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.

Major bleed costs of atrial fibrillation patients treated with factor Xa inhibitor anticoagulants.

OBJECTIVE: To examine the healthcare economic burden of atrial fibrillation (AF) patients treated with factor Xa inhibitor (FXaI) anticoagulants who were hospitalized in the US with a major bleed (MB). METHODS: Adult AF patients treated with FXaIs and hospitalized with an MB were selected from MarketScan databases (1 January 2015-30 April 2018). Patients were grouped into cohorts based on type of MB: intracranial hemorrhage (ICH), gastrointestinal (GI), other types of MB. Healthcare costs in 2019 USD were evaluated for index hospitalizations and during a variable follow-up period in unadjusted and adjusted analyses. RESULTS: Of the overall AF patient population treated with FXaIs and hospitalized with an MB (n = 7,577), 9.9% had ICH (mean age: 77.9 years; 58% male), 55.9% had GI (mean age: 76.8 years; 52% male), and 34.2% had other types of MB (mean age: 74.4 years; 61% male). Mean index hospitalization costs for ICH, GI, and other type of MB were $54,163, $26,901, and $36,645, respectively; from adjusted analyses, patients with ICH vs. GI spent 1.6 more days in the hospital; mean cost was $15,630 higher. Patients with other types of MB vs. GI spent 0.6 more days in the hospital; mean cost was $5,859 higher. Index hospitalization cost in addition to total all-cause healthcare costs incurred in the follow-up period were $34,522 higher per ICH patient and $11,584 higher per other type of MB patient vs. a GI MB patient. LIMITATIONS: Since this study was a retrospective observational study using a claims database analysis, a causal relationship between treatment with FXaIs and MB events cannot be established. CONCLUSIONS: Although all of the evaluated MB types were associated with high hospitalization costs, ICH was associated with the most substantial short- and long-term healthcare economic burden.

Evaluation of the Incremental Healthcare Economic Burden of Patients with Atrial Fibrillation Treated with Direct-Acting Oral Anticoagulants and Hospitalized for Major Bleeds in the USA.

INTRODUCTION: Direct-acting oral anticoagulants (DOACs) are associated with risk of major bleeding. This study evaluated the incremental healthcare economic burden of patients with atrial fibrillation (AF) treated with DOACs and hospitalized with a major bleed (MB). METHODS: Adult patients with AF treated with DOACs and hospitalized with MB or no MB hospitalizations during January 1, 2015-April 30, 2018 were extracted from MarketScan claims databases. The index date was defined as the first MB hospitalization for patients with MB and a random date during DOAC usage for patients without MB. Healthcare resource utilization and costs were evaluated for index hospitalizations of patients with MB and during the 6-month period prior to index dates and a variable follow-up period of 1-12 months for both patients with and those without MB. Multivariable regression analyses were performed to evaluate the incremental burden of MB vs. non-MB status on all-cause hospital days and healthcare costs. RESULTS: Of the overall AF patient population using DOACs (N = 152,305), 7577 (5.0%) had a hospitalization for MB. Greater proportions of those who had an MB hospitalization were older and female compared to patients without MB (mean age 76.1 vs. 70.1 years; 44.1% vs. 40.5% female, respectively). For index MB hospitalizations, mean length of stay (LOS) was 5.3 days and cost was $32,938. In adjusted analyses, patients with MB had 3.6 more hospital days, $10,609 higher inpatient cost, $9613 higher outpatient medical cost, and $18,910 higher total healthcare costs for all causes per patient during follow-up (all p < 0.001). Including index MB hospitalization costs in the follow-up, all-cause total adjusted healthcare costs were almost two times higher for patients with vs. without MB ($96,590 vs. $49,091, p < 0.001). CONCLUSIONS: Among a large US nationally representative sample of patients with AF treated with DOACs, the cost of MB hospitalization was substantial. Furthermore, healthcare costs following MB events were nearly 40% higher compared to those of patients with AF without an MB.

The burden of illness of hepatorenal syndrome (HRS) in the United States: a retrospective analysis of electronic health records.

OBJECTIVES: Hepatorenal Syndrome (HRS) is characterized by renal failure in patients with advanced chronic liver disease (CLD) and is the leading cause of hospitalizations in CLD. This study examines the clinical and economic burden, outcomes, and unmet need of HRS treatment in US hospitals. METHOD: A retrospective cohort study was conducted based on a large electronic health records database (Cerner HealthFacts) with records for hospitalized HRS patients from January 2009-June 2015. Demographics, clinical characteristics, treatment patterns, and economic outcomes were analyzed. Prognostic indicators of cirrhosis, kidney injury, end-stage liver disease, and acute-on-chronic liver failure were used to determine mortality risk. RESULTS: A total of 2,542 patients hospitalized with HRS were identified (average age = 57.9 years, 61.8% males, 74.2% Caucasian), with an average total hospital charge of $91,504 per patient and a mean length of stay (LOS) of 30.5 days. The mortality rate was 36.9% with 8.9% of patients discharged to hospice. Of all patients, 1,660 patients had acute kidney injury, 859 with Stage 3 disease, and 26.7% had dialysis. The 30-day readmission rate was 33.1%, 41% of which were unplanned. Nearly one-third of study patients had commercial insurance (30.2%), followed by Medicare (29.9%); hospital charges varied by LOS, receipt of dialysis, and discharge status. Regression analysis demonstrated that HRS costs are associated with LOS, dialysis, and hospital mortality. CONCLUSION: HRS is associated with poor outcomes and high hospital costs. Analysis of HRS cost drivers demonstrated an unmet need for additional treatment options to improve outcomes in this patient population.

Intravenous Acetaminophen May Be Associated with Reduced Odds of 30-Day Readmission after Total Knee Arthroplasty.

The purpose of this study was (1) to evaluate 30-day readmission rates in total knee arthroplasty (TKA) patients who either received intravenous (IV) or oral (PO) acetaminophen (APAP) perioperatively and (2) to extrapolate the potential annual cost savings on the national level. This was a review of 190,691 TKA recipients between the years 2012 and 2015 who received either IV (n = 56,475) or PO APAP (n = 134,216). All-cause readmissions that occurred between patient discharge and 30 days postdischarge were recorded. Continuous and categorical variables were evaluated using t-test and chi-square test, respectively. A logistic regression analysis was conducted to assess the effect of IV APAP on 30-day readmission. We also performed a literature review on 30-day readmission rates and risk prediction tools for TKA and correlated these with our findings. In addition, we extrapolated potential cost savings on the national level. The readmission rate was 0.04% in the IV and 0.14% in the PO APAP cohort (69% decreased risk; odds ratio = 0.31; 95% confidence interval = 0.20-0.47; p < 0.001). The readmission rate in this patient population appears to be markedly lower, when compared with previous reports. This reduction in readmissions may potentially result in $160 million savings per year. The use of IV APAP in TKA patients resulted in lower readmission rates, which may be valuable in clinical decision making by surgeons and health care administrators looking to lower costs of care.

Reduced length of stay and hospitalization costs among inpatient hysterectomy patients with postoperative pain management including IV versus oral acetaminophen.

OBJECTIVE: To compare the outcomes of hysterectomy patients who received standard pain management including IV acetaminophen (IV APAP) versus oral APAP. METHODS: We performed a retrospective analysis of the Premier Database (January 2012 to September 2015) comparing hysterectomy patients who received postoperative pain management including IV APAP to those who received oral APAP starting on the day of surgery and continuing up to the third post-operative day, with no exclusions based on additional pain management. We compared the groups on length of stay (LOS), hospitalization costs, and average daily morphine equivalent dose (MED). The quarterly rate of IV APAP use for all hospitalizations by hospital was used as an instrumental variable in two-stage least squares regressions also adjusting for patient demographics, clinical risk factors, and hospital characteristics. RESULTS: We identified 22,828 hysterectomy patients including 14,811 (65%) who had received IV APAP. Study subjects averaged 50 and 52 years of age, respectively in the IV APAP and oral APAP cohorts and were predominantly non-Hispanic Caucasians (≥60% in both cohorts). Instrumental variable models found IV APAP associated with 0.8 days shorter hospitalization (95% CI: -0.92 to -0.68, p<0.0001) and $2,449 lower hospitalization costs (95% CI: -$2,902 to -$1,996, p<0.0001). Average daily MED trended lower without statistical significance (-1.41 mg, 95% CI: -3.43 mg to 0.61 mg, p = 0.17). CONCLUSIONS: Compared to oral APAP, managing post-hysterectomy pain with IV APAP is associated with shorter LOS and lower total hospitalization costs.

Hospitalization costs and resource allocation in cholecystectomy with use of intravenous versus oral acetaminophen.

OBJECTIVE: To evaluate intravenous (IV) acetaminophen (APAP) vs oral APAP use as adjunctive analgesics in cholecystectomy patients by comparing associated hospital length of stay (LOS), hospital costs, opioid use, and rates of nausea/vomiting, respiratory depression, and bowel obstruction. METHODS: We conducted a retrospective analysis of the Premier Database (January 2012 to September 2015) including cholecystectomy patients who received either IV APAP or oral APAP. Differences in LOS, hospitalization costs, mean daily morphine equivalent dose (MED), and potential opioid-related adverse events were estimated. Multivariable logistic regression was performed for the binary outcomes and instrumental variable regressions, using the quarterly rate of IV APAP use for all hospitalizations by hospital as the instrument in two-stage least squares regressions for continuous outcomes. Models were adjusted for patient demographics, clinical risk factors, and hospital characteristics. RESULTS: Among 61,017 cholecystectomy patients, 31,133 (51%) received IV APAP. Subjects averaged 51 and 57 years of age, respectively, in the IV and oral APAP cohorts. In the adjusted models, IV APAP was associated with 0.42 days shorter LOS (95% CI = -0.58 to -0.27; p < .0001), $1,045 lower hospitalization costs (95% CI = -$1,521 to -$569; p < .0001), 2 mg lower average daily MED (95% CI = -3 mg to -0.9 mg; p = .0005), and lower rates of respiratory depression (odds ratio [OR] = 0.89, 95% CI = 0.82-0.97; p = .006), and nausea and vomiting (OR = 0.86, 95% CI = 0.86-0.86; p < .0001). CONCLUSIONS: In patients having cholecystectomy, the addition of IV APAP to perioperative pain management is associated with shorter LOS, lower costs, reduced opioid use, and less frequent nausea/vomiting and respiratory depression compared to oral APAP. These findings should be confirmed in a prospective study comparing IV and oral APAP.

Comparative Analysis of Inpatient Costs for Obstetrics and Gynecology Surgery Patients Treated With IV Acetaminophen and IV Opioids Versus IV Opioid-only Analgesia for Postoperative Pain.

BACKGROUND: Recovery from obstetrics and gynecology (OB/GYN) surgery, including hysterectomy and cesarean section delivery, aims to restore function while minimizing hospital length of stay (LOS) and medical expenditures. OBJECTIVE: Our analyses compare OB/GYN surgery patients who received combination intravenous (IV) acetaminophen and IV opioid analgesia with those who received IV opioid-only analgesia and estimate differences in LOS, hospitalization costs, and opioid consumption. METHODS: We performed a retrospective analysis of the Premier Database between January 2009 and June 2015, comparing OB/GYN surgery patients who received postoperative pain management with combination IV acetaminophen and IV opioids with those who received only IV opioids starting on the day of surgery and continuing up to the second postoperative day. We performed instrumental variable 2-stage least-squares regressions controlling for patient and hospital covariates to compare the LOS, hospitalization costs, and daily opioid doses (morphine equivalent dose) of IV acetaminophen recipients with that of opioid-only analgesia patients. RESULTS: We identified 225 142 OB/GYN surgery patients who were eligible for our study of whom 89 568 (40%) had been managed with IV acetaminophen and opioids. Participants averaged 36 years of age and were predominantly non-Hispanic Caucasians (60%). Multivariable regression models estimated statistically significant differences in hospitalization cost and opioid use with IV acetaminophen associated with $484.4 lower total hospitalization costs (95% CI = -$760.4 to -$208.4; P = 0.0006) and 8.2 mg lower daily opioid use (95% CI = -10.0 to -6.4), whereas the difference in LOS was not significant, at -0.09 days (95% CI = -0.19 to 0.01; P = 0.07). CONCLUSION: Compared with IV opioid-only analgesia, managing post-OB/GYN surgery pain with the addition of IV acetaminophen is associated with decreased hospitalization costs and reduced opioid use.

The burden of hepatorenal syndrome among commercially insured and Medicare patients in the United States.

BACKGROUND: This study evaluated the characteristics, healthcare resource utilization (HCRU), and costs, from the payer perspective, of hepatorenal syndrome (HRS) patients covered by commercial and Medicare insurance. Mortality was assessed as a secondary outcome. METHODS: Patients were identified from claims databases of commercially insured patients (OptumHealth Care Solutions Inc.) in 1998-2014 and Medicare beneficiaries in 2009-2013 (5% Standard Analytic Files). At the time of their first inpatient admission ("index date") with an HRS diagnosis (ICD-9 code 572.4), commercially insured patients must be aged 18-64 and Medicare patients must be aged 65 and older. RESULTS: A total of 784 commercially insured and 1061 Medicare HRS patients met the sample selection criteria. Patients were disproportionately male (commercial: 63.0%; Medicare: 57.9%) with a mean age of 54.1 among commercially insured and 74.1 among Medicare patients. Within the first 30 days, the average hospital length of stay (LOS) was 12.3 days among commercially insured and 10.8 days among Medicare patients. Based on Kaplan-Meier analyses, 36% of commercially insured and 26% of Medicare patients were readmitted within the next 30 days. During follow-up, many patients received dialysis (commercial: 33.0%; Medicare: 22.1%) or liver transplant (commercial: 10.7%; Medicare: 1.6%). Average costs within the 90 day follow-up were $157,665 for commercially insured and $48,322 for Medicare patients, with 68.3% and 78.3% of the costs incurred within the first 30 days. The primary cost driver was inpatient visits (commercial: 90.3% of costs; Medicare: 83.1% of costs), with differences between the populations consistent with lower mortality, higher dialysis rates, and higher transplant rates (both liver and kidney) among the commercially insured. Using US population and prevalence statistics, these results suggest that HRS imposes an annual total direct medical cost burden of approximately $3.0-$3.8 billion to payers over the period. CONCLUSIONS: HRS imposes a significant economic burden.

Comparative analysis of length of stay, hospitalization costs, opioid use, and discharge status among spine surgery patients with postoperative pain management including intravenous versus oral acetaminophen.

BACKGROUND: Recovery from spine surgery is oriented toward restoring functional health outcomes while reducing resource use. Optimal pain management is a key to reaching these objectives. We compared outcomes of spine surgery patients who received standard pain management including intravenous (IV) acetaminophen (APAP) vs. oral APAP. METHODS: We performed a retrospective analysis of the Premier database (January 2012 to September 2015) comparing spine surgery patients who received pain management with IV APAP to those who received oral APAP, with no exclusions based on additional pain management. We performed multivariable logistic regression for the discharge and all cause 30-day readmission to the same hospital outcomes and instrumental variable regressions using the quarterly rate of IV APAP use for all hospitalizations by hospital as the instrument in two-stage least squares regressions for length of stay (LOS), hospitalization costs, and average daily morphine equivalent dose (MED) outcomes. Models adjusted for age, gender, race, admission type, 3M All Patient Refined Diagnosis Related Group severity of illness and risk of mortality, hospital size, and indicators for whether the hospital was an academic center and whether it was urban or rural. RESULTS: We identified 112,586 spine surgery patients with 51,835 (46%) having received IV APAP. Subjects averaged 57 and 59 years of age respectively in the IV APAP and oral APAP cohorts and were predominantly non-Hispanic Caucasians and female. In our adjusted models, IV APAP was associated with 0.68 days shorter LOS (95% CI: -0.76 to -0.59, p < .0001), $1175 lower hospitalization costs (95% CI: -$1611 to -$739, p < .0001), 13 mg lower average daily MED (95% CI: -14 mg to -12 mg, p < .0001), 34% lower risk of discharge to a skilled nursing facility (95% CI: 0.63 to 0.69, p < .0001), and 13% less risk of 30-day readmission (95% CI: 0.73 to 1.03). CONCLUSIONS: Compared to oral APAP, managing post-spine-surgery pain with IV APAP is associated with less resource use, lower costs, lower doses of opioids, and improved discharge status.