Costs and Healthcare Resource Utilization Associated with Idarucizumab or Andexanet Alfa Oral Anticoagulant Reversal in Patients Hospitalized with Life-Threatening Bleeds.

Purpose: To assess costs and healthcare resource utilization (HCRU) associated with the use of idarucizumab for the reversal of dabigatran and andexanet alfa for the reversal of direct oral Factor Xa inhibitors. Methods: This retrospective study utilizing Premier Healthcare Database (PHD) included patients aged ≥18 years on direct oral anticoagulants (DOACs) who experienced life-threatening bleeds, discharged from the hospital during 5/1/2018-6/30/2019, and received idarucizumab or andexanet alfa. Inverse of treatment probability weighting (IPTW) method was used to balance patient and clinical characteristics between treatment cohorts. Results: Idarucizumab patients were older than andexanet alfa patients (median age 81 vs 77 years; p < 0.001), and less likely to experience intracranial hemorrhage (ICH) (37.1%vs 73.8%; p = 0.001). After IPTW adjustment, idarucizumab patients incurred lower mean total hospital costs ($30,413 ± $33,028 vs $44,477 ± $30,036; p < 0.001),and mean intensive care unit (ICU) cost ($25,114 ± $30,433 vs $43,484 ± $29,335; p < 0.001). Conclusions: Anticoagulant reversal therapy with idarucizumab was associated with significantly lower adjusted mean total hospital and ICU costs compared with andexanet alfa. However, a higher prevalence of ICH bleeds was noted in the andexanet alfa group. Trial Registration: Not applicable.

Cost-effectiveness of andexanet alfa versus four-factor prothrombin complex concentrate for the treatment of oral factor Xa inhibitor-related intracranial hemorrhage in the US.

AIM: To conduct a cost-effectiveness analysis (CEA) on the use of andexanet alfa for the treatment of factor Xa inhibitor-related intracranial hemorrhage (ICH) from the US third-party payer and societal perspectives. METHODS: CEA compared andexanet alfa to prothrombin complex concentrate for the treatment of patients receiving factor Xa inhibitors admitted to hospital inpatient care with an ICH. The model comprised two linked phases. Phase 1 utilized a decision tree to model the acute treatment phase (admission of a patient with ICH into intensive care for the first 30 days). Phase 2 modeled long-term costs and outcomes using three linked Markov models comprising the six health states defined by the modified Rankin score. RESULTS: The analysis showed that the strategy of using andexanet alfa for the treatment of factor Xa inhibitor-related ICH is cost-effective, with incremental cost-effectiveness per quality-adjusted life-year gained of $35,872 from a third-party payer perspective and $40,997 from a societal perspective over 20 years. LIMITATIONS: (1) Absence of head-to-head trials comparing therapies included in the economic model, (2) lack of comparative long-term data on treatment efficacy, and (3) bias resulting from the study designs of published literature. CONCLUSION: Given these results, the use of andexanet alfa for the reversal of anticoagulation in patients with factor Xa inhibitor-related ICH may improve quality of life and is likely to be cost-effective in a US context.

Retrospective Assessment of Desmopressin Effectiveness and Safety in Patients With Antiplatelet-Associated Intracranial Hemorrhage.

OBJECTIVE: Current international guidelines offer a conditional recommendation to consider a single dose of IV desmopressin (DDAVP) for antiplatelet-associated intracranial hemorrhage based on low-quality evidence. We provide the first comparative assessment analyzing DDAVP effectiveness and safety in antiplatelet-associated intracranial hemorrhage. DESIGN: Retrospective chart review. SETTING: Single tertiary care academic medical center. PATIENTS: Adult patients taking at least one antiplatelet agent based on presenting history and documented evidence of intracranial hemorrhage on cerebral CT scan were included. Patients were excluded for the following reasons: repeat cerebral CT scan not performed within the first 24 hours, noncomparative repeat cerebral CT scan, chronic anticoagulation, administration of fibrinolytic medications, concurrent ischemic stroke, and neurosurgical intervention. In total, 124 patients were included, 55 received DDAVP and 69 did not. INTERVENTIONS: DDAVP treatment at recognition of antiplatelet-associated intracranial hemorrhage versus nontreatment. MEASUREMENTS AND MAIN RESULTS: Primary effectiveness outcome was intracranial hemorrhage expansion greater than or equal to 3 mL during the first 24 hospital hours. Primary safety outcomes were the largest absolute decrease from baseline serum sodium during the first 3 treatment days and new-onset thrombotic events during the first 7 days. DDAVP was associated with 88% decreased likelihood of intracranial hemorrhage expansion during the first 24 hours ([+] DDAVP, 10.9% vs [-] DDAVP, 36.2%; p = 0.002; odds ratio [95% CI], 0.22 [0.08-0.57]). Largest median absolute decrease from baseline serum sodium ([+] DDAVP, 0 mEq/L [0-5 mEq/L] vs [-] DDAVP, 0 mEq/L [0-2 mEq/L]; p = 0.089) and thrombotic events ([+] DDAVP, 7.3% vs [-] DDAVP, 1.4%; p = 0.170; odds ratio [95% CI], 5.33 [0.58-49.16]) were similar between groups. CONCLUSIONS: DDAVP was associated with a decreased likelihood of intracranial hemorrhage expansion during the first 24 hours. DDAVP administration did not significantly affect serum sodium and thrombotic events during the study period.

Outcomes and Costs of Patients Admitted to the ICU Due to Spontaneous Intracranial Hemorrhage.

OBJECTIVES: Spontaneous intracranial hemorrhage, including subarachnoid hemorrhage and intracerebral hemorrhage, is associated with significant morbidity and mortality. Although many of these patients will require ICU admission, little is known regarding their outcomes and the costs incurred. We evaluated this population in order to identify outcomes and cost patterns. DESIGN: Retrospective cohort analysis of a health administrative database. SETTING: Two ICUs within a single hospital system. PATIENTS: Eight-thousand four-hundred forty-seven patients admitted to ICU from 2011 to 2014, of whom 332 had a diagnosis of spontaneous intracranial hemorrhage. Control patients were defined as randomly selected age, sex, and comorbidity index-matched nonintracranial hemorrhage ICU patients (1:4 matching ratio). INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Mean age of ICU intracranial hemorrhage patients was 60.1 years, and 120 (36.1%) died prior to discharge. Intracranial hemorrhage was associated with a mean total cost of $75,869, compared with $52,471 in control patients (p < 0.01). Mean cost per survivor of intracranial hemorrhage patients was $118,813. Subarachnoid hemorrhage was associated with significantly higher mean total costs than intracerebral hemorrhage ($92,794 vs $53,491; p < 0.01) and higher mean cost per day ($4,377 vs $3,604; p < 0.01). Patients with intracranial hemorrhage who survived to hospital discharge were significantly costlier than decedents ($100,979 vs $30,872; p < 0.01). Intracranial hemorrhage associated with oral anticoagulant use had a mean total cost of $152,373, compared with $66,548 in nonoral anticoagulant intracranial hemorrhage (p < 0.01). CONCLUSIONS: Patients admitted to ICU with intracranial hemorrhage have high costs and high mortality, leading to elevated cost per survivor. Subarachnoid hemorrhage patients incur greater costs than intracerebral hemorrhage patients, and oral anticoagulant-associated intracerebral hemorrhage is particularly costly. Our findings provide novel information regarding financial impact of this common ICU population.

Apneic oxygenation is associated with a reduction in the incidence of hypoxemia during the RSI of patients with intracranial hemorrhage in the emergency department.

Critically ill patients undergoing emergent intubation are at risk of oxygen desaturation during the management of their airway. Patients with intracranial hemorrhage (ICH) are particularly susceptible to the detrimental effects of hypoxemia. Apneic oxygenation (AP OX) may be able to reduce the occurrence of oxygen desaturation during the emergent intubation of these patients. We sought to assess the effect AP OX on oxygen desaturation during the rapid sequence intubation (RSI) of patients with ICH in the emergency department (ED). We prospectively collected data on all patients intubated in an urban academic ED over the 2-year period from July 1, 2013 to June 30, 2015. Following each intubation, the operator completed a standardized continuous quality improvement (CQI) data form, which included information on patient, operator and intubation characteristics. Operators recorded data on the use of AP OX, the oxygen flow rate used for AP OX, and the starting and lowest saturations during intubation. Adult patients with ICH who underwent RSI by emergency medicine (EM) residents were included in the analyses. The primary outcome variable was any oxygen saturation <90 % during the intubation. We performed a backward stepwise multivariate logistic regression analysis to identify variables associated with oxygen desaturation. The primary independent variable of interest was the use of AP OX during the intubation. Inclusion criteria for the study was met by 127 patients. AP OX was used in 72 patients (AP OX group) and was not used in 55 patients (NO AP OX group). The incidence of desaturation was 5/72 (7 %) in the AP OX group and was 16/55 (29 %) in the NO AP OX group. In the multivariate logistic regression analysis the use of AP OX was associated with a reduced odds of desaturation (aOR 0.13; 95 % CI 0.03-0.53). Patients with ICH who received AP OX during RSI in the ED were seven times less likely to have an oxygen saturation of <90 % during the intubation compared to patients who did not receive AP OX. AP OX is a simple intervention that may minimize the risk of oxygen desaturation during the RSI of patients with ICH.

Laboratory assessment of warfarin reversal with global coagulation tests versus international normalized ratio in patients with intracranial bleeding.

We assess the in-vivo relationship between international normalized ratio (INR) and global coagulation tests in patients with life-threatening bleeding who received prothrombin complex concentrate (PCC) for warfarin reversal. This was a prospective pilot study in adult patients with intracranial bleeding related to anticoagulation with warfarin. Thromboelastography (TEG), thrombin generation parameters and INR were assessed at baseline, 30  min, 2 and 24  h after PCC. Changes in laboratory parameters and relationship between INR and global coagulation tests were assessed over time. Eight patients mean [standard deviation (SD)] age 72 (16) were included and received mean (SD) dose of PCC 24 (5) units/kg. Four patients died during the study, all with INR values more than 1.5 thirty minutes after PCC. Mean (SD) INR was 3.0 (1.3) and decreased significantly to 1.8 (0.48) thirty minutes after PCC (P < 0.01). Baseline endogenous thrombin potential and thrombin peak were 890  nmol/min and 123  nmol and increased significantly to 1943  nmol/min (P < 0.01) and 301  nmol (P < 0.01) 30  min after PCC administration. Reaction (R)-time decreased significantly (P = 0.02), and maximum amplitude and overall coagulation index (CI) significantly increased during treatment (P < 0.01, respectively). Thrombin generation and TEG values corrected after PCC administration; however, INR did not fully correct. Patients that died tended to be older with prolonged INR values across the study period. INR and TEG values correlated well with thrombin generation before administration of PCC, but this relationship was lost afterward.

Recombinant factor VIIa and the patient with neurologic bleeding: separating fact from fiction.

Notwithstanding its limited Food and Drug Administration-approved indications, rFVIIa has rapidly gained widespread use for the treatment of a variety of hemorrhagic conditions, including intracranial bleeding from spontaneous, traumatic, surgical, and coagulopathic causes. Although it appears that the drug only minimally increases the risk of thromboembolic events, its efficacy remains in question. The idea of finding a universal cure for hemorrhage in a medication bottle remains highly appealing, but enthusiasm for the concept is no replacement for evidence. Neuroscience nurses, who are the interface between patients and rFVIIa, need to balance hope and hype until the facts are all in.

Coagulation factor VIIa (recombinant) in nonhemophilic patients requiring neurosurgery.

PURPOSE: The clinical outcomes, safety, and use of resources associated with the administration of factor VIIa (recombinant) to nonhemophilic patients requiring neurosurgery were evaluated. METHODS: An interdisciplinary group created guidelines for the pharmacy and therapeutics committee for the unlabeled use of factor VIIa (recombinant). Nonhemophilic patients were eligible to receive the agent without approval from the hematology-coagulation service if they had an intracranial hemorrhage (ICH), were undergoing an emergency neurosurgical procedure, and had coagulopathy. A standard single dose of 40 microg/kg was recommended for these patients. Data were prospectively collected between March 2004 and March 2006 for all neurological surgery patients receiving factor VIIa (recombinant). RESULTS: A total of 92 nonhemophilic patients received single doses of factor VIIa (recombinant) under the guidelines during the two-year study period. The majority of patients had a baseline International Normalized Ratio (INR) of >2, underwent emergency neurosurgical procedures, and had an intracranial hemorrhage. All guideline criteria for indication and approval were followed for 48 patients. Eighty-seven patients received concomitant treatment for reversal of anticoagulation. A significant correction in the baseline INR after administration of factor VIIa (recombinant) was noted (p < 0.0001). Five patients experienced adverse events. Implementation of the guidelines decreased the annual cost of factor VIIa (recombinant) by 46%. CONCLUSION: A protocol calling for administration of factor VIIa (recombinant) 40 microg/kg in nonhemophilic patients with coagulopathy and ICH led to a rapid and significant decrease in the INR, allowing for emergency surgical intervention. Few adverse events were detected in these patients, and none were deemed to be directly related to factor VIIa (recombinant).

Cost-effectiveness of antiplatelet agents in secondary stroke prevention: the limits of certainty.

UNLABELLED: Which of the available antiplatelet therapies should be preferred for secondary prevention of recurrent ischemic stroke has been contentious. OBJECTIVE: We applied the Duke Stroke Policy Model (DSPM) to reconsider this issue, paying particular attention to the degree of uncertainty in the estimates of their efficacy. The DSPM is a continuous-time simulation model of stroke development and outcome. METHODS: We modified the inputs to reflect the cost of the drugs aspirin (ASA), extended release dipyridamole/aspirin (DP/A) and clopidogrel (CLO), as well as their relative risk in preventing subsequent ischemic stroke in comparison with placebo (PBO). These relative risks were derived from published reports from the second European Stroke Prevention Study (ESPS-2) and Clopidogrel Versus Aspiring in Patients at Risk of Ischemic Events studies. Precision was addressed by applying bootstrapping to the above estimates of relative risk. The target population was 70-year-old men with nondisabling stroke. The outcome measures were quality-adjusted life-years (QALYs), costs, and costs per QALY. RESULTS: Results of Base Case Analysis: In large part because of its modest drug cost, ASA was cost-effective in comparison with PBO. DP/A tended to have improved outcomes, but at increased costs. CLO was dominated in the base case. RESULTS OF SENSITIVITY ANALYSIS: ASA and DP/A cannot be differentiated on a statistical basis alone. In probabilistic sensitivity analysis, CLO was rarely preferred. CONCLUSIONS: Either DP/A or ASA appear to be a good value in comparison with no treatment, but there is no clear winner between the two. In the absence of a definitive randomized trial, simulation modeling can help clarify the trade-offs between the various antiplatelet agents, but not beyond the constraints imposed by the imprecision in the estimates that can be obtained from the current evidence base.

[Preliminary study on outcome assessment system of treatment of stroke].

OBJECTIVE: In order to scientifically reflect the real efficacy of TCM treatment and to preliminarily establish a definitely valid and reliable assessment system of stroke treatment, with multi-dimensional outcome assessment indexes, including efficacy evaluation system of conventional western medicine, syndrome evaluation criteria in TCM and quality of life assessment system. METHODS: An integrative approach of cross-sectional survey and prospective follow-up was adopted. Two hundred and forty-five case-episodes of stroke patients were assessed by determining such parameters as nerve functional deficit scale, grading of total status of living ability, activity of daily living (ADL), TCM stroke criteria of diagnosing-treatment, TCM syndrome related symptoms/signs, Health Survey Questionnaire (Short form 36, SF-36), and index of quality of life (QOL), and their construction and relation were analyzed by such methods as multivariate relation, partial relation, linear regression, factor analysis, Cronbach's alpha coefficients, and the responsiveness estimation. RESULTS: The multi-dimensional assessment system of stroke treatment, containing 57 indexes with clarified constructions and classification, was created, and its validity and reliability confirmed after assessement. Various degrees of relationship were found between different TCM Syndromes and different domains of QOL. CONCLUSION: The assessment system of stroke treatment preliminarily created has satisfied reliability and validity. It could be expected to reflect the real efficacy of TCM treatment more inclusive and accurate. TCM Syndrome indexes are considered to be the factor related to both domains of mental and physical health, particularly with the former, therefore, to improve the TCM Syndrome would imply improvement of the mental health, physical health and QOL of the patients.