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.

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.

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.