Cost-Effectiveness of Increased Use of Dual Antiplatelet Therapy After High-Risk Transient Ischemic Attack or Minor Stroke.

BACKGROUND: Rates of dual antiplatelet therapy (DAPT) after high-risk transient ischemic attack or minor ischemic stroke (TIAMIS) are suboptimal. We performed a cost-effectiveness analysis to characterize the parameters of a quality improvement (QI) intervention designed to increase DAPT use after TIAMIS. METHODS AND RESULTS: We constructed a decision tree model that compared current national rates of DAPT use after TIAMIS with rates after implementing a theoretical QI intervention designed to increase appropriate DAPT use. The base case assumed that a QI intervention increased the rate of DAPT use to 65% from 45%. Costs (payer and societal) and outcomes (stroke, myocardial infarction, major bleed, or death) were modeled using a lifetime horizon. An incremental cost-effectiveness ratio <$100 000 per quality-adjusted life year was considered cost-effective. Deterministic and probabilistic sensitivity analyses were performed. From the payer perspective, a QI intervention was associated with $9657 in lifetime cost savings and 0.18 more quality-adjusted life years compared with current national treatment rates. A QI intervention was cost-effective in 73% of probabilistic sensitivity analysis iterations. Results were similar from the societal perspective. The maximum acceptable, initial, 1-time payer cost of a QI intervention was $28 032 per patient. A QI intervention that increased DAPT use to at least 51% was cost-effective in the base case. CONCLUSIONS: Increasing DAPT use after TIAMIS with a QI intervention is cost-effective over a wide range of costs and proportion of patients with TIAMIS treated with DAPT after implementation of a QI intervention. Our results support the development of future interventions focused on increasing DAPT use after TIAMIS.

Allopurinol and cardiovascular outcomes in patients with ischaemic heart disease: the ALL-HEART RCT and economic evaluation.

Background: Allopurinol is a xanthine oxidase inhibitor that lowers serum uric acid and is used to prevent acute gout flares in patients with gout. Observational and small interventional studies have suggested beneficial cardiovascular effects of allopurinol. Objective: To determine whether allopurinol improves major cardiovascular outcomes in patients with ischaemic heart disease. Design: Prospective, randomised, open-label, blinded endpoint multicentre clinical trial. Setting: Four hundred and twenty-four UK primary care practices. Participants: Aged 60 years and over with ischaemic heart disease but no gout. Interventions: Participants were randomised (1 : 1) using a central web-based randomisation system to receive allopurinol up to 600 mg daily that was added to usual care or to continue usual care. Main outcome measures: The primary outcome was the composite of non-fatal myocardial infarction, non-fatal stroke or cardiovascular death. Secondary outcomes were non-fatal myocardial infarction, non-fatal stroke, cardiovascular death, all-cause mortality, hospitalisation for heart failure, hospitalisation for acute coronary syndrome, coronary revascularisation, hospitalisation for acute coronary syndrome or coronary revascularisation, all cardiovascular hospitalisations, quality of life and cost-effectiveness. The hazard ratio (allopurinol vs. usual care) in a Cox proportional hazards model was assessed for superiority in a modified intention-to-treat analysis. Results: From 7 February 2014 to 2 October 2017, 5937 participants were enrolled and randomised to the allopurinol arm (n = 2979) or the usual care arm (n = 2958). A total of 5721 randomised participants (2853 allopurinol; 2868 usual care) were included in the modified intention-to-treat analysis population (mean age 72.0 years; 75.5% male). There was no difference between the allopurinol and usual care arms in the primary endpoint, 314 (11.0%) participants in the allopurinol arm (2.47 events per 100 patient-years) and 325 (11.3%) in the usual care arm (2.37 events per 100 patient-years), hazard ratio 1.04 (95% confidence interval 0.89 to 1.21); p = 0.65. Two hundred and eighty-eight (10.1%) participants in the allopurinol arm and 303 (10.6%) participants in the usual care arm died, hazard ratio 1.02 (95% confidence interval 0.87 to 1.20); p = 0.77. The pre-specified health economic analysis plan was to perform a 'within trial' cost-utility analysis if there was no statistically significant difference in the primary endpoint, so NHS costs and quality-adjusted life-years were estimated over a 5-year period. The difference in costs between treatment arms was +£115 higher for allopurinol (95% confidence interval £17 to £210) with no difference in quality-adjusted life-years (95% confidence interval -0.061 to +0.060). We conclude that there is no evidence that allopurinol used in line with the study protocol is cost-effective. Limitations: The results may not be generalisable to younger populations, other ethnic groups or patients with more acute ischaemic heart disease. One thousand six hundred and thirty-seven participants (57.4%) in the allopurinol arm withdrew from randomised treatment, but an on-treatment analysis gave similar results to the main analysis. Conclusions: The ALL-HEART study showed that treatment with allopurinol 600 mg daily did not improve cardiovascular outcomes compared to usual care in patients with ischaemic heart disease. We conclude that allopurinol should not be recommended for the secondary prevention of cardiovascular events in patients with ischaemic heart disease but no gout. Future work: The effects of allopurinol on cardiovascular outcomes in patients with ischaemic heart disease and co-existing hyperuricaemia or clinical gout could be explored in future studies. Trial registration: This trial is registered as EU Clinical Trials Register (EudraCT 2013-003559-39) and ISRCTN (ISRCTN 32017426). Funding: This award was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme (NIHR award ref: 11/36/41) and is published in full in Health Technology Assessment; Vol. 28, No. 18. See the NIHR Funding and Awards website for further award information.

The purpose of the ALL-HEART study was to determine whether giving allopurinol to people with ischaemic heart disease (also commonly known as coronary heart disease) would reduce their risk of having a heart attack, stroke or of dying from cardiovascular disease. Allopurinol is a medication usually given to patients with gout to prevent acute gout flares. It is not currently used to treat ischaemic heart disease. We randomly allocated people aged over 60 years with ischaemic heart disease to take up to 600 mg of allopurinol daily (in addition to their usual care) or to continue with their usual care. We then monitored participants for several years and recorded any major health events such as heart attacks, strokes and deaths. We obtained most of the follow-up data from centrally held electronic hospital admissions and death records, making the study easier for participants and more cost-efficient. We asked participants in both groups to complete questionnaires to assess their quality of life during the study. We also collected data to determine whether there was any economic benefit to the NHS of using allopurinol in patients with ischaemic heart disease. There was no difference in the risk of heart attacks, strokes or death from cardiovascular disease between the participants given allopurinol and those in the group continuing their usual care. We also found no difference in the risks of other cardiovascular events, deaths from any cause or quality-of-life measurements between the allopurinol and usual care groups. The results of the ALL-HEART study suggest that we should not recommend that allopurinol be given to people with ischaemic heart disease to prevent further cardiovascular events or deaths.

Stroke genetics and how it Informs novel drug discovery.

INTRODUCTION: Stroke is one of the main causes of death and disability worldwide. Nevertheless, despite the global burden of this disease, our understanding is limited and there is still a lack of highly efficient etiopathology-based treatment. It is partly due to the complexity and heterogenicity of the disease. It is estimated that around one-third of ischemic stroke is heritable, emphasizing the importance of genetic factors identification and targeting for therapeutic purposes. AREAS COVERED: In this review, the authors provide an overview of the current knowledge of stroke genetics and its value in diagnostics, personalized treatment, and prognostication. EXPERT OPINION: As the scale of genetic testing increases and the cost decreases, integration of genetic data into clinical practice is inevitable, enabling assessing individual risk, providing personalized prognostic models and identifying new therapeutic targets and biomarkers. Although expanding stroke genetics data provides different diagnostics and treatment perspectives, there are some limitations and challenges to face. One of them is the threat of health disparities as non-European populations are underrepresented in genetic datasets. Finally, a deeper understanding of underlying mechanisms of potential targets is still lacking, delaying the application of novel therapies into routine clinical practice.

Efficacy, safety, and cost-effectiveness analysis of Cerebrolysin in acute ischemic stroke: A rapid health technology assessment.

This study conducts a rapid health technology assessment to systematically evaluate the effectiveness, safety, and cost-effectiveness of Cerebrolysin as an adjunctive therapy for acute ischemic stroke to provide evidence-based medicine for clinical decisions of Cerebrolysin. All systematic reviews/meta-analyses, pharmacoeconomic studies, and health technology assessment reports of Cerebrolysin for the treatment of acute ischemic stroke before August 17, 2023, were retrieved from PubMed, Embase, Cochrane Library, China National Knowledge Infrastructure, Wanfang, Weipu, Sinomed database and the official website of health technology assessment. According to the inclusion and exclusion criteria, 2 researchers independently carried out screening, data extraction, and quality evaluation and descriptively analyzed the results of the included studies. A total of 14 pieces of literature were incorporated, comprising 8 systematic reviews/meta-analyses and 6 pharmacoeconomic studies. In terms of effectiveness, compared to control groups, the use of Cerebrolysin as a treatment for acute ischemic stroke demonstrates certain advantages, including enhancement in total efficacy rate, neurological function, upper limb motor dysfunction, and facilitation of the recovery of activities of daily living. Especially in patients with moderate to severe acute ischemic stroke, Cerebrolysin has demonstrated the ability to enhance neurological function recovery and ameliorate disabilities. Regarding safety, adverse reactions were mild or comparable to those in the control group. The primary findings of economic studies reveal that advocating for the use of Cerebrolysin offers certain cost-effectiveness advantages. Cerebrolysin contributes to improved clinical efficacy and evaluation indexes while demonstrating favorable safety and economic benefits.

Cost-effectiveness of edaravone dexborneol versus dl-3-n-butylphthalide for the treatment of acute ischemic stroke: a Chinese health care perspective.

BACKGROUND: Edaravone dexborneol and dl-3-n-butylphthalide are two innovative brain cytoprotective drugs from China that have been approved and widely prescribed for acute ischemic stroke, and the cost of the two drugs are partially paid by the Chinese medical insurance system. This study aimed to investigate and compare the cost-effectiveness of edaravone dexborneol versus dl-3-n-butylphthalide for acute ischemic stroke from the Chinese healthcare system's perspective. METHODS: A model combining a short-term decision tree model with 90 days and a long-term Markov model with a life-time horizon (40 years) was developed to simulate the cost-effectiveness of edaravone dexborneol versus dl-3-n-butylphthalide for acute ischemic stroke over a lifetime horizon. Since the absence of a head-to-head clinical comparison of two therapies, an unanchored matching-adjusted indirect comparison (MAIC) was conducted by adjusting the patient characteristics using individual patient data from pivotal phase III trial of edaravone dexborneol and published aggregated data of dl-3-n-butylphthalide. Health outcomes were measured in quality-adjusted life years (QALYs). Utilities and costs (Chinese Yuan, CNY) were derived from publications and open-access database. One-way and probabilistic sensitivity analyses were performed to evaluate the robustness of results. RESULTS: Compared with patients in dl-3-n-butylphthalide arm, edaravone dexborneol arm was found to be cost-effective in 90 days and highly cost-effective as the study horizons extended. With a similar direct medical cost, patients in edaravone dexborneol arm slightly gained an additional 0.1615 QALYs in life-time. In the long term (40 years), patients in edaravone dexborneol arm and dl-3-n-butylphthalide arm yielded 8.0351 and 7.8736 QALYs with the overall direct medical cost of CNY 29,185.23 and CNY 29,940.28, respectively. The one-way sensitivity analysis suggested that the incremental cost-effectiveness ratio was most sensitive to the price of edaravone dexborneol and dl-3-n-butylphthalide. CONCLUSION: Edaravone dexborneol is a cost-effective alternative compared with dl-3-n-butylphthalide for acute ischemic stroke patients in current medical setting of China.

Cost-effectiveness of tirofiban for acute ischemic stroke without large or medium-sized vessel occlusion: A Markov modelling analysis from the Chinese and United States perspectives.

BACKGROUND: The RESCUE BT2 trial recently showcased the efficacy of tirofiban in treating acute ischemic stroke (AIS) without large or medium-sized vessel occlusion. To further assess the value of tirofiban from the perspectives of Chinese and US healthcare system, a study was conducted to evaluate its cost-effectiveness. METHODS: A hybrid model, integrating a short-term decision tree with a long-term Markov model, was developed to assess cost-effectiveness between tirofiban and aspirin for stroke patients without large or medium-sized vessel occlusion. Efficacy data for tirofiban was sourced from the RESCUE BT2 trial, while cost information was derived from published papers. Outcomes measured included respective cost, effectiveness, and incremental cost-effectiveness ratio (ICER). We conducted a one-way sensitivity analysis to assess the robustness of the results. Additionally, we performed probabilistic sensitivity analysis (PSA) through 10,000 Monte Carlo simulations to evaluate the uncertainties associated with the results. RESULTS: The study revealed that tirofiban treatment in AIS patients without large or medium-sized vessel occlusion led to a considerable reduction of 2141 Chinese Yuan (CNY) in total cost, along with a lifetime gain of 0.14 quality-adjusted life years (QALYs). In the US settings, tirofiban also exhibited a lower cost ($197,055 versus $201,984) and higher effectiveness (4.15 QALYs versus 4.06 QALYs) compared to aspirin. One-way sensitivity analysis revealed that post-stroke care costs and stroke utility had the greatest impact on ICER fluctuation in both Chinese and US settings. However, these variations did not exceed the willingness-to-pay threshold. PSA demonstrated tirofiban's superior acceptability over aspirin in over 95% of potential scenarios. CONCLUSION: Tirofiban treatment for AIS without large or medium-sized vessel occlusion appeared dominant compared to aspirin in both China and the US.

Empiric treatment with aspirin and ticagrelor is the most cost-effective strategy in patients with minor stroke or transient ischemic attack.

BACKGROUND: Patients with minor ischemic stroke or transient ischemic attacks (TIAs) are often treated with dual antiplatelet therapy regimens as part of secondary stroke prevention. Clopidogrel, an antiplatelet used in these regimens, is metabolized into its active form by the CYP2C19 enzyme. Patients with loss of function (LOF) mutations in CYP2C19 are at risk for poorer secondary outcomes when prescribed clopidogrel. AIMS: We aimed to determine the cost-effectiveness of three different treatment antiplatelet regimens in ischemic stroke populations with minor strokes or TIAs and how these treatment regimens are influenced by the LOF prevalence in the population. METHODS: Markov models were developed to look at the cost-effectiveness of empiric treatment with aspirin and clopidogrel versus empiric treatment with aspirin and ticagrelor, versus genotype-guided therapy for either 21 or 30 days. Effect ratios were obtained from the literature, and incidence rates and costs were obtained from the national data published by the Singapore Ministry of Health. The primary endpoints were the incremental cost-effectiveness ratios (ICERs). RESULTS: Empiric treatment with aspirin and ticagrelor was the most cost-effective treatment. Genotype-guided therapy was more cost-effective than empiric aspirin and clopidogrel if the LOF was above 48%. Empiric ticagrelor and aspirin was cost saving when compared to genotype-guided therapy. Results in models of dual antiplatelet therapy for 30 days were similar. CONCLUSION: This study suggests that in patients with minor stroke and TIA planned for dual antiplatelet regimens, empiric ticagrelor and aspirin is the most cost-effective treatment regimen. If ticagrelor is not available, genotype-guided therapy is the most cost-effective treatment regimen if the LOF prevalence in the population is more than 48%.

Signal detection of adverse events associated with gabapentinoid use for chronic pain.

INTRODUCTION: Gabapentinoids (GABA) prescribing as a potential and conceivably safer substitute for opioids has substantially increased. Understanding all potential adverse drug events (ADEs) associated with GABA will guide clinical decision-making for pain management. METHODS: A 20% sample of Medicare enrollees with new chronic pain diagnoses in 2017-2018 was selected. GABA users were those with >=30 consecutive days prescription in a year without opioid prescription. Opioid users were similarly defined. The control group used neither of these drugs. Propensity score match across three groups based on demographics and comorbidity was performed. We used proportional reporting ratio (PRR), Gamma Poisson Shrinker, and tree-based scan statistic (TBSS) to detect ADEs within 3, 6, and 12 months of follow-up. RESULTS: Immunity disorder was detected within 3 months of follow-up by PRR compared to opioid use (PRR:2.33), and by all three methods compared to controls. Complications of transplanted organs/tissues and schizophrenia spectrum/other psychotic disorders were consistently detected by PRR and TBSS within 3 months. Skin disorders were detected by TBSS; and stroke was detected by PRR within 3 months compared to opioid use (PRR:4.74). Some malignancies were detected by PRR within 12 months. Other signals detected in GABA users were neuropathy and nerve disorders. CONCLUSIONS: Our study identified expected and unexpected ADE signals in GABA users. Neurological signals likely related to indications for GABA use. Signals for immunity, mental/behavior, and skin disorders were found in the FDA adverse event reporting system database. Unexpected signals of stroke and cancer require further confirmatory analyses to verify.

Cost-effectiveness analysis of CYP2C19 genotype-guided antiplatelet therapy for patients with acute minor ischemic stroke and high-risk transient ischemic attack in China.

AIMS: The study aimed to estimate the cost-effectiveness of CYP2C19 genotype-guided antiplatelet therapy using cilostazol and ticagrelor as an alternative to clopidogrel, compared to conventional antiplatelet therapy with clopidogrel and aspirin. METHODS: A 90-day decision tree and 30-year Markov model were employed to assess the costs and quality-adjusted life years (QALYs) of personalized antiplatelet therapy for patients with minor ischemic stroke and high-risk transient ischemic attack, compared to conventional antiplatelet therapy in the Chinese healthcare system. The primary outcome was the incremental cost-effectiveness ratio (ICER). The data sources included clinical trials, published literature, official documents and local prices. One-way sensitivity analysis and probabilistic sensitivity analysis were performed to confirm the robustness of the findings. RESULTS: The base-case analysis indicated that the CYP2C19 genotype-guided antiplatelet strategy was cost-effective, and cilostazol group and ticagrelor group yielded an ICER of 3327.40 US dollars (USD)/QALY and 3426.92 USD/QALY, respectively, which were less than threshold. The one-way sensitivity analysis showed the results were robust, where the most sensitive parameter was the disability distribution in the modified Rankin scale 3-5. The probabilistic analysis showed that the CYP2C19 genotype-guided antiplatelet therapy with either cilostazol or ticagrelor was 100% cost-effective under the willingness-to-pay threshold. CONCLUSIONS: CYP2C19 genotype-guided antiplatelet therapy using cilostazol and ticagrelor as an alternative to clopidogrel appeared to be more cost-effective than conventional antiplatelet therapy for acute minor ischemic stroke and high-risk transient ischemic attack patients over 30 years in China.

Endovascular Thrombectomy with or without Bridging Thrombolysis in Acute Ischemic Stroke: A Cost-Effectiveness Analysis.

BACKGROUND: There is unclear added benefit of intravenous thrombolysis (IVT) with endovascular thrombectomy (EVT). We performed a cost-effectiveness analysis to assess the cost-effectiveness of comparing EVT with IVT versus EVT alone. METHODS: We used a decision tree to examine the short-term costs and outcomes at 90 days after the occurrence of index stroke to compare the cost-effectiveness of EVT alone with EVT plus IVT for patients with stroke. Subsequently, we developed a Markov state transition model to assess the costs and outcomes over 1-year, 5-year, and 20-year time horizons. We estimated total and incremental cost, quality-adjusted life years (QALYs), and incremental cost-effectiveness ratio. RESULTS: The average costs per patient were estimated to be $47,304, $49,510, $59,770, and $76,561 for EVT-only strategy and $55,482, $57,751, $68,314, and $85,611 for EVT with IVT over 90 days, 1 year, 5 years, and 20 years, respectively. The cost saving of EVT-only strategy was driven by the avoided medication costs of IVT (ranging from $8,178 to $9,050). The additional IVT led to a slight decrease in QALY estimate during the 90-day time horizon (loss of 0.002 QALY), but a small gain over 1-year and 5-year time horizons (0.011 and 0.0636 QALY). At a willingness-to-pay threshold of $50,000 per QALY gained, the probabilities of EVT only being cost-effective were 100%, 100%, and 99.3% over 90-day, 1-year, and 5-year time horizons. CONCLUSION: Our cost-effectiveness model suggested that EVT only may be cost-effective for patients with acute ischemic stroke secondary to large vessel occlusion.

Performance of modeling and balancing approach methods when using weights to estimate treatment effects in observational time-to-event settings.

In observational studies weighting techniques are often used to overcome bias due to confounding. Modeling approaches, such as inverse propensity score weighting, are popular, but often rely on the correct specification of a parametric model wherein neither balance nor stability are targeted. More recently, balancing approach methods that directly target covariate imbalances have been proposed, and these allow the researcher to explicitly set the desired balance constraints. In this study, we evaluate the finite sample properties of different modeling and balancing approach methods, when estimating the marginal hazard ratio, through Monte Carlo simulations. The use of the different methods is also illustrated by analyzing data from the Swedish stroke register to estimate the effect of prescribing oral anticoagulants on time to recurrent stroke or death in stroke patients with atrial fibrillation. In simulated scenarios with good overlap and low or no model misspecification the balancing approach methods performed similarly to the modeling approach methods. In scenarios with bad overlap and model misspecification, the modeling approach method incorporating variable selection performed better than the other methods. The results indicate that it is valuable to use methods that target covariate balance when estimating marginal hazard ratios, but this does not in itself guarantee good performance in situations with, e.g., poor overlap, high censoring, or misspecified models/balance constraints.

[Therapies for the Improvement of Stroke Recovery - Assessment of Clinical Trial Results]. / Therapien zur Verbesserung der Schlaganfall-Regeneration ­ Ergebnisse klinischer Studien im wissenschaftlichen Kontext.

Recovery processes after stroke include restoration or compensation of function initially lost or newly acquired after injury. Therapeutic interventions can either directly improve these processes and/or inhibit processes that impede regeneration. Numerous experimental studies suggested a great opportunity for such treatments, but the results from recent large clinical trials with neuromodulators such as dopamine and fluoxetine have been rather disappointing. The reasons for this are manifold and involve the extrapolation of results from animal models to humans. Given the differences between animals and humans in genetic and epigenetic background, brain size and anatomy, cerebral vascular anatomy, immune system, as well as clinical function, and behavior, direct extrapolation is unlikely to work. Backward blockades include the incompatible adaption of clinical trial objectives and outcomes in clinical trials with regard to previous preclinical findings. For example, the clinical recovery trial design widely varies and has been characterized by the selection of different clinical endpoints, the inclusion a wide spectrum of stroke subtypes and clinical syndromes, and different time windows for treatment initiation after onset of infarction. This review will discuss these aspects based on the results of the recent stroke recovery trials with the aim to contributing to the development of a therapy that improves the functional outcome of a chronic stroke patient.

Stroke pathway performance assessment: a retrospective observational study.

BACKGROUND AND AIM: Performance assessment of the Stroke Pathway is a key element in healthcare quality. The aim of this study has been to carry out a retrospective assessment of the Stroke Pathway in a first level Stroke Unit in Italy, analyzing the temporal trend of the Stroke Pathway performance and the impact of the COVID-19 pandemic. METHODS: A retrospective observational study was carried out analyzing data from 1/01/2010 to 31/12/2020. The following parameters were considered: volume and characteristics of patients with ischemic stroke undergoing intravenous thrombolysis, baseline modified Rankin Scale (mRS) and National Institutes of Health Stroke Scale (NIHSS) scores, Onset-to-Door (OTD), Door-To-Imaging (DTI) and Door-To-Needle (DTN) Times, mRS score 3 months after the ischemic event onset (3 m-mRS) and NIHSS score 24 h after the ischemic event onset (24 h-NIHSS). The study also compared the pre-COVID-19 pandemic period (March-December 2019) with the one immediately following it (March-December 2020). RESULTS: 418 patients were included. Over time, treatment was extended to older patients (mean age from 66.3 to 75.51 years; p = 0.006) and with a higher level of baseline disability (baseline mRS score from 0.22 to 1.22; p = 0.000). A statistically significant reduction over the years was found for DTN, going from 90 min to 61 min (p = 0.000) with also an increase in the number of thrombolysis performed within the "golden hour" - more than 50% in 2019 and more of 60% in 2020. Comparing pre- and during COVID-19 pandemic periods, the number of patients remained almost unchanged, but with a significantly higher baseline disability (mRS = 1.18 vs. 0.72, p = 0.048). The pre-hospital process indicator OTD increased from 88.13 to 118.48 min, although without a statistically significant difference (p = 0.197). Despite the difficulties for hospitals due to pandemic, the hospital process indicators DTI and DTN remained substantially unchanged, as well as the clinical outcome indicators 3 m-mRS, NHISS and 24 h-NHISS. CONCLUSIONS: The results of the retrospective assessment of the Stroke Pathway highlighted its positive impact both on hospital processes and patients' outcomes, even during the COVID-19 pandemic, so that the current performance is aligning itself with international goals. Moreover, the analysis showed the need of improvement actions for both hospital and pre-hospital phases. The Stroke Pathway should be improved with the thrombolysis starting in the diagnostic imaging department in order to further reduce the DTN score. Moreover, health education initiatives involving all the stakeholders should be promoted, also by using social media, to increase population awareness on timely recognition of stroke signs and symptoms and emergence medical services usage.

Atrial fibrillation and mortality after ischemic stroke: An observational study using an insurance claim database.

OBJECTIVES: In this study, we aimed to examine the association between atrial fibrillation and mortality after ischemic stroke and evaluate the use of anticoagulation therapy for atrial fibrillation before stroke onset in patients who experienced stroke. METHODS: In this retrospective observational study, we used a combined database of medical and long-term care insurance claims data from one prefecture in Japan. The data of 25,352 patients aged ≥ 65 years who were hospitalized in acute care hospitals with a diagnosis of ischemic stroke between April 2012 and March 2015 were extracted. Cox proportional hazard modeling, with adjustment for age, sex, comorbidities, and long-term care dependency level (based on the activities of daily living), was performed to evaluate the relationship between mortality and atrial fibrillation. RESULTS: The prevalence of atrial fibrillation was 21.8% in the study population. A significant association was noted between mortality and atrial fibrillation (adjusted hazard ratio: 1.28, 95% confidence interval: 1.16-1.41, p < 0.001). Anticoagulant drugs were used in 32.2% of the patients with atrial fibrillation. CONCLUSIONS: These results indicate that atrial fibrillation is associated with mortality after stroke; however, the use of anticoagulation therapy for atrial fibrillation is unsatisfactory. Efforts to improve the use of atrial fibrillation therapy are required in Japan.

Rates and reasons for hospital readmission after acute ischemic stroke in a US population-based cohort.

Hospital readmissions following stroke are costly and lead to worsened patient outcomes. We examined readmissions rates, diagnoses at readmission, and risk factors associated with readmission following acute ischemic stroke (AIS) in a large United States (US) administrative database. Using the 2019 Nationwide Readmissions Database, we identified adults discharged with AIS (ICD-10-CM I63*) as the principal diagnosis. Survival analysis with Weibull accelerated failure time regression was used to examine variables associated with hospital readmission. In 2019, 273,811 of 285,451 AIS patients survived their initial hospitalization. Of these, 60,831 (22.2%) were readmitted within 2019. Based on Kaplan Meyer analysis, readmission rates were 9.7% within 30 days and 30.5% at 1 year following initial discharge. The most common causes of readmissions were stroke and post stroke sequalae (25.4% of 30-day readmissions, 15.0% of readmissions between 30-364 days), followed by sepsis (10.3% of 30-day readmissions, 9.4% of readmissions between 30-364 days), and acute renal failure (3.2% of 30-day readmissions, 3.0% of readmissions between 30-364 days). After adjusting for multiple patient and hospital-level characteristics, patients at increased risk of readmission were older (71.6 vs. 69.8 years, p<0.001) and had longer initial lengths of stay (7.6 vs. 6.2 day, p<0.001). They more often had modifiable comorbidities, including vascular risk factors (hypertension, diabetes, atrial fibrillation), depression, epilepsy, and drug abuse. Social determinants associated with increased readmission included living in an urban (vs. rural) setting, living in zip-codes with the lowest median income, and having Medicare insurance. All factors were significant at p<0.001. Unplanned hospital readmissions following AIS were high, with the most common reasons for readmission being recurrent stroke and post stroke sequalae, followed by sepsis and acute renal failure. These findings suggest that efforts to reduce readmissions should focus on optimizing secondary stroke and infection prevention, particularly among older socially disadvantaged patients.

Cost-effectiveness of tenecteplase versus alteplase for acute ischemic stroke.

INTRODUCTION: Alteplase is widely used as an intravenous thrombolytic drug in acute ischemic stroke (AIS). Recently however, tenecteplase, a modified form of tissue plasminogen activator, has been shown to increase early recanalization rate and has proven to be non-inferior with a similar safety profile compared to alteplase. This study aims to evaluate the cost-effectiveness of 0.25 mg/kg tenecteplase versus 0.9 mg/kg alteplase for intravenous thrombolysis in AIS patients from the Dutch healthcare payer perspective. METHODS: A Markov decision-analytic model was constructed to assess total costs, total quality-adjusted life year (QALY), an incremental cost-effectiveness ratio, and incremental net monetary benefit (INMB) of two treatments at willingness-to-pay (WTP) thresholds of €50,000/QALY and €80,000/QALY over a 10-year time horizon. One-way sensitivity analysis, probabilistic sensitivity analysis, and scenario analysis were conducted to test the robustness of results. Clinical data were obtained from large randomized controlled trials and real-world data. RESULTS: Treatment with tenecteplase saved €21 per patient while gaining 0.05 QALYs, resulting in INMB of €2381, clearly rendering tenecteplase cost-effective compared to alteplase. Importantly, tenecteplase remained the cost-effective alternative in all scenarios, including AIS patients due to large vessel occlusion (LVO). Probabilistic sensitivity analysis proved tenecteplase to be cost-effective with a 71.0% probability at a WTP threshold of €50,000/QALY. CONCLUSIONS: Tenecteplase treatment was cost-effective for all AIS patients (including AIS patients with LVO) compared to alteplase. The finding supports the broader use of tenecteplase in acute stroke care, as health outcomes improve at acceptable costs while having practical advantages, and a similar safety profile.

Food Insecurity and Perceived Financial Stress are Associated with Cost-related Medication Non-adherence in Stroke.

OBJECTIVE: To determine whether food insecurity and perceived financial stress contribute to cost-related medication non-adherence (CRN) in stroke. METHODS: We conducted a retrospective study of adult stroke survivors in the National Health Interview Survey (2014-2018). Weighted prevalence of food insecurity, perceived financial stress, and CRN by age was calculated. Multiple logistic regression was conducted between food insecurity or perceived financial stress and CRN, adjusting for demographic and clinical variables. RESULTS: Prevalence of food insecurity, perceived financial stress, and CRN respectively were 38%, 75%, and 26% (age 18-44), 38%, 76%, and 21% (age 45-64) and 17%, 43%, and 6% (age≥ 65). Food insecurity and perceived financial stress respectively were associated with CRN in stroke survivors aged 45-64 [odds ratio (95% CI) 1.35 (1.18-1.54) and 1.44 (1.29-1.61)] and age ≥ 65 [1.77 (1.52-2.06) and 1.51 (1.37-1.67)]. CONCLUSION: Food insecurity and perceived financial stress are prevalent in stroke survivors and associated with CRN.

Guideline-Directed Low-Density Lipoprotein Cholesterol Management After Acute Ischemic Stroke: Findings from a National Health Care Service.

Patients with ischemic stroke are at high risk for future cardiovascular events and should be treated intensively with lipid-modifying agents. Combination lipid-lowering therapies are often needed to achieve updated guideline-directed treatment goals. However, real-world data on intensification of lipid-lowering therapies and attainment of low-density lipoprotein cholesterol (LDL-C) targets early after ischemic stroke are limited. We extracted data from the largest healthcare provider in Israel on patients hospitalized with acute ischemic stroke between January 2020 and February 2022. Included were 3,027 patients surviving ≥1 year after stroke, with documented LDL-C levels and lipid-lowering medications at 2 time periods (0 to 3 months and 6 to 12 months after discharge). Participants were classified according to preexisting stroke and/or coronary artery disease. The use of combination lipid-lowering therapy (ezetimibe and/or proprotein convertase subtilisin/kexin type 9 [monoclonal antibodies] inhibitor plus statin) in the study population increased between the 2 timepoints from 3.6% to 5.1%, reaching 10.5% in those with previous coronary artery disease and stroke. LDL-C levels <70 and <55 mg/100 ml were attained by 42.3% and 22.9% of patients early after hospitalization, and in 49.5% and 27.1% during 6 to 12 months after hospitalization, respectively. Attainment of guideline-recommended LDL-C goals was higher in patients treated with combination lipid-lowering therapies and in those with preexisting cardiovascular disease. In conclusion, despite the advances in drug development and the availability of several mechanisms to lower cholesterol levels, the attainment of guideline-recommended LDL-C targets after acute ischemic stroke is suboptimal. Intensification of treatment with combination lipid-lowering therapies after hospitalization is uncommonly performed in clinical practice, even in those with preexisting cardiovascular disease.

Patterns and outcomes of weekend admission for acute ischemic stroke.

BACKGROUND AND OBJECTIVES: The "weekend effect" describes worse care delivery during off-hours or weekends and has been demonstrated in multiple sub-specialties. Off-hours care for acute ischemic stroke (AIS) has been associated with poorer outcomes. However, there is less data about the "weekend effect" on endovascular thrombectomy (ET) outcomes. METHODS: We used Medicare 100% sample datasets and included all AIS admissions from 2018-2019, using validated International Classification of Diseases, 10th Revision, Clinical Modification codes to identify AIS and comorbidities. Medicare provides the date of admission for all hospitalizations, and the day of the week was determined and assigned to weekend (Saturday or Sunday) or weekday (Monday through Friday). We defined 3 major outcomes: inpatient mortality, discharge home (vs. other destination), and 30-day mortality. RESULTS: Among 471427 AIS admissions,13.0% and 12.9% of all AIS admissions occurred on a Saturday and Sunday, respectively, less than the expected 14.3% occurring on any given day (p-value <0.0001). AIS admissions on a weekend were less likely to receive IV thrombolysis (13.6% on Saturday and 12.9% on Sunday) and ET (13.1% on Saturday and 13.2% on Sunday), p-value <0.0001. Among all AIS admissions, weekend admission was associated with worse outcomes, including higher odds of inpatient mortality (adjusted OR 1.04 [95% CI 1.01-1.08, p<0.0001]), lower odds of discharge home (0.94 [0.93-0.96, p<0.0001]), and higher odds of 30-day mortality (1.06 [1.04-1.08, p<0.0001]). However, among AIS patients treated with ET, there was no association of weekend admission with outcomes. CONCLUSIONS: In this national and contemporary dataset, we observed that the proportion of thrombolysis and ET cases was less over the weekend, and outcomes (inpatient mortality, 30-day mortality and odds of discharge home) were worse overall. We did not observe this association among AIS patients undergoing ET on a weekend vs. weekday.

Neuroprotective Strategies for Stroke by Natural Products: Advances and Perspectives.

Cerebral ischemic stroke is a disease with high prevalence and incidence. Its management focuses on rapid reperfusion with intravenous thrombolysis and endovascular thrombectomy. Both therapeutic strategies reduce disability, but the therapy time window is short, and the risk of bleeding is high. Natural products (NPs) have played a key role in drug discovery, especially for cancer and infectious diseases. However, they have made little progress in clinical translation and pose challenges to the treatment of stroke. Recently, with the investigation of precise mechanisms in cerebral ischemic stroke and the technological development of NP-based drug discovery, NPs are addressing these challenges and opening up new opportunities in cerebral stroke. Thus, in this review, we first summarize the structure and function of diverse NPs, including flavonoids, phenols, terpenes, lactones, quinones, alkaloids, and glycosides. Then we propose the comprehensive neuroprotective mechanism of NPs in cerebral ischemic stroke, which involves complex cascade processes of oxidative stress, mitochondrial damage, apoptosis or ferroptosis-related cell death, inflammatory response, and disruption of the blood-brain barrier (BBB). Overall, we stress the neuroprotective effect of NPs and their mechanism on cerebral ischemic stroke for a better understanding of the advances and perspective in NPs application that may provide a rationale for the development of innovative therapeutic regimens in ischemic stroke.