Faculty Bibliography

Antithrombotic therapy for stroke prevention in patients with atrial fibrillation (AF) has dramatically shifted from warfarin, a vitamin K antagonist, to the direct oral anticoagulants (DOACs) such as dabigatran, apixaban, and rivaroxaban. In patients with contraindications to oral anticoagulation, left atrial appendage occlusion (LAAO) devices, such as the Watchmanâ„¢ device, may be considered; however, temporary postimplantation antithrombotic therapy is still a recommended practice. We present a case of complex antithrombotic management, post LAAO device implantation, designed to avoid drug interactions with concomitant rifampin use and remained necessary secondary to subsequent device leak. This case highlights the challenges of antithrombotic therapy post LAAO device placement in a complex, but representative, patient.

Although Candida species are common pathogens for nosocomial infections, Candida endocarditis is still considered a rare entity. Here, we report two cases of Candida parapsilosis endovascular infections in patients with prosthetic valves, both of which responded to combination antifungal therapy without surgical intervention. Additionally, T2 magnetic resonance (T2MR) was used to assess for resolution of invasive candidiasis. The first case is of an elderly man with Candida parapsilosis endovascular infection who responded to combination antifungal therapy with micafungin and fluconazole followed by suppressive therapy, without surgical intervention. The second case is of a middle-aged man with Candida parapsilosis prosthetic valve endocarditis who also responded to combination antifungal therapy with micafungin, flucytosine and fluconazole, without surgical intervention.

Objective Patients with acute myelogenous leukemia or myelodysplastic syndrome undergoing induction chemotherapy are at increased risk of invasive fungal infection due to prolonged, severe neutropenia. Due to this risk, national guidelines recommend invasive fungal infection prophylaxis in this population until the resolution of neutropenia. Although posaconazole has demonstrated superiority over fluconazole and itraconazole, there is limited evidence for voriconazole for invasive fungal infection prophylaxis in this population. Even less data are available comparing posaconazole and voriconazole directly. The study objective was to investigate the efficacy and safety of delayed-release posaconazole tablets versus voriconazole for primary invasive fungal infection prophylaxis. The primary outcome was rate of discontinuation of either agent. Secondary outcomes included specific rates of discontinuation due to adverse events and drug-drug interactions, rates of breakthrough invasive fungal infection, and 30-day and 100-day mortality rates. Methods This was a retrospective cohort study of adult patients admitted to NYU Langone Health between 1 January 2014 and 31 August 2017 and initiated on invasive fungal infection prophylaxis during induction or reinduction chemotherapy for acute myelogenous leukemia or myelodysplastic syndrome. Results In total, 77 patients were included in the study: 43 using posaconazole delayed-release tablets and 34 using oral voriconazole. In the posaconazole group, 30% of patients (n = 13) discontinued therapy for any reason compared with 35% (n = 12) of patients in the voriconazole group (p = 0.64). A higher percentage of patients in the voriconazole group discontinued due to adverse events (6 patients, 18% vs. 1 patient, 2%, p = 0.04). Mortality rates at 30 and 100 days were similar between both groups. No breakthrough invasive fungal infections was noted in either group. Conclusion Overall, discontinuations for any reason were similar in patients taking both posaconazole delayed-release and oral voriconazole. Both posaconazole delayed-release tablets and oral voriconazole appear to be effective at preventing invasive fungal infection in acute myelogenous leukemia and myelodysplastic syndrome patients undergoing induction chemotherapy, although posaconazole may be more tolerable.

Carfilzomib is a second-generation proteasome inhibitor that irreversibly inhibits chymotrypsin-like (CT-L) activities of the proteasome, and is indicated for relapsed or refractory multiple myeloma. Cardiotoxicity is a well-established adverse effect of carfilzomib. The extent of cardiac toxicity in the literature spans anywhere from palpitations to cardiac arrest, with the most commonly reported manifestation being new-onset or worsening heart failure. A pre-clinical study of the pharmacokinetics and pharmacodynamics of carfilzomib given via intravenous bolus or 30-minute infusion in rats showed that carfilzomib can strongly induce apoptosis and potently damage cardiac myocytes at clinically relevant concentrations. Moreover, the mortality rate with the bolus administration was 44% whereas the same dose administered as a 30-minute infusion did not result in mortality. There remains limited clinical data regarding the safety of carfilzomib at doses of 27-56 mg/m2 based on infusion times as these doses have not been well studied. This retrospective review was conducted to evaluate the safety of carfilzomib at doses >27 mg/m2 at all infusion times.

The use of enoxaparin in specialty populations-including those with renal dysfunction, extremeness of body weight, pregnant patients, and pediatric patients-has not been studied in clinical trials. Monitoring anti-factor Xa activity (antiXa) as a surrogate to measure the activity of enoxaparin may be of interest. A case series of patients admitted to New York University Langone Health between December 2012 and July 2014 who received at least three consecutive doses of enoxaparin for the treatment of VTE and had a peak antiXa level drawn at steady state were evaluated. Patients were included if they were ≤ 18 years of age or if they were > 18 years of age and met one of the following criteria: pregnant, creatinine clearance (CrCl) ≤ 50 ml/min at the time of initiation of enoxaparin, or had a body weight ≤ 50 kg or ≥ 120 kg. A total of 31 patients were included in the analysis. The percentage of patients who achieved a therapeutic antiXa level (0.5-1.2 IU/mL for twice daily enoxaparin or 1-2 IU/mL for once daily enoxaparin) at the time of the first antiXa level drawn was greatest for the adult patients; however, the patients with renal impairment and low body weight were more likely to be sub-therapeutic at first antiXa level check. In addition, neonates and young children required increased enoxaparin doses to achieve therapeutic antiXa. Optimal dosing of enoxaparin in specialty populations has not been established. Furthermore, higher initial doses of enoxaparin may be needed in pediatric patients to attain therapeutic antiXa levels.

Background: Novoseven is a recombinant preparation of human factor VIIa (rFVIIa) indicated for the treatment of bleeding episodes and perioperative management. Aims: To evaluate the cost and utilization of rFVIIa at a large academic medical center. Methods: We performed a retrospective review. Data collection included baseline characteristics, past medical history, and antithrombotic use. Utilization of rVIIa included indication for use, number of doses, and blood product administration within 24 hours. Incidence of venous thromboembolism (VTE), stroke, transient ischemic attack (TIA), death from systemic embolism, myocardial infarction (MI), hypersensitivity, and disseminated intravascular coagulation (DIC) were also collected. The primary outcome was utilization and cost of rVIIa at NYULH. Secondary outcomes included compliance to NYULH off-label dosing guideline, blood product administration, adverse effects, and thromboembolic events. Results: The majority of rFVIIa use was for refractory bleeding after cardiac surgery. Dosing was according to NYULH guideline, lower, and higher than recommended in 76.5%, 3.9% and 17.6% of cases respectively. The costs of rVIIa decreased after development of the off-label dosing guideline and transition from blood bank to pharmacy. The total incidence of thromboembolic events within 30 days was 19.6%; 17.6% arterial and 2% venous. Seventy percent of patients with an adverse event were over 70 years of age. Use of rFVIIa reduced the median number of units of blood products administered. Conclusions: Administration of rFVIIa for cardiac surgery appears to be effective for hemostasis. Transitioning rFVIIa from the blood bank to pharmacy and implementation of a dosing guideline appears to have reduced costs. Patients receiving rFVIIa should be monitored for thromboembolic events. Elderly patients may be at higher risk for thromboembolic events and further literature is needed to determine the optimal use of rFVIIa or if other hemostatic agents may be warranted in this population