Assessment of Temporary Warfarin Reversal in Patients With Left Ventricular Assist Devices: the KVAD Study.

BACKGROUND: Patients with left ventricular assist devices (LVADs) require interruption of warfarin for invasive procedures, but parenteral bridging is associated with many complications. Four-factor prothrombin complex concentrate (4F-PCC) can temporarily restore hemostasis in patients undergoing anticoagulation with warfarin. OBJECTIVES: This pilot study evaluated the strategy of using variable-dose 4F-PCC to immediately and temporarily reverse warfarin before invasive procedures without holding warfarin in patients with LVADs. The duration of effect of 4F-PCC on factor levels and time to reestablish therapeutic anticoagulation post procedure were assessed. METHODS: Adult patients with LVADs and planned invasive procedures were enrolled from a single center. Warfarin was continued uninterrupted. The 4F-PCC dose administered immediately pre-procedure was based on study protocol. International normalized ratio (INR)- and vitamin K-dependent factor levels were collected before and during the 48 hours after 4F-PCC administration. The use of parenteral bridging, International Society for Thrombosis and Haemostasis major and clinically relevant nonmajor bleeding (CRNMB) and thromboembolic events at 7 and 30 days were collected. RESULTS: In 21 episodes of 4F-PCC reversal, median baseline INR was 2.7 (IQR 2.2-3.2). The median dosage of 4F-PCC administered was 1794 units (IQR 1536-2130). At 24 and 48 hours post 4F-PCC administration, median INRs were 1.8 (IQR 1.7-2.0) and 2.0 (IQR 1.9-2.4). Two patients required postoperative bridging. One patient experienced major bleeding within 72 hours, and 2 experienced CRNMB within 30 days. There were no thromboembolic events. Baseline and post 4F-PCC vitamin K-dependent factor levels corresponded with changes in INR values. The median time to achieve therapeutic INR post-procedure was 2.5 days (IQR, 1-4). CONCLUSION: Administration of 4F-PCC for temporary reversal of warfarin for invasive procedures in patients with LVADs allowed for continued warfarin dosing with minimal use of post-intervention bridging, limited bleeding and no thromboembolic events.

Virtual Care Team Guided Management of Patients With Heart Failure During Hospitalization.

BACKGROUND: Scalable and safe approaches for heart failure guideline-directed medical therapy (GDMT) optimization are needed. OBJECTIVES: The authors assessed the safety and effectiveness of a virtual care team guided strategy on GDMT optimization in hospitalized patients with heart failure with reduced ejection fraction (HFrEF). METHODS: In a multicenter implementation trial, we allocated 252 hospital encounters in patients with left ventricular ejection fraction ≤40% to a virtual care team guided strategy (107 encounters among 83 patients) or usual care (145 encounters among 115 patients) across 3 centers in an integrated health system. In the virtual care team group, clinicians received up to 1 daily GDMT optimization suggestion from a physician-pharmacist team. The primary effectiveness outcome was in-hospital change in GDMT optimization score (+2 initiations, +1 dose up-titrations, -1 dose down-titrations, -2 discontinuations summed across classes). In-hospital safety outcomes were adjudicated by an independent clinical events committee. RESULTS: Among 252 encounters, the mean age was 69 ± 14 years, 85 (34%) were women, 35 (14%) were Black, and 43 (17%) were Hispanic. The virtual care team strategy significantly improved GDMT optimization scores vs usual care (adjusted difference: +1.2; 95% CI: 0.7-1.8; P < 0.001). New initiations (44% vs 23%; absolute difference: +21%; P = 0.001) and net intensifications (44% vs 24%; absolute difference: +20%; P = 0.002) during hospitalization were higher in the virtual care team group, translating to a number needed to intervene of 5 encounters. Overall, 23 (21%) in the virtual care team group and 40 (28%) in usual care experienced 1 or more adverse events (P = 0.30). Acute kidney injury, bradycardia, hypotension, hyperkalemia, and hospital length of stay were similar between groups. CONCLUSIONS: Among patients hospitalized with HFrEF, a virtual care team guided strategy for GDMT optimization was safe and improved GDMT across multiple hospitals in an integrated health system. Virtual teams represent a centralized and scalable approach to optimize GDMT.

Evaluation of the use of direct oral anticoagulants for the management of heparin-induced thrombocytopenia.

Historically, treatment of heparin-induced thrombocytopenia (HIT) includes a non-heparin parenteral anticoagulant with bridging to warfarin once platelets recover. Data supporting the use of direct oral anticoagulants (DOACs) for HIT treatment are limited. Given the paucity of evidence for the use of DOACs in HIT, the aim of this study is to describe the prescribing patterns of DOACs for HIT at our institution. This is a single center, retrospective chart evaluation of patients admitted from January 2017 to October 2020 with a confirmed diagnosis of HIT. Twenty-six patients were identified; 21 patients (81%) received initial parenteral treatment and 5 patients (19.2%) with initial DOAC treatment. The most frequently used DOAC was apixaban at the VTE treatment dose [15 (57.7%)] followed by the reduced dose of apixaban [5 (19.2%)]. Of the patients initially treated with a parenteral agent, 11 (42.3%) were transitioned to a DOAC after platelet recovery, 7 (26.9%) transitioned as platelets were steadily increasing, and 3 (11.5%) transitioned at the time of discharge (prior to platelet recovery). Platelet recovery was achieved in 23 patients (88.5%) at a median of 5 days (IQR 2.8-8.3) after HIT diagnosis. No new thrombotic or bleeding events occurred within 30 days of HIT diagnosis. In our patients treated with a DOAC for HIT, no progression of HIT was observed. Apixaban was the most frequently utilized DOAC. Most patients received a parenteral anticoagulant prior to DOAC initiation. All patients managed with a DOAC as initial treatment achieved platelet recovery within 30 days of HIT diagnosis.

Evaluation of safety of switching between oral P2Y12 inhibitors: a descriptive study.

PURPOSE: Dual antiplatelet therapy with aspirin and a P2Y12 inhibitor is recommended for patients with acute coronary syndrome and after percutaneous coronary intervention with stenting in stable coronary artery disease to help prevent further thromboembolic events. However, there is limited guidance on appropriate strategies for switching between oral P2Y12 inhibitors. The aim of this study was to evaluate safety of switching modalities at our institution and compare them to the recently published expert consensus recommendations. METHODS: This was a retrospective, descriptive analysis of patients admitted to Brigham and Women's Hospital from January 2015 to December 2018. Patients were included if they were at least 18 years of age and had documented administrations of two or more oral P2Y12 inhibitors during the same admission. The major safety endpoint was incidence of major adverse cardiac events (MACE) (cardiovascular death, myocardial infarction, stroke, and non-coronary artery bypass grafting (CABG)-related bleeding) at seven days or until hospital discharge. Minor endpoints included the incidence of in-stent thrombosis, number of patients who received appropriate loading doses (LD) before and after the recently published recommendations, and documented reason for switching between agents. RESULTS: There were 253 patients included in the final analysis. Of these, 83 patients were on clopidogrel as the first agent prior to switching, 9 patients were on prasugrel, and 161 were on ticagrelor. There was no incidence of the primary safety endpoint observed in any group. However, the number of patients who received a LD when switching between oral P2Y12 inhibitors increased from 80.0% to 87.0% after publication of the expert consensus paper. The most common reasons for switching from one agent to another were cost/insurance coverage (19.0%), need for triple therapy (16.0%), and bleeding risk (11.0%). CONCLUSION: Different switching modalities were not associated with an increase in MACE at our institution; however, larger randomized controlled trials are warranted.

Virtual optimization of guideline-directed medical therapy in hospitalized patients with heart failure with reduced ejection fraction: the IMPLEMENT-HF pilot study.

AIMS: Implementation of guideline-directed medical therapy (GDMT) for heart failure with reduced ejection fraction (HFrEF) remains incomplete. Non-cardiovascular hospitalization may present opportunities for GDMT optimization. We assessed the efficacy and durability of a virtual, multidisciplinary 'GDMT Team' on medical therapy prescription for HFrEF. METHODS AND RESULTS: Consecutive hospitalizations in patients with HFrEF (ejection fraction ≤40%) were prospectively identified from 3 February to 1 March 2020 (usual care group) and 2 March to 28 August 2020 (intervention group). Patients with critical illness, de novo heart failure, and systolic blood pressure <90 mmHg in the preceeding 24 hs prior to enrollment were excluded. In the intervention group, a pharmacist-physician GDMT Team provided optimization suggestions to treating teams based on an evidence-based algorithm. The primary outcome was a GDMT optimization score, the sum of positive (+1 for new initiations or up-titrations) and negative therapeutic changes (-1 for discontinuations or down-titrations) at hospital discharge. Serious in-hospital safety events were assessed. Among 278 consecutive encounters with HFrEF, 118 met eligibility criteria; 29 (25%) received usual care and 89 (75%) received the GDMT Team intervention. Among usual care encounters, there were no changes in GDMT prescription during hospitalization. In the intervention group, ß-blocker (72% to 88%; P = 0.01), angiotensin receptor-neprilysin inhibitor (6% to 17%; P = 0.03), mineralocorticoid receptor antagonist (16% to 29%; P = 0.05), and triple therapy (9% to 26%; P < 0.01) prescriptions increased during hospitalization. After adjustment for clinically relevant covariates, the GDMT Team was associated with an increase in GDMT optimization score (+0.58; 95% confidence interval +0.09 to +1.07; P = 0.02). There were no serious in-hospital adverse events. CONCLUSIONS: Non-cardiovascular hospitalizations are a potentially safe and effective setting for GDMT optimization. A virtual GDMT Team was associated with improved heart failure therapeutic optimization. This implementation strategy warrants testing in a prospective randomized controlled trial.

Evaluation of Direct Oral Anticoagulant Prescribing in Patients With Moderate to Severe Renal Impairment.

Patients with renal impairment require dose adjustments for direct oral anticoagulants (DOACs), though there is uncertainty regarding their use in severe chronic kidney disease. Inappropriately dosed DOACs may increase risk of ischemic events when under-dosed, or risk of bleeding when over-dosed. The purpose of this study was to describe DOAC selection, dosing strategies, and associated clinical outcomes in patients with moderate to severe renal impairment at our institution. This was a single-center retrospective analysis of adult outpatients with moderate to severe renal impairment (estimated creatinine clearance <50 mL/min, including need for hemodialysis) who were prescribed a DOAC by a cardiologist between June 1, 2015 and December 1, 2018. Outcomes evaluated included the percentage of patients who received appropriate and inappropriate DOAC dosing, prescriber reasons for inappropriate DOAC dosing if documented, and incidence of thrombotic and bleeding events. A total of 207 patients were included. Overall, 61 (29.5%) patients received inappropriate dosing, with 43 (70.5%) being under-dosed and 18 (29.5%) being over-dosed as compared to FDA-labeled dosing recommendations for atrial fibrillation or venous thromboembolism (VTE). By a median follow-up duration of 20 months, stroke occurred in 6 (3.3%) patients receiving DOACs for atrial fibrillation, and VTE occurred in 1 (4.3%) patient receiving a DOAC for VTE. International Society on Thrombosis and Haemostasis major or clinically relevant nonmajor bleeding occurred in 25 (12.1%) patients. Direct oral anticoagulants were frequently prescribed at off-label doses in patients with moderate to severe renal impairment, with a tendency toward under-dosing.