Cardiotoxic effects of chemotherapy: A review of both cytotoxic and molecular targeted oncology therapies and their effect on the cardiovascular system.

Cardiotoxic effects of chemotherapy and targeted drugs are ubiquitous and challenging in the field of oncology therapeutics. The broad spectrum of toxicities ranging from ischemic, hypertensive, cardiomyopathic, and arrhythmic complications can present as a significant challenge for clinicians treating cancer patients. If early diagnosis and intervention of cardiotoxic complications is missed, this can lead to delay or abrogation of planned treatment, which can potentially culminate to significant morbidity due to not only the cardiotoxic complications but also the progression of cancer. Hence, full knowledge of cardiovascular complications of chemotherapeutic agents, essential diagnostics tests to order, and appropriate management is paramount to oncologist, oncology pharmacists, and scientific clinical investigators. The aforementioned is particularly true in the current oncology era of plenteous early clinical trials studying several pathway/molecular-targeting agents with an increased cardiotoxic potential and the rapid expedited approval of those drugs by the FDA. Herein, we present a review discussing cardiotoxic effects of drugs and guidelines for management of the toxicities to assist the medical field in general managing patients with cancer.

Practice Patterns of Venous Thromboembolism Prophylaxis in Underweight, Critically Ill Patients with Neurologic Injury.

PURPOSE: Venous thromboembolism (VTE) prophylaxis in underweight patients with neurologic injury remains unaddressed by guidelines and primary literature. This study aimed to describe VTE prophylaxis strategies employed in this population and compare the impact of underweight and non-obese patients on thrombotic and bleeding events. METHODS: A retrospective review of adults admitted with a diagnosis of neurologic injury to a neurology/neurosurgery intensive care unit (ICU) over 6 years. Patients admitted ≥72 h with an order for VTE prophylaxis during admission, and a body mass index (BMI) <30 kg/m2 were included. Patients were stratified to underweight (BMI ≤18.5 kg/m2 or weight ≤50.0 kg) or non-obese (BMI 18.6-29.9 kg/m2) groups and matched, 2:1, on age, diagnosis, and disease severity. RESULTS: The most common regimen in the underweight (n = 107) and non-obese (n = 214) group was unfractionated heparin (UFH) 5000 units subcutaneously Q12 h (69.1 vs. 83.6%; p = 0.003). Only underweight patients received UFH 2500 units subcutaneously Q12 h (17.8 vs. 0.0%; p < 0.0001). The proportion of overall bleeding and thrombotic events while receiving VTE prophylaxis was not significantly different. The proportion of underweight patients developing intracranial hematoma expansion while receiving prophylaxis versus non-obese patients (45.5 vs. 8.3%; p = 0.017) was significant. Patients receiving >150 units/kg/day of UFH displayed a trend toward increased risk of bleeding (9.7 vs. 4.2%; p = 0.064). CONCLUSIONS: Current practice does not reflect dose reductions for neurologically injured, underweight patients. Caution should be considered when using increased doses of UFH in neurologically injured patients that are underweight and/or may be exposed to >150 units/kg/day of UFH. Continued assessment of VTE prophylaxis is needed to confirm these findings.

Clinical Experience With Pharmacological Venous Thromboembolism Prophylaxis in the Underweight and Critically Ill.

BACKGROUND: The optimal regimen for pharmacological prophylaxis of venous thromboembolism (VTE) in underweight, critically ill patients is unknown. OBJECTIVE: To describe prescribing patterns for VTE prophylaxis in underweight (≤50 kg or body mass index ≤18.5 kg/m(2)), critically ill patients and identify the prevalence of VTE and bleeding. METHODS: This was a retrospective cohort study that included patients who received standard- or reduced-dose VTE prophylaxis for ≥48 hours. RESULTS: A total of 295 individuals were included in the study. The majority of underweight patients in this study (79.7%) received unfractionated heparin, 5000 units 3 times daily. No statistically significant difference in the prevalence of clinically relevant VTEs between the reduced- and standard-dose groups was observed (4.4% vs 5.6%, P = 1.00), but a higher proportion of bleeding events was identified within the standard-dose group (6.7% vs 11.2%, P = 0.4). CONCLUSIONS: Empirical dose reductions of VTE prophylaxis are infrequently used in underweight, critically ill patients. Further studies need to be conducted that assess the safety and efficacy of reduced-dose VTE prophylactic regimens in this population to determine if acceptable efficacy can be achieved, with lower risks of bleeding.

Use of a Shared Canister Protocol for the Delivery of Metered-Dose Inhalers in Mechanically Ventilated Subjects.

BACKGROUND: Mechanically ventilated patients often need bronchodilators administered via a metered-dose inhaler (MDI). Unfortunately, there are no data examining the impact of shared canister delivery of MDI therapy in mechanically ventilated patients. METHODS: A prospective trial was conducted with subjects assigned to shared canister MDI therapy or single-patient canister MDI therapy. Outcomes assessed were occurrence of ventilator-associated pneumonia (VAP), hospital mortality, length of stay, ventilator-associated events, and MDI costs. RESULTS: Among 486 screened patients, 353 were included for analysis of which 201 (56.9%) received shared canister MDI therapy and 152 (43.1%) received single-patient canister therapy. VAP (7.0% vs 4.6%, P = .35), hospital mortality (21.9% vs 20.4%, P = .73), and ventilator days (median [interquartile range] 3.1 [0.9-7.5] d vs 2.7 [1.2-7.1] d, P = .62) were similar between the shared canister and single-patient canister groups. We did not observe clinically important differences for ventilator-associated events between study groups in our logistic regression analysis (P = .07). There was a savings of $217/subject in the shared canister group due to the use of 299 fewer MDIs. CONCLUSIONS: Our study found that shared canister MDI therapy compared with single-patient MDI use was associated with a significant cost savings and similar rates of VAP, hospital mortality, and length of stay but a greater prevalence of ventilator-associated events. This finding suggests that shared canister delivery of MDIs may be a cost-effective practice in mechanically ventilated patients. Based on our findings, further studies examining the overall safety of shared canister use in mechanically ventilated patients seem warranted before recommending their routine use. (ClinicalTrials.gov registration NCT01935388.).

Identifying critically ill patients at risk for inappropriate antibiotic therapy: a pilot study of a point-of-care decision support alert.

OBJECTIVE: To develop an automated alert aimed at reducing inappropriate antibiotic therapy of serious healthcare-associated infections. DESIGN: Single-center cohort study from November 2011 to November 2012. SETTING: Barnes-Jewish Hospital (1,250-bed academic hospital). PATIENTS: A total of 3,616 critically ill patients receiving treatment with antibiotics targeting healthcare-associated infections due to Gram-negative bacteria. INTERVENTIONS: Upon antibiotic order entry in the ICU for a Gram-negative antibiotic, the antibiotic and microbiologic history for each patient was electronically queried in real time across all 13 BJC HealthCare hospitals. Patients were assigned to the alert group if they had exposure to the same antibiotic class currently being prescribed (cefepime, meropenem, or piperacillin-tazobactam) or had a positive culture isolating a Gram-negative organism with resistance to the prescribed antibiotic in the previous 6 months. MEASUREMENTS AND MAIN RESULTS: Nine hundred patients (24.2%) generated an alert. Alerted patients were significantly more likely to receive inappropriate antibiotic therapy (7.1% vs. 2.9%; p < 0.001). Based on clinical information available in the alert, 34 of 64 of the alerted patients that received inappropriate therapy (53.1%) could have received an alternative ß-lactam antibiotic with in vitro susceptibility to the identified pathogen. Independent predictors (adjusted odds ratio [95% CI]) of inappropriate therapy included alert generation (1.788 [1.167-2.740]; p = 0.008), medical ICU patients (1.528 [1.007-2.319]; p = 0.046), and a pulmonary source of infection (2.063 [1.363-3.122]; p = 0.0001). Patients in the alert group had significantly greater hospital mortality (29.9% vs. 23.6%; p < 0.001) and hospital length of stay (median, 13.1 vs. 10.7 d; p < 0.001) compared with nonalert patients. CONCLUSIONS: Our results suggest that a simple automated alert could identify more than 40% of critically ill patients prescribed inappropriate antibiotic therapy for healthcare-associated infections. These data suggest that an opportunity exists to employ hospital informatics systems to improve the prescription of antibiotic therapy in ICU patients with suspected healthcare-associated infections.

Role of new drugs for management of atrial fibrillation.

OBJECTIVE: To evaluate the role of newer agents in the management of atrial fibrillation (AF). DATA SOURCES: EMBASE and MEDLINE were searched (up to June 2012) combining medication names with atrial fibrillation, humans, clinical trials, and pharmacoeconomic. References of the articles identified and www.clinicaltrials.gov were also reviewed. STUDY SELECTION AND DATA EXTRACTION: Studies were limited to the English language with clinical or pharmacoeconomic end points followed by the consensus of 3 authors. DATA SYNTHESIS: Formulated to reduce some of the adverse effects associated with amiodarone by removing the iodine component, dronedarone has improved clinical outcomes over placebo when used in paroxysmal or persistent AF; however, it is less efficacious than amiodarone. Worse outcomes with dronedarone have been seen in patients with heart failure or permanent AF. It has not been compared to antiarrhythmic agents other than amiodarone, and pharmacoeconomic evaluations are lacking. Dabigatran 150 mg is superior to warfarin in preventing stroke or systemic embolism and has been associated with lower rates of vascular-associated mortality. Although the rates of major bleeding were not significantly different between the 2 agents, gastrointestinal bleeding and myocardial infarction occurred more frequently with dabigatran. Dabigatran appears to have the most pharmacoeconomic benefit over warfarin in patients with a higher risk of stroke. Rivaroxaban is noninferior to warfarin for the prevention of stroke and systemic embolism, with no difference in the rates of major bleeding. Cost-effectiveness studies have not been performed with this agent at this time. In patients with AF who were not suitable candidates for warfarin, apixaban is superior to aspirin in preventing stroke or systemic embolism without increasing the risk for major bleeding. Additionally, apixaban is superior to warfarin in preventing stroke or systemic embolism, results in fewer bleeding events, and is associated with lower mortality. Apixaban is not cost-effective against aspirin when used for a short duration but gains superiority with prolonged use or in patients with higher risks of stroke. Additionally, apixaban appears to offer a pharmacoeconomic advantage over warfarin at no to minimal cost. Each new anticoagulant lacks a reversal agent and an assay to detect the presence of the anticoagulant, as well as long-term data when used in the clinical setting. CONCLUSIONS: Use of dronedarone should be limited to patients with paroxysmal or persistent AF and should not be used in patients with heart failure or with permanent AF. Newer antithrombotic agents appear to be promising alternatives for the prevention of stroke in patients with AF; however, more data are needed to understand their role.