Pharmacologic Therapy for Heart Failure With Reduced Ejection Fraction: Closing the Gap Between Clinical Guidelines and Practice

Despite the great progress made in the management of heart failure (HF) with reduced ejection fraction (HFrEF), its prevalence continues to rise owing to an aging population and an epidemic of hypertension, obesity and coronary artery disease. For decades, angiotensin converting enzyme inhibitors and beta blockers have been the mainstay of HFrEF therapy. The recent addition of sacubitril/valsartan and ivabradine to the HF armamentarium has the potential to transform our therapeutic approach to HFrEF, while simultaneously raising some questions and uncertainties on their applicability. In this paper, we review the pathophysiology of HFrEF, discuss already established and novel evidenced-based pharmacologic therapies available for these patients. We also share some therapeutic strategies aimed to optimize HF therapy in specific undertreated patient populations including the elderly and patients with chronic kidney disease, while offering insight on how to tailor therapy in the "real-world." (C) 2017 Elsevier Inc. All rights reserved

Clinician Approach To Subtherapeutic INR Management In Patients With A Heartmate 3 LVAD: A Regional Subgroup Analysis Of The Momentum 3 (CAP And IDE) Trials

Introduction: Patients with Heartmate 3 LVADs are recommended to be on therapeutic anticoagulation consisting of aspirin and warfarin (with a goal INR of 2-3). No specific recommendations exist for the management of subtherapeutic INRs, leading to a variation in management. This study was performed to evaluate clinician behavior in the management of subtherapeutic INRs. Methods: We performed a regional subgroup analysis of the MOMENTUM 3 (CAP and IDE) Trials including 6 centers in the Mid-America Region. All patients implanted with a HeartMate 3 device and discharged alive were included in the analysis. Patients with subtherapeutic INRs (INR \u3c 2) occurring after the index admission underwent manual chart review to determine the management strategies taken by clinicians. Management strategies were separated into three groups: no action taken, isolated adjustment of coumadin, or bridging with IV (heparin, bivalirudin) or parenteral agents (enoxaparin). Results: Among 225 patients included in the analysis, 130 (58%) patients had a total of 235 subtherapeutic INR events. Management strategy was associated with INR (p\u3c0.001; Figure 1). The most common management strategy was a change in coumadin dose (n=100, 42.5%), which occurred at a median (interquartile range [IQR]) INR of 1.70 (1.50-1.80). This was followed by no change in management (n=79, 33.6%), which occurred at a median (IQR) INR of 1.83 (1.60-1.90). Bridging events occurred the least frequently (n=56, 23.8%) at a median (IQR) INR of 1.50 (1.30-1.64). Conclusion: There was a direct relationship between INR and the management strategies of subtherapeutic INRs. At INRs closest to 2, less invasive strategies such as coumadin adjustments or no change were preferred, while bridging strategies (including enoxaparin, heparin, and bivalirudin) were used at lower INRs. The effect of bridging strategies on clinical outcomes including mortality, hospital re-admissions, thromboembolic events, and bleeding are unknown and warrants further evaluation

Anticoagulation Bridging In Patients With Heartmate3 Left Ventricular Assist Device: A Regional Analysis Of The Momentum 3 Trial

Introduction: Advances in left ventricular assist device (LVAD) technologies have led to a significant improvement in pump hemocompatibility. Due to concerns of thromboembolic complications in older generation LVADs, bridging was commonly performed in patients with subtherapeutic INRs. The effects of this strategy on new generation devices are unclear. We analyzed management strategies of subtherapeutic INRs and their effect on outcomes in a subset of patients enrolled in MOMENTUM 3 trial (CAP and IDE). Methods: All patients enrolled in the MOMENTUM 3 trial (CAP and IDE) across 6 centers were screened for inclusion. Patients were included if they underwent implantation of an HMIII device and had a subtherapeutic INR following discharge from their admission for LVAD implant. All episodes of subtherapeutic INR underwent manual chart review to evaluate management strategies taken by clinicians. Strategies were divided into two groups, bridging (with parenteral or intravenous agents) or non-bridging (consisting of adjustments or no change in coumadin dosing). The primary outcome was a composite of death, rehospitalization, CVA, and bleeding events. Results: Of the 225 patients included in the analysis there were total of 235 subtherapeutic INR events. Fifty-six (23.8%) of these INR\u27s were treated with bridging (n= 30 with parenteral agents, n=26 with IV agents) and 179 patients that were not bridged (n=100 coumadin dose adjustment, n=79 no change in coumadin dose). There was no difference in the composite outcome of patients that were bridged compared to those that were not. Conclusion: Subtherapeutic INR is a common event in patients with HM3 LVAD. The management strategy of subtherapeutic INR varies. Management strategy had no effect on mortality, rehospitalization, CVA, or bleeding events

Anticoagulation bridging in patients with left ventricular assist device: A regional analysis of HeartMate 3 recipients

Advances in left ventricular assist device technologies have led to an improvement in pump hemocompatibility and outcomes. Because of concerns of thromboembolic complications in prior generations of left ventricular assist devices, bridging with parenteral anticoagulants was routinely. Management strategies of subtherapeutic INRs and their effects on the current generation of devices deserve review. We performed analysis of the MOMENTUM 3 trial including 6 centers in the mid-America region. Patients with subtherapeutic INRs (INR \u3c 2) occurring after the index admission underwent chart review to determine the management strategies taken by clinicians. Strategies were divided into two groups, bridging or nonbridging. Of the 225 patients included in the analysis, 130 (58%) patients had a total of 235 subtherapeutic international normalized ratio (INR) events. Most (n = 179, 76.2%) of these INRs were not bridged (n = 100 warfarin dose adjustment, n = 79 no change in warfarin dose). Among those INRs (n = 56, 23.8%) treated with bridging, approximately half (n = 30, 53.6%) were treated with subcutaneous agents and other half (n = 26, 46.4%) were treated with intravenous agents. There was no difference in individual outcomes or composite endpoints of death, rehospitalization, CVA, or bleeding events between the groups