A Review of Inotropes and Inopressors for Effective Utilization in Patients With Acute Decompensated Heart Failure.

ABSTRACT: Inotropes and inopressors are often first-line treatment in patients with cardiogenic shock. We summarize the pharmacology, indications, and contraindications of dobutamine, milrinone, dopamine, norepinephrine, epinephrine, and levosimendan. We also review the data on the use of these medications for acute decompensated heart failure and cardiogenic shock in this article.

Is it equivalent? Evaluation of the clinical activity of single agent Lipodox® compared to single agent Doxil® in ovarian cancer treatment.

BACKGROUND: In response to the critical shortage of liposomal doxorubicin (Doxil®) in the United States, the Food and Drug Administration (FDA) approved temporary importation of doxorubicin hydrochloride liposome (Lipodox®). The objective was to compare toxicity and clinical activity of Lipodox® with Doxil®. METHODS: Recurrent ovarian cancer patients who received Lipodox® were compared 3:1 to matched control Doxil® patients who had received Doxil®. Patients were matched based on age, stage, dose, platinum sensitivity, and prior treatments from an existing de-identified database. Patients receiving combination regimens were excluded. RESULTS: The data from 40 Lipodox® patients was compared to 120 matched control Doxil® patients. In this study, 17 (42.5%) of the Lipodox® patients were switched to Doxil®. The overall response rate Lipodox® was 4.3% (1/23) compared to 18% (20/111) in matched control Doxil® patients. In the platinum-sensitive patients, 100% progressed in the Lipodox® group compared to 78.4% in matched control Doxil® patients. The mean time to progression was 4.1 ± 2.8 months for Lipodox® and 6.2 ± 7.2 months in control Doxil®s (p = 0·25). Toxicity was similar in the Lipodox® group and control Doxil® group. CONCLUSION: Lipodox® for treatment of recurrent ovarian cancer did not appear to have equivalent efficacy compared to Doxil®. A prospective clinical study is warranted before Lipodox® can be deemed equivalent substitution for Doxil®.

Stability study of carboplatin infusion solutions in 0.9% sodium chloride in polyvinyl chloride bags.

BACKGROUND AND PURPOSE: Carboplatin is a platinum-containing compound with efficacy against various malignancies. The physico-chemical stability of carboplatin in dextrose 5% water (D5W) has been thoroughly studied; however, there is a paucity of stability data in clinically relevant 0.9% sodium chloride infusion solutions. The manufacturer's limited stability data in sodium chloride solutions hampers the flexibility of carboplatin usage in oncology patients. Hence, the purpose of this study is to determine the physical and chemical stability of carboplatin-sodium chloride intravenous solutions under different storage conditions. METHODS: The physico-chemical stability of 0.5 mg/mL, 2.0 mg/mL, and 4.0 mg/mL carboplatin-sodium chloride solutions prepared in polyvinyl chloride bags was determined following storage at room temperature under ambient fluorescent light and under refrigeration in the dark. Concentrations of carboplatin were measured at predetermined time points up to seven days using a stability-indicating high-performance liquid chromatography method. RESULTS: All tested solutions were found physically stable for at least seven days. The greatest chemical stability was observed under refrigerated storage conditions. At 4℃, all tested solutions were found chemically stable for at least seven days, with nominal losses of ≤6%. Following storage at room temperature exposed to normal fluorescent light, the chemical stability of 0.5 mg/mL, 2.0 mg/mL, and 4.0 mg/mL solutions was three days, five days, and seven days, respectively. CONCLUSION: The extended physico-chemical stability of carboplatin prepared in sodium chloride reported herein permits advance preparation of these admixtures, facilitating pharmacy utility and operations. Since no antibacterial preservative is contained within these carboplatin solutions, we recommend storage, when prepared under specified aseptic conditions, no greater than 24 h at room temperature or three days under refrigeration.

Potential Association of Holidays on Internationalized Normalized Ratio in Warfarin-Users at a Multidisciplinary Clinic.

Background: Warfarin is approved by the United States Food and Drug Administration for numerous clinical indications. The effectiveness of warfarin is highly dependent on the time-in-therapeutic range based on the international normalized ratio (INR) goal, which may be altered by changes in diet, alcohol intake, concomitant drugs, and travel, all of which are prevalent during the holidays. At this time, there are no published studies assessing the impact of holidays on INR in warfarin-users. Methods: A retrospective chart review was conducted on all adult patients taking warfarin and managed at a multidisciplinary clinic. Patients were included if they were taking warfarin at home regardless of indication for anticoagulation. The INR pre- and post-holiday was assessed. Results: Of a total of 92 patients, the mean age was 71.5 ± 14.3 years, and most patients were on warfarin with an INR goal of 2 - 3 (89%). There were significant differences in INR before and after Independence Day (2.55 vs. 2.81, P = 0.043) and Columbus Day (2.39 vs. 2.82, P < 0.001). The remaining holidays showed no significant differences in INR before and after each respective holiday. Conclusions: There may be factors related to Independence and Columbus Day that are increasing the level of anticoagulation in warfarin-users. Although the mean post-holiday INR values, in essence, maintained within the typical target of 2 - 3, our study underscores the specialized care that is warranted in higher risk patients to prevent a continued increase in INR and subsequent toxicities. We hope our results would be hypothesis-generating and aid in the development of larger, prospective evaluations to validate the findings of our present study.

Clofarabine in the treatment of newly diagnosed acute myeloid leukemia in older adults.

OBJECTIVE: To review the literature evaluating the efficacy and tolerability of clofarabine, a second-generation purine nucleoside analogue, for the treatment of previously untreated acute myeloid leukemia (AML) in older adults. DATA SOURCE: A literature search of the PubMed database (1972-October 2011) using the search terms clofarabine and acute myeloid leukemia was performed. STUDY SELECTION AND DATA EXTRACTION: All relevant English-language articles were reviewed, and clinical trials with patients aged 50 years or older who were newly diagnosed with AML were included. DATA SYNTHESIS: Two studies evaluating clofarabine as monotherapy and 2 studies evaluating clofarabine in combination with cytarabine were reviewed. Clofarabine demonstrated activity in older adults with previously untreated AML. Response rates and median overall survival (OS) for patients receiving clofarabine were similar to those reported for conventional intensive chemotherapy regimens. Responses to the 2 types of treatment remained similar in the presence of unfavorable prognostic factors, such as secondary AML or adverse cytogenetics. Although clofarabine was associated with a lower induction mortality rate versus intensive chemotherapy regimens, a significant percentage of patients experienced severe complications, including sepsis. Compared to single-agent clofarabine, response rates and median OS were higher for clofarabine combined with cytarabine. CONCLUSIONS: Based on published data, adverse effect profiles, and cost, clofarabine may be an appropriate alternative to intensive chemotherapy regimens in certain subsets of older patients with newly diagnosed AML. These include patients with a baseline decreased performance status or history of cardiovascular disease who may not tolerate anthracyclines, which are typically a component of most intensive chemotherapy regimens. Additional randomized controlled trials are needed to directly compare the efficacy of clofarabine with that of intensive chemotherapy regimens and to evaluate the potential benefit of combining clofarabine with cytarabine.

The Usage of Concomitant Beta-Blockers with Vasopressors and Inotropes in Cardiogenic Shock.

Vasopressors and inotropes (Vs/Is) are widely used in the treatment of cardiogenic shock (CS). Despite improvements in hemodynamic variables and end-organ perfusion, these agents have been associated with an increase in mortality, potentially due to the increased risk of tachyarrhythmias-which we hypothesize may be mitigated by beta-blockers (BBs). We conducted a retrospective chart review of patients who received a V/I (dobutamine, milrinone, dopamine, and norepinephrine) for CS. The primary objective was to assess the effect of BB in patients receiving Vs/Is for CS. In our final analysis of 227 patients, those in the BB group were younger, were more likely to have acute coronary syndrome as the reason for admission, had more reduced left ventricular ejection fraction, were more likely to have coronary artery disease and atrial fibrillation as pre-existing co-morbidities, and had a lower rate of in-hospital mortality. Nevertheless, in our multivariable logistic regression analysis, concurrent BB usage with a V/I was not associated with a reduction in in-hospital mortality. Our present study sheds light on the importance and urgency of large, carefully designed clinical studies to optimize inpatient medical therapy, particularly evaluating the combination of V/I and BB, in this high-risk patient population.

Association of Sacubitril/Valsartan with Metabolic Parameters in Patients with Reduced Ejection Fraction Heart Failure at a Multidisciplinary Clinic.

Background: Sacubitril/valsartan was approved for New York Heart Association (NYHA) class II-IV heart failure with reduced ejection fraction (HFrEF) in 2015, based on the results of the PARADIGM-HF trial, which showed a reduction in cardiovascular (CV) death and heart failure hospitalization, compared with enalapril. A subsequent subgroup analysis of the trial showed glycemic improvement for patients on sacubitril/valsartan compared with those on enalapril. Methods: This was a retrospective observational study at the Loma Linda University (LLU) International Heart Institute (IHI). The aim was to evaluate the association of sacubitril/valsartan with glycemic index and other metabolic parameters, including change in hemoglobin A1C (HbA1C), blood pressure (BP), ejection fraction (EF), body weight, and lipid profile from baseline and at 3, 6, and 12 months. The rates of CV-related hospitalizations and total hospitalizations were also assessed. Results: The change in mean HbA1C from baseline was not significantly different at 1 year (P = 0.993). The mean EF was significantly higher and the mean diastolic BP was significantly lowered. Body weight and lipid parameters remained unchanged. Both the rates of CV-related hospitalizations and total hospitalizations were significantly lowered. For the prespecified subgroup analysis of diabetic HFrEF patients, the mean HbA1C was nonsignificant at 12 months (mean difference -0.48, P = 0.993). Conclusion: A non-significant reduction in HbA1C was associated in HFrEF patients with diabetes mellitus. Large randomized trials are needed to confirm our findings regarding the potential metabolic benefits of sacubitril/valsartan.

Safety and Efficacy of Direct Oral Anticoagulants for Atrial Fibrillation in Patients with Renal Impairment.

Direct oral anticoagulants (DOACs) are gaining popularity for patients with nonvalvular atrial fibrillation (AF) for stroke prevention. Less bleeding risk with comparable stroke prevention compared to warfarin was shown. DOACs have predictable anticoagulant effects, infrequent monitoring requirements and less drug-food interactions compared to warfarin. However, safety and efficacy data of DOACs in patients with chronic kidney disease (CKD) are limited. This is a retrospective study to evaluate thromboembolic and bleeding events in patients with AF (with/without CKD) in October 2010 and July 2017. A total of 495 patients were included and only 150 patients had CKD. Our study found that patients with renal impairment on a DOAC do not have a higher incidence of bleeding events. It showed significant increase in thromboembolic events in CKD patients with dabigatran compared to CKD patients with apixaban with odds ratio of 6.58 (95%CI 1.35-32.02, p = 0.02).

Review of Direct Oral Anticoagulants and Guide for Effective Drug Utilization.

Direct oral anticoagulants (DOACs) have been developed as a viable and in some cases superior alternative to warfarin. These agents have overcome some of the limitations of warfarin, which has a narrow therapeutic window and many food and drug interactions. DOACs have been demonstrated to have a more predictable and reliable pharmacology and, unlike warfarin, do not require frequent monitoring of anticoagulant effect. For these reasons, the use of DOACs is increasing. Despite the many positive attributes of these agents, limitations and contraindications do exist. An understanding of the pharmacology, indications, and contraindications is therefore crucial for effective patient management. We review the available agents to aid in effective drug utilization.

A multidisciplinary atrial fibrillation clinic.

BACKGROUND: Reports in the literature indicate that specialty clinics focusing on management of patients with specific chronic disorders have a significant positive impact on patient outcomes. Atrial fibrillation (AF), one of the most common forms of cardiac arrhythmia, affects millions of patients. Outcome data regarding the impact of managing patients with AF are limited. We established a specialty clinic focusing on management of patients with AF. The objective of our study was to evaluate the outcomes of treating AF patients in this clinic. METHODS: A team consisting of electrophysiologists and pharmacists designed a specific plan for managing and educating patients. This plan consisted of evaluation, implementation of an individualized treatment plan, patient education, medication management, and follow-up care. We reviewed the outcomes of patients who had clinic visits between November 2011 and March 2012. The primary outcome was the incidence of AF-related hospitalizations and stroke. RESULTS: Seventy one patients were included in the analysis. Out of 71 patients, we identified 17 (23.9%) patients who were hospitalized. Two of these 17 hospitalized patients had ischemic stroke events. CONCLUSION: When compared to published data in the existing literature, managing AF patients in specialty clinics reduces the incidence of AF-related hospitalizations and stroke.