Faculty Bibliography

Cardiac arrest has many implications for morbidity and mortality. Few interventions have been shown to improve return of spontaneous circulation (ROSC) and long-term outcomes after cardiac arrest. Ischemic-reperfusion injury upon achieving ROSC creates an imbalance between oxygen supply and demand. Multiple events occur in the postcardiac arrest period, including excitotoxicity, mitochondrial dysfunction, and oxidative stress and inflammation, all of which contribute to ongoing brain injury and cellular death. Given that complex pathophysiology underlies global brain hypoxic ischemia, neuroprotective strategies targeting multiple stages of the neuropathologic cascade should be considered as a means of mitigating secondary neuronal injury and improving neurologic outcomes and survival in cardiac arrest victims. In this review article, we discuss a number of different pharmacologic agents that may have a potential role in targeting these injurious pathways following cardiac arrest. Pharmacologic therapies most relevant for discussion currently include memantine, perampanel, magnesium, propofol, thiamine, methylene blue, vitamin C, vitamin E, coenzyme Q₁₀ , minocycline, steroids, and aspirin.

Prescribing patterns for oral anticoagulants in patients with nonvalvular atrial fibrillation and venous thromboembolism is shifting from vitamin K antagonists, such as warfarin to the direct oral anticoagulants (DOACs), such as dabigatran, rivaroxaban, and apixaban. Although many hospital systems have implemented clinical decision support or enhanced monitoring for patients prescribed warfarin, there is limited evidence to suggest similar levels of enhanced monitoring for DOACs. The antithrombotic stewardship team at our institution developed guidelines and implemented computerized clinical decision support (CCDS) tools to enhance medication and patient safety related to the DOACs. We sought to assess the safety and effectiveness of these CCDS tools available to clinicians upon DOAC prescription in hospitalized patients. We performed a retrospective review of 121 patients who received at least two doses of a DOAC from January 2013 to July 2014. We assessed dosing of the DOAC according to the CCDS provided upon order entry. Adherence to CCDS was 80% (n = 24), 75% (n = 46), and 87% (n = 27) in the dabigatran, apixaban, and rivaroxaban group, respectively. Our data demonstrate that implementing CCDS for DOACs into the electronic medical record may ensure safe prescribing of high-risk medications.

Objective/UNASSIGNED:Drug interactions are a common cause of morbidity and mortality and may require prompt discontinuation of therapeutic regimens due to harmful side effects. Patients with acute coronary syndromes are likely to be prescribed multiple medications that are metabolized through the cytochrome P450 system, increasing the probability for drug interaction. Atorvastatin and simvastatin are both well known to interact with the oral P2Y12 agent ticagrelor. The purpose of this paper is to describe the interaction of ticagrelor with rosuvastatin leading to rhabdomyolysis, which is less clearly defined in the literature. Method/UNASSIGNED:We report a case of a 74-year-old male who presented with bilateral lower extremity weakness and difficulty ambulating for one month after being prescribed ticagrelor for a drug eluting stent, in the setting of already being on rosuvastatin. His clinical picture and laboratory findings were consistent with a diagnosis of rhabdomyolysis. His medications were adjusted to a regimen of clopidogrel and alirocumab. One month later, he returned to his baseline status. Results/UNASSIGNED:The mechanism of interaction between rosuvastatin and ticagrelor appears to be multifactorial. It may be caused by CYP450-mediated metabolism from a small amount of crossover between isoenzymes. Ticagrelor may also cause acute kidney injury, increasing the concentration of rosuvastatin. Other mechanisms of interaction include genetic differences in the organic anion transporter polypeptides and transportation through p-glycoprotein. Conclusion/UNASSIGNED:Future pharmacokinetic studies are warranted to better understand the interaction.

Background : The activated partial thromboplastin time (aPTT) and anti-factor Xa (anti-Xa) test are often used as surrogate markers of heparin's effects, though anti-Xa may be preferred due to less variability and closer relation to heparin's activity in the body. The antithrombotic and hemostatic therapy oversight group at NYU Langone Health (NYULH) implemented a nurse-titrated protocol, utilizing anti-Xa to titrate and monitor time in therapeutic range with heparin. Aims : To evaluate adherence to the nurse-driven continuous infusion unfractionated heparin protocol and assess time to therapeutic anti-Xa, median time in therapeutic range, and clinical outcomes including bleeding and thrombotic events. Methods : This was a retrospective chart review. Adult patients (>18 years old) who received heparin based on nurse-driven titration protocol between March 2019 and June 2019 at NYULH were included. Patients that received heparin for less than 24 hours, had an interruption in heparin for more than 12 hours, or received a direct oral anticoagulant (DOAC) prior to heparin initiation were excluded. Data collection included baseline characteristics, relevant concomitant medications, heparin administration including bolus dose, infusion rate, length of therapy, time within therapeutic range, bleeding events, and thrombotic events. The primary outcome was adherence to the protocol. Secondary outcomes included time within therapeutic range, thrombotic or bleeding events. Results : Adherence to the protocol, defined as deviation of not more than 25% of protocol elements, including but not limited to adequate bolus dose, correct body weight used, time to first anti-Xa, and correct adjustment (units/kg) in heparin dose based on anti-Xa was observed 85% of the time, with the majority of dose titrations occurring by nursing, per protocol in 82% of patients. Therapeutic anti-Xa levels were achieved at a median of 30 hours into IV UFH therapy. Conclusions : It remains a challenge to achieve a stable goal anti-Xa level within 24 hours of heparin initiation

OBJECTIVES/OBJECTIVE:infection (CDI) while receiving systemic antibiotics to prevent CDI recurrence. However, this practice has not been studied in pediatric patients. The objective of this study was to assess the utility of secondary OVP in pediatric patients with previous CDI who received subsequent antibiotic exposure. METHODS:A multicampus, retrospective cohort evaluation was conducted among patients aged ≤18 years with any history of clinical CDI and receiving systemic antibiotics in a subsequent encounter from 2013-2019. Patients who received concomitant OVP with antibiotics were compared with unexposed patients. The primary outcome was CDI recurrence within 8 weeks after antibiotic exposure. Infection with vancomycin-resistant enterococci and risk factors for CDI recurrence were assessed. RESULTS:= .04). CONCLUSIONS:Secondary OVP while receiving systemic antibiotics reduces the risk of recurrent CDI in pediatric patients with a history of CDI.

Human immunodeficiency virus (HIV) is associated with increased rates of cardiovascular disease and vascular events, and people living with HIV (PLWH) may often have indications for therapeutic anticoagulation. However, the ideal anticoagulant in PLWH remains unknown. This retrospective cohort evaluated the tolerability and effectiveness of oral anticoagulants in PLWH. The primary outcome was tolerability, defined as a composite of bleeding and/or discontinuation rates. The secondary outcomes included recurrent thromboembolism, bleeding, and discontinuations, independently. There were 92 patients included for analysis, 48 in the direct oral anticoagulant (DOAC) arm and 44 in the warfarin arm. There were 35 (38%) PLWH that did not tolerate oral anticoagulation therapy in the total cohort. Among these, 19 received a DOAC and 16 received warfarin. There were 16 (17%) PLWH that experienced a bleeding event: six in the DOAC arm and 10 in the warfarin arm. There were 15 (16%) PLWH that experienced recurrent thromboembolism, with similar rates between DOAC versus warfarin (10, 21% vs 5, 11%, respectively; p = 0.11). The most commonly prescribed HIV regimens were protease inhibitor and integrase inhibitor-based regimens. Overall, anticoagulation-related outcomes with either a DOAC or warfarin were poor in our cohort of PLWH, with high rates of bleeding, discontinuations, and recurrent thromboembolism. Further studies are necessary to validate and assess reasons for poor tolerability.

ABSTRACT/UNASSIGNED:Intracardiac thrombus (ICT) formation is a common complication of several cardiovascular diseases. Warfarin is recommended for treatment of ICT by guidelines based on observational studies occurring prior to the advent of non-vitamin K antagonist direct oral anticoagulants (DOACs). We aim to evaluate the current prescribing patterns at our institution and to compare the efficacy and safety profiles of warfarin versus DOACs for ICT.This is a retrospective review of adult patients treated with oral anticoagulation for ICT between May 2013 and December 2019. Our primary endpoint was complete thrombus resolution. Secondary outcomes included time to resolution of thrombus, treatment failure, and duration of therapy. Safety endpoints included stroke and systemic embolism (SSE) and bleeding events.A total of 123 patients were included (DOAC n=61; warfarin n=62). At baseline, more patients in the DOAC group had anemia (6 [10%] vs 0 [0%], p=0.013) and alcohol use disorder (6 [10%] vs 0 [0%], p = 0.013). Complete thrombus resolution occurred in 50 (82%) and 46 (74%) patients in the DOAC and warfarin groups, respectively (p = 0.298). There was a shorter time to thrombus resolution in the DOAC group versus the warfarin group (63 days [IQR 40, 138] vs 123 days [IQR 86, 244], p = 0.003). There were no differences found in SSE or bleeding between the groups (DOAC 11 [19%] vs warfarin 17 [28%], p = 0.213). For patients with an ICT, treatment with a DOAC for at least 3 months may be a comparable alternative to warfarin in terms of safety and efficacy.

BACKGROUND/UNASSIGNED:There is a lack of robust data evaluating outcomes of enoxaparin "bridge" therapy in left ventricular assist device (LVAD) patients. METHODS/UNASSIGNED:We performed a retrospective study of HeartMate II (HM II) and HeartWare HVAD recipients that received therapeutic enoxaparin as "bridge" therapy to describe bleeding and thrombotic events and compare outcomes between devices. The primary endpoint was the incidence of bleeding within 30 days of "bridge" episode. Major bleeding was defined by INTERMACS criteria. RESULTS/UNASSIGNED:= .02). We observed 3 (1%) thromboembolic events in 2 (4%) patients with an HVAD device. On multivariate analysis, the presence of a HM II device was associated with a 4-fold increased risk of bleeding. CONCLUSION/UNASSIGNED:We found the use of enoxaparin "bridge" therapy to be associated with a higher incidence of bleeding in patients with a HM II device compared with an HVAD device. Assessment of device- and patient-specific factors should be evaluated to minimize bleeding events.