Medicine and Health Sciences Commons^™

Andexanet Alfa Versus Pcc Products For Factor Xa Inhibitor Bleeding: A Systematic Review With Meta-Analysis, C. Michael White, Kimberly Snow Caroti, Youssef Bessada, Adrian V. Hernandez, William L. Baker, Paul P. Dobesh, Heleen Van Haalen, Kirsty Rhodes, Craig I. Coleman

Journal Articles: Pharmacy Practice

Previous meta-analyses assessed andexanet alfa (AA) or prothrombin complex concentrate (PCC) products for the treatment of Factor Xa inhibitor (FXaI)-associated major bleeding. However, they did not include recent studies or assess the impact of the risk of bias. We conducted a systematic review with meta-analysis on the effectiveness of AA versus PCC products for FXaI-associated major bleeding, inclusive of the studies' risk of bias. PubMed and Embase were searched for comparative studies assessing major bleeding in patients using FXaI who received AA or PCC. We used the Methodological Index for NOn-Randomized Studies (MINORS) checklist and one question from the Joanna …

Lower Mortality With Andexanet Alfa Vs 4-Factor Prothrombin Complex Concentrate For Factor Xa Inhibitor-Related Major Bleeding In A U.S. Hospital-Based Observational Study, Paul P. Dobesh, Gregory J. Fermann, Mary J. Christoph, Bruce Koch, Eva Lesén, Hungta Chen, Belinda Lovelace, Theresa Dettling, Mark Danese, Julie Ulloa, Sherry Danese, Craig I. Coleman

Journal Articles: Pharmacy Practice

BACKGROUND: Well-designed studies with sufficient sample size comparing andexanet alfa vs 4-factor prothrombin complex concentrate (4F-PCC) in routine clinical practice to evaluate clinical outcomes are limited.

OBJECTIVES: To compare in-hospital mortality in patients hospitalized with rivaroxaban- or apixaban-related major bleeding who were treated with andexanet alfa or 4F-PCC.

METHODS: An observational cohort study (ClinicalTrials.gov identifier: NCT05548777) was conducted using electronic health records between May 2018 and September 2022 from 354 U.S. hospitals. Inclusion criteria were age ≥18 years, inpatient admission with diagnosis code D68.32 (bleeding due to extrinsic anticoagulation), a record of use of the factor Xa inhibitors rivaroxaban or …

Treatment Of A Chemoresistant Neuroblastoma Cell Line With The Antimalarial Ozonide Oz513., Don W. Coulter, Timothy R. Mcguire, J. Graham Sharp, Erin M. Mcintyre, Yuxiang Dong, Xiaofang Wang, Shawn Gray, Gracey R. Alexander, Nagendra K. Chatuverdi, Shantaram Joshi, Xiaoyu Chen, Jonathan L. Vennerstrom

Journal Articles: Pharmacy Practice

BACKGROUND: Evaluate the anti-tumor activity of ozonide antimalarials using a chemoresistant neuroblastoma cell line, BE (2)-c.

METHODS: The activity of 12 ozonides, artemisinin, and two semisynthetic artemisinins were tested for activity against two neuroblastoma cell-lines (BE (2)-c and IMR-32) and the Ewing's Sarcoma cell line A673 in an MTT viability assay. Time course data indicated that peak effect was seen 18 h after the start of treatment thus 18 h pre-treatment was used for all subsequent experiments. The most active ozonide (OZ513) was assessed in a propidium iodide cell cycle flow cytometry analysis which measured cell cycle transit and apoptosis. …

Guidance For The Practical Management Of The Heparin Anticoagulants In The Treatment Of Venous Thromboembolism., Maureen A. Smythe, Jennifer Priziola, Paul P. Dobesh, Diane Wirth, Adam Cuker, Ann K. Wittkowsky

Journal Articles: Pharmacy Practice

Venous thromboembolism (VTE) is a serious and often fatal medical condition with an increasing incidence. Despite the changing landscape of VTE treatment with the introduction of the new direct oral anticoagulants many uncertainties remain regarding the optimal use of traditional parenteral agents. This manuscript, initiated by the Anticoagulation Forum, provides clinical guidance based on existing guidelines and consensus expert opinion where guidelines are lacking. This specific chapter addresses the practical management of heparins including low molecular weight heparins and fondaparinux. For each anticoagulant a list of the most common practice related questions were created. Each question was addressed using a …

Direct Oral Anticoagulants For The Prevention Of Stroke In Patients With Nonvalvular Atrial Fibrillation: Understanding Differences And Similarities., Paul P. Dobesh, John Fanikos

Journal Articles: Pharmacy Practice

The presence of atrial fibrillation (AF), the most common sustained cardiac arrhythmia, significantly increases the risk for stroke. Current guidelines recommend that the vitamin K antagonist warfarin or direct oral anticoagulants (DOACs), such as the approved direct thrombin inhibitor dabigatran and the approved direct factor Xa inhibitors apixaban, rivaroxaban, and edoxaban, should be used for thromboprophylaxis in patients with nonvalvular AF at risk for stroke or systemic embolic events (SEE). Warfarin, the mainstay of stroke prevention in AF, increases the risk of major bleeding. Furthermore, warfarin therapy comes with several limitations including frequent monitoring and the need for dose adjustments, …

Impact Of A High-Fat Meal On Assessment Of Clopidogrel-Induced Platelet Inhibition In Healthy Subjects., Paul P. Dobesh, Jamela F. Urban, Scott W. Shurmur, Julie H. Oestreich

Journal Articles: Pharmacy Practice

BACKGROUND: Ideal conditions for platelet reactivity testing are critical for optimal selection of a P2Y12 inhibitor. Data are inconsistent regarding the impact of high-fat meals on test assessment.

METHODS: Participants included 12 healthy subjects not taking antiplatelet drugs after a 12-hour fast. After baseline assessment, subjects were given a 600 mg dose of clopidogrel. Four hours later, maximum platelet inhibition was tested in the fasting state by light transmission aggregometry (LTA), VerifyNow P2Y12, vasodilator-stimulated phosphoprotein (VASP), and whole blood aggregometry (WBA). Subjects were then provided a high-fat meal, and platelet function was evaluated two hours later. Change in measured platelet …

New Oral Anticoagulants For The Treatment Of Venous Thromboembolism: Understanding Differences And Similarities., Paul P. Dobesh, John Fanikos

Journal Articles: Pharmacy Practice

Venous thromboembolism (VTE) is a major cause of morbidity, mortality, and healthcare expenditure. In the United States, approximately 0.1 % of the population experiences an initial VTE event each year. Anticoagulation therapy is the cornerstone of acute VTE treatment and for prevention of recurrent VTE events. Conventional anticoagulants, including heparin, low-molecular-weight heparins, fondaparinux, and vitamin K antagonists are widely used but have limitations. Newer oral anticoagulant agents, including direct thrombin inhibitors (e.g., dabigatran etexilate) and direct factor Xa inhibitors (e.g., rivaroxaban, apixaban, and edoxaban) have been developed to attempt to overcome some of the limitations of conventional anticoagulant therapy. These …

Ticagrelor: Pharmacokinetics, Pharmacodynamics, Clinical Efficacy, And Safety., Paul P. Dobesh, Julie H. Oestreich

Journal Articles: Pharmacy Practice

Dual antiplatelet therapy, composed of aspirin plus a P2Y12 -receptor antagonist, is the cornerstone of treatment for patients with acute coronary syndrome (ACS). A number of U.S. Food and Drug Administration-approved P2Y12 -receptor antagonists are available for treating patients with ACS, including the thienopyridine compounds clopidogrel and prasugrel. Ticagrelor, the first of a new class of antiplatelet agents, is a noncompetitive, direct-acting P2Y12 -receptor antagonist. Unlike the thienopyridine compounds, ticagrelor does not require metabolism for activity. Also, whereas clopidogrel and prasugrel are irreversible inhibitors of the P2Y12 receptor, ticagrelor binds reversibly to inhibit receptor signaling and subsequent platelet activation. In …

Clinical Use Of Rivaroxaban: Pharmacokinetic And Pharmacodynamic Rationale For Dosing Regimens In Different Indications., Toby Trujillo, Paul P. Dobesh

Journal Articles: Pharmacy Practice

Target-specific oral anticoagulants have become increasingly available as alternatives to traditional agents for the management of a number of thromboembolic disorders. To date, the direct Factor Xa inhibitor rivaroxaban is the most widely approved of the new agents. The dosing of rivaroxaban varies and adheres to specific schedules in each of the clinical settings in which it has been investigated. These regimens were devised based on the results of phase II dose-finding studies and/or pharmacokinetic modeling, and were demonstrated to be successful in randomized, phase III studies. In most cases, the pharmacodynamic profile of rivaroxaban permits once-daily dosing. A once-daily …