analizan los ecocardiogramas realizados a pacientes con ictus isquemico agudo solicitados durante 2009-2011 desde el servicio de neurologia. Se estudia la rentabilidad diagnostica y su aportacion al estudio etiologico. Se aplican unos 'criterios de seleccion de paciente de alto riego con necesidad de realizacion de la prueba durante el ingreso' (edad < 60 anos, alteraciones en el ecocardiograma basal, cardiomegalia en la radiografia de torax basal, antecedentes de cardiopatia, sospecha clinica de endocarditis o neoplasia activa) y se analiza su validez. Resultados. De 930 pacientes, se realizo ecocardiograma a 201 (21,6%) y se detecto una fuente cardioembolica en el 9,95%. Tras la aplicacion de criterios de seleccion, el numero de ecocardiogramas paso a 97 (10,4%). Los criterios propuestos presentan: sensibilidad, 95%; especificidad, 56,9%; valor predictivo positivo, 19,6%, y valor predictivo negativo, 99%. Conclusiones. La aplicacion de nuestros criterios a pacientes con ictus indeterminado identifica con alta eficiencia la fuente cardioembolica, lo que permite la realizacion del ecocardiograma transtoracico ambulatorio en el resto de los pacientes.

Cost-effectiveness analysis of the neuroprotective agent edaravone for noncardioembolic cerebral infarction.

BACKGROUND: The free radical scavenger edaravone has been reported useful for improvement in activities of daily living and for prevention of recurrent stroke in the edaravone versus sodium ozagrel in acute noncardioembolic ischemic stroke (EDO) trial. The aim of this report was to evaluate the cost-effectiveness of edaravone compared to the intravenous antiplatelet drug ozagrel sodium (ozagrel) for noncardioembolic stroke (non-CES) based on the EDO trial data. METHODS: A cost-effectiveness analysis was performed using the Markov model, which also incorporated the long-term course after the acute stage of non-CES. From the perspective of a health care payer, direct medical costs and nursing care costs were taken into account in the cost analysis. The quality-adjusted life year (QALY) served as an indicator of effectiveness. Simulation at 5 and 10 years after the onset of non-CES was carried out. The study involved 68-year-old patients with non-CES, selected against the EDO trial subject selection criteria. A 14-day treatment with edaravone 60 mg/day or ozagrel 160 mg/day was assumed as acute treatment for non-CES. RESULTS: The use of edaravone was associated with a reduction in total costs (0.51 million yen [$6,374] at 5 years and 0.64 million yen [$8,039]) at 10 years after the onset of non-CES) and improvement in QALYs (0.23 at 5 years and 0.38 at 10 years). Compared to ozagrel therapy, edaravone therapy was a cost-saving strategy for treating non-CES. CONCLUSIONS: Compared to ozagrel therapy, edaravone therapy for non-CES is not only useful from a clinical viewpoint, but also valuable from a socioeconomic perspective.

[Social impact of stroke due to atrial fibrillation]. / Impacto social del ictus producido por fibrilación auricular.

Atrial fibrillation (AF) is the most frequent heart arrhythmia and causes a substantial proportion of ischemic strokes. AF has a marked impact on stroke severity, as well as on morbidity and mortality in these patients. The importance of AF as an etiologic factor of stroke increases in the elderly and in the last few years its detection has increased. The presence of AF leads to more severe initial neurological involvement, longer hospitalization, greater disability and a lower probability of discharge to home. In addition, AF is an independent risk factor for mortality, especially in women and the elderly. All these factors lead to a higher social and economic impact among stroke patients with AF.

Cost-effectiveness of dabigatran compared with warfarin for stroke prevention in patients with atrial fibrillation and prior stroke or transient ischemic attack.

BACKGROUND AND PURPOSE: The cost-effectiveness of dabigatran for stroke prevention in patients with atrial fibrillation and prior stroke or transient ischemic attack has not been directly assessed. METHODS: A Markov decision model was constructed using data from the Randomized Evaluation of Long-Term Therapy (RE-LY) trial, other trials of warfarin therapy for atrial fibrillation, and the published cost of dabigatran. We compared the cost and quality-adjusted life expectancy associated with 150 mg dabigatran twice daily versus warfarin therapy targeted to an international normalized ratio of 2 to 3. The target population was a cohort of patients aged ≥70 years with nonvalvular atrial fibrillation, prior stroke or transient ischemic attack, and no contraindication to anticoagulation. RESULTS: In the base case, dabigatran was associated with 4.27 quality-adjusted life-years compared with 3.91 quality-adjusted life-years with warfarin. Dabigatran provided 0.36 additional quality-adjusted life-years at a cost of $9000, yielding an incremental cost-effectiveness ratio of $25,000. In sensitivity analyses, the cost-effectiveness of dabigatran was inversely related to the quality of international normalized ratio control achieved with warfarin therapy. In Monte Carlo analysis, dabigatran was cost-effective in 57% of simulations using a threshold of $50,000 per quality-adjusted life-year and 78% of simulations using a threshold of $100,000 per quality-adjusted life-year. CONCLUSIONS: Dabigatran appears to be cost-effective relative to warfarin for stroke prevention in patients with atrial fibrillation and prior stroke or transient ischemic attack. Our analysis is limited by its reliance on data from a substudy of a single randomized trial, and our results may not apply in settings with uncommonly good international normalized ratio control using warfarin.

Cost-effectiveness of genotype-guided warfarin therapy for anticoagulation in elderly patients with atrial fibrillation.

BACKGROUND: In patients with atrial fibrillation (AF), anticoagulation with warfarin decreases the risk of embolic stroke by >50%. Identification of genetic polymorphisms in enzymes involved in the metabolism of warfarin can partially predict the maintenance dose and thus potentially decrease the incidence of bleeding episodes secondary to warfarin overdose. OBJECTIVES: The objectives of this study were to evaluate the potential clinical and economic outcomes of genotype-guided warfarin therapy in elderly patients newly diagnosed with AF and to identify a threshold in bleeding risk at which such therapy may be cost-effective. METHODS: A decision tree was designed to represent the medical decision (pharmacogenetic testing or not) and the main clinical outcomes (embolic stroke, bleeding). Event rates of embolic stroke and bleeding complications were based on data from previously published clinical trials and an observational study, respectively; costs were from a third-party payer perspective; and utilities were from the patient perspective. It was assumed that use of pharma-cogenetic testing would not lead the clinician to make any potentially harmful modifications to the regimen. RESULTS: This analysis found that any reduction in major bleeding as a result of pharmacogenetic testing would lead to improved utility. The higher costs of pharmacogenetic testing compared with no testing would be immediately offset by any reduction in major bleeding. CONCLUSIONS: In this decision analysis, genotype-guided warfarin therapy for anticoagulation in elderly patients with AF was potentially cost-effective, and its benefits were closely related to efficacy in preventing bleeding events. Clinical trials testing the efficacy of genotype-guided warfarin therapy are warranted.

Evaluation of costs and outcome in cardioembolic stroke or TIA.

The costs of acute stroke care, length of hospital stay (LOS), and outcome in patients with cardioembolic stroke or cardioembolic transient ischemic attacks (TIA) were investigated with the aim of estimating the clinical and health-economic impacts of cerebral cardioembolism. The study population consisted of 511 consecutive patients with the diagnosis of ischemic stroke (n = 379) or TIA (n = 132) treated at the Department of Neurology, Philipps University, Marburg. Cerebral cardioembolism was defined according to the criteria of the Cerebral Embolism Task Force. Clinical status was assessed by means of Barthel index (BI) and modified Rankin Scale. Costs were calculated using a bottom-up approach. All costs (in Euros) were inflated to the 2008 level. Compared to non-cardioembolic stroke (n = 278) patients, patients who had suffered cardioembolic stroke (n = 101) had more severe clinical deficits on admission (BI 46.3 +/- 27.0 vs. 59.3 +/- 34.1; P < 0.01), worse recovery (BI on discharge 59.2 +/- 28.9 vs. 73.1 +/- 33.4; P < 0.01), and increased LOS (12.6 +/- 5.7 vs. 10.0 +/- 7.8 days; P < 0.01). The latter also required a relatively higher daily resource utilization due to increased expenses for personnel and diagnostics. Mean costs of acute care for patients with cardioembolic stroke [euro 4890 per patient (95% confidence interval 4460-5200)] were significantly higher than those for patients with non-cardioembolic stroke [euro 3550 (95% confidence interval 3250-3850); P < 0.01]. The clinical and health-economic impact of cardiogenic cerebral embolism on stroke care is considerable. Patients with cardioembolic stroke/TIA are more severely impaired, and they require longer hospital treatment and increased resource utilization. Costs of acute care of cardioembolic stroke/TIA patients may exceed those of non-cardioembolic stroke/TIA by up to 40%.

Should routine echocardiography be performed in all patients with stroke?

BACKGROUND: Cardiogenic embolism accounts for 15% to 30% of ischemic strokes. Echocardiography is frequently being used as a screening test for sources of cardiac embolism in patients with stroke. However, the value of routine use of echocardiography for this task remains controversial. We evaluated the diagnostic yield of echocardiography in unselected patients with acute ischemic stroke. METHODS: Consecutive patients with ischemic stroke or a transient ischemic attack were included in the study. Transthoracic echocardiography was performed in all patients, complemented by transesophageal echocardiography in selected patients. RESULTS: In all, 807 echocardiographic examinations (743 transthoracic and 64 transesophageal) were performed in 775 consecutive patients. A potential cardiac source of embolism (CSE) was found in 144 (18%) of the patients. The most frequent potential causes of cardiac embolism included atrial fibrillation (7%) and patent foramen ovale (6%). Results were more likely to have impact on therapeutic decisions in younger patients. Numbers needed to test for detection of CSE increased 10-fold from 6 in patients younger than 50 years to 62 in patients aged 70 years and older. CONCLUSION: Echocardiography may provide important information on the cause of ischemic stroke. However, echocardiographic screening for a CSE is not warranted in all patients. In patients with younger than 50 years with stroke, echocardiography has a higher diagnostic yield and should routinely be performed. In older patients routine echocardiography results in a high rate of unspecific findings, and should be applied selectively, targeted at specific clinical questions.