Eptacog Beta for Bleeding Treatment and Prevention in Congenital Hemophilia A and B With Inhibitors: A Review of Clinical Data and Implications for Clinical Practice.

OBJECTIVE: To review the pharmacology, dosing and administration, safety, clinical efficacy, and role of eptacog beta in the treatment of congenital hemophilia with inhibitors. DATA SOURCES: A literature search of PubMed (1966 to August 2021) was conducted using the keywords eptacog beta, recombinant FVII, and hemophilia. STUDY SELECTION AND DATA EXTRACTION: All relevant published articles and prescribing information on eptacog beta for the treatment of congenital hemophilia with inhibitors were reviewed. DATA SYNTHESIS: Eptacog beta is a novel recombinant activated factor VII (rVIIa) product that demonstrated efficacy in controlling bleeding and associated pain in patients with hemophilia A or B with inhibitors. Eptacog beta has limited Food and Drug Administration-approved and off-label indications compared with other bypassing agents (BPAs; activated prothrombin complex concentrates [aPCC; eptacog alfa]). Eptacog beta costs less than eptacog alfa, but still more than aPCCs. RELEVANCE TO PATIENT CARE AND CLINICAL PRACTICE: This review provides insight into the role of eptacog beta for treatment of congenital hemophilia with inhibitors and reviews important health system formulary considerations for available BPAs. CONCLUSIONS: Eptacog beta is more cost-effective than eptacog alfa and, as such, may become the preferred rVIIa formulary product. However, eptacog alfa availability remains necessary for the treatment of disorders where eptacog beta has limited data. aPCC should remain the first-line BPA for the treatment of bleeding in patients with inhibitors with no contraindications to use because of its equivocal efficacy and safety and in light of the magnitude of cost savings associated with this strategy.

Bleeding and Thrombotic Events During Extracorporeal Membrane Oxygenation for Postcardiotomy Shock.

BACKGROUND: Anticoagulation therapy management during venoarterial extracorporeal membrane oxygenation (ECMO) is particularly difficult in postcardiotomy shock patients given a significant bleeding risk. We sought to determine the effect of anticoagulation treatment on bleeding and thrombosis risk for postcardiotomy shock patients on ECMO. METHODS: We retrospectively reviewed patients who received ECMO for postcardiotomy shock from July 2007 through July 2019. Characteristics of patients who had bleeding and thrombosis were investigated, and risk factors were assessed by multilevel logistic regression. RESULTS: Of the 152 patients who received ECMO for postcardiotomy shock, 33 (23%) had 40 thrombotic events and 64 (45%) had 86 bleeding events. Predictors of bleeding were intraoperative packed red blood cell transfusion (odds ratio [OR] 1.05; 95% confidence interval [CI], 1.01 to 1.09), platelet transfusion (OR 1.10; 95% CI, 1.05 to 1.16), international normalized ratio (OR 1.18; 95% CI, 1.02 to 1.37), and activated partial thromboplastin time greater than 60 seconds (OR 2.32; 95% CI, 1.14 to 4.73). Predictors of thrombosis were anticoagulant use (OR 0.39; 95% CI, 0.19 to 0.79), surgical venting (OR 3.07; 95% CI, 1.29 to 7.31), hemoglobin (OR 1.38; 95% CI, 1.06 to 1.79), and central cannulation (OR 2.06; 95% CI, 1.03 to 4.11). The daily predicted probability of thrombosis was between 0.075 and 0.038 for patients who did not receive anticoagulation and decreased to between 0.030 and 0.013 for patients who received anticoagulation treatment at activated partial thromboplastin times between 25 and 80 seconds. CONCLUSIONS: Anticoagulation therapy can reduce thromboembolic events in postcardiotomy shock patients on ECMO, but bleeding risk may outweigh this benefit at activated partial thromboplastin times greater than 60 seconds.

Impact of heart failure drug therapy on rates of gastrointestinal bleeding in LVAD recipients: An INTERMACS analysis.

INTRODUCTION: Gastrointestinal bleeding (GIB) remains a common and vexing complication of left ventricular assist device (LVAD) support. Recent single-center analyses suggest that ACE inhibitors (ACEi)/angiotensin receptor blockers (ARB) and digoxin may prevent GIB in LVAD patients. Here we evaluate the effect of guideline-directed medical therapies (GDMT) for heart failure (HF) on rates of GIB through analysis of the INTERMACS registry database. METHODS: Thirteen thousand seven hundred thirty-two patients who received a continuous-flow LVAD and were on antiplatelet therapy and anticoagulation with warfarin after 3 months of pump support were included in the analysis. GIB events following implant were assessed based on receipt of ACEi/ARB, beta-blockers (BB), mineralocorticoid receptor antagonist (MRA), amiodarone, digoxin, loop diuretics, and phosphiesterase-5 inhibitors (PDE5). Backwards stepwise cox regression was used to control for confounding of each drug class on each other, as well as for clinical variables like age, gender, renal function, HF etiology, and device strategy. RESULTS: After 3 months of pump support medications used in LVAD patients were BB (65.0%), ACEi/ARB (51.7%), Amio (43.7%), MRA (37.9%), and loop diuretics (70.1%). In patients with available data, PDE and digoxin use were 18.2% and 16.9%, respectively. The overall incidence of GIB was 19.5% at 2 years of support. After adjustment for other clinical variables, loop diuretics (HR 1.274, p < 0.001) and PDE5 (HR 1.241, p < 0.001) use were associated with increased risk of GIB, while use of BB (HR 0.871, p = 0.006) was associated with lower risk of GIB. ACEi/ARB (HR 1.002, p = 0.971), Amio (HR 1.083, p = 0.106), AA (HR 0.967, p = 0.522) or digoxin (HR 1.087, p = 0.169) did not affect GIB rates on LVAD support (Figure). CONCLUSION: Despite recent reports, ACEi/ARB, MRA, Amio, and digoxin use does not appear to be associated with GIB during LVAD support. The heightened risk seen in those on loop diuretics may reflect venous congestion in these patients, while antiplatelet effects of PDE5 could drive the higher risk of GIB.

A reappraisal of the pharmacologic management of gastrointestinal bleeding in patients with continuous flow left ventricular assist devices.

Advancements in the design and functionality of continuous flow left ventricular assist devices (CF-LVADs), as well as a limited number of donor hearts, have resulted in an increased utilization of this therapy among advanced heart failure (HF) patients. Despite these advancements, gastrointestinal bleeding (GIB) remains a common complication after CF-LVAD implantation. The mechanism of GIB in these patients is complex and includes a combination of angiodysplasia, platelet dysfunction, acquired von Willebrand disease, and a variety of patient-specific factors including advanced age and history of GIB. Several pharmacotherapy options have been reported in the literature, though studies supporting the use of these agents are often small, retrospective reports. Within this review, we discuss the various pharmacologic agents, their proposed mechanisms of action, and the available literature pertaining to their effectiveness and tolerability. Additionally, we propose an evidence-based treatment algorithm, encompassing the updated literature, cost of therapy, medication side effects, and ease of administration.

Rethinking the Drug Distribution and Medication Management Model: How a New York City Hospital Pharmacy Department Responded to COVID-19.

Beginning in March 2020, New York City began the fight against coronavirus disease 2019. Health care workers were faced with a disease that led to significant morbidity and mortality with no proven therapies. As hospitals became inundated with patients and underwent rapid expansion of capacity, resources such as drugs, protective and medical equipment, and hospital staff became limited. Pharmacists played a critical role in the management of clinical care and drug delivery during the pandemic. As members of the department of pharmacy within NewYork-Presbyterian Hospital, we describe our experiences and processes to overcome challenges faced during the pandemic. Strict inventory management through the use of daily usage reports, frequent communication, and minimization of waste was critical for the management of drug shortages. The creation of guidelines, protocols, and restrictions were not only used to mitigate drug shortages, but also helped educate health care providers and guided medication use. Managing technology through setting up new automatic dispensing cabinets to address hospital expansions and modifying the electronic order entry system to include new protocols and drug shortage information were also vital. Additional key pharmacist functions included provision of investigational drug service support and training of pharmacists, prescribers, nurses, and respiratory therapists to educate and standardize medication use. Through implementation of operational and clinical processes, pharmacists managed critical drug inventory and guided patient treatment. As the pandemic continues, pharmacists will remain vital members of the multidisciplinary team dedicated to the fight against the virus.

Engineering a Brighter Future: The Evolving Role of the Pharmacist in the Era of the HeartMate 3.

Continuous-flow left-ventricular assist devices (CF-LVADs) are an option for patients with end-stage heart failure requiring durable mechanical circulatory support. Two of the older-generation CF-LVADs have been associated with multiple device-related complications, including bleeding and thrombosis. The newest generation CF-LVAD, the HeartMate 3, was engineered specifically to prevent device-related thrombosis. As more data enhance our understanding of the burden of bleeding and thrombotic adverse events, patients with durable mechanical circulatory support may require less-aggressive antithrombotic therapy.

Identification of Cost-Saving Opportunities for the Use of Antithrombin III in Adult and Pediatric Patients.

Thrombate III is a human plasma-derived antithrombin III (AT-III) often utilized in patients on extracorporeal membrane oxygenation (ECMO) with suspected AT-III-mediated heparin resistance. It is supplied as 500-U and 1000-U vials, costing US$4.66 per unit. Literature is limited in describing the clinical value of AT-III in relation to its high cost. The primary objective was to determine conditions of use and associated cost of potentially unnecessary utilization of AT-III at The Johns Hopkins Hospital. Secondary objectives included evaluating the effect of AT-III on anticoagulation parameters and the overall cost utilized and wasted on AT-III. A retrospective cohort study was performed. The primary end point was the total cost associated with potentially unnecessary utilization of AT-III. There were 326 doses of AT-III administered to 65 patients in 2014. There were 177 (54%) potentially unnecessary doses associated with a cost of US$541 634. Antithrombin III repletion significantly increased median AT-III levels in non-ECMO and ECMO patients compared to baseline (non-ECMO: 62% vs 81%, P < .01; ECMO: 63% vs 81%, P < .01); however, 37.3% of ECMO and 49% of non-ECMO patients had therapeutic anticoagulation monitoring parameters prior to administration. A total cost of US$688 478 was spent on administered AT-III and US$417 194 (38%) was wasted. Utilizing restriction criteria and a new dosing strategy potentially results in estimated annual savings of US$556 000. Utilizing restriction criteria and alternative dosing strategies to mitigate waste and unnecessary use has the potential to result in significant cost savings.