Deterioration free discharge comparison of andexanet-alfa and prothrombin complex concentrates (PCC) for reversal of factor Xa inhibitor associated bleeds.

Given the paucity of comparative efficacy data and the difference in cost between andexanet-alfa and prothrombin complex concentrates (PCC), debates continue regarding optimal cost-effective therapy for patients who present with major bleeding associated with oral factor Xa inhibitors. Available literature comparing the cost-effectiveness of the reversal agents is limited, and the large difference in price between therapy options has led many health systems to exclude andexanet-alfa from their formularies. To evaluate the clinical outcomes and cost of PCC compared to andexanet-alfa for patients with factor Xa inhibitor associated bleeds. We performed a quasi-experimental, single health system study of patients treated with PCC or andexanet-alfa from March 2014 to April 2021. Deterioration-free discharge, thrombotic events, length of stay, discharge disposition, and cost were reported. 170 patients were included in the PCC group and 170 patients were included in the andexanet-alfa group. Deterioration-free discharge was achieved in 66.5% of PCC-treated patients compared to 69.4% in the andexanet alfa-treated patients. 31.8% of PCC-treated patients were discharged home compared to 30.6% in the andexanet alfa-treated patients. The cost per deterioration-free discharge was $20,773.62 versus $5230.32 in the andexanet alfa and 4 F-PCC group, respectively. Among patients that experienced a bleed while taking a factor Xa inhibitor, there was no difference in clinical outcomes for patients treated with andexanet-alfa compared to PCC. Although there was no difference in the clinical outcomes, there was a significant difference in cost with andexanet-alfa costing approximately four times as much as PCC per deterioration-free discharge.

Incidence of Heparin-Induced Thrombocytopenia in Patients With Newly Implanted Mechanical Circulatory Support Devices.

BACKGROUND: Heparin exposure and device-related thrombocytopenia complicate the diagnosis of heparin-induced thrombocytopenia (HIT) in patients receiving mechanical circulatory support (MCS). To improve anticoagulation management for patients with newly implanted MCS devices, incidence of confirmed HIT needs to be further characterized. OBJECTIVES: The purpose of this study is to describe the incidence of HIT and clinical utility of the 4Ts score in patients with newly implanted MCS devices. METHODS: This is a retrospective analysis of MCS patients receiving unfractionated heparin from 2014 to 2017. The primary end point was incidence of laboratory-confirmed HIT. Strong positive, likely positive, low probability, and negative HIT categories were established based on heparin-induced platelet antibody (HIPA) and serotonin release assay (SRA). Secondary end points include characterization of platelet trends, argatroban use, incidence of HIT among each of the MCS devices, and utility of 4Ts score. RESULTS: A total of 342 patient encounters met inclusion criteria, of which 68 HIPA tests and 25 SRAs were ordered. The incidence of HIT was 0.88% (3/342) and 4.4% (3/68) in patients with suspected HIT. Of the 68 HIPA tests, 3 (4.4%) were considered strong positive and 3 of the 25 SRAs were positive. Median 4Ts score was 4 [2.5-4] and optical density 0.19 [0.11-0.54]. The positive predictive value for the 4Ts score was 0.15 (CI = 0.03-0.46) and negative predictive value, 0.93 (CI = 0.82-0.98). CONCLUSION AND RELEVANCE: HIT occurs infrequently with newly implanted MCS devices. The 4Ts score appears to have a high negative predictive value for ruling out HIT.

A systematic review of apixaban in prevention and treatment of cancer-associated venous thromboembolism.

BACKGROUND: Venous thromboembolism (VTE) is the second leading cause of death in patients with cancer after disease progression. Thus, timely initiation of anticoagulation after diagnosis of a VTE is required to prevent significant sequelae. Direct oral anticoagulants (DOACs) are newer anticoagulant options for cancer associated VTE (CA-VTE), which historically has been treated with low molecular weight heparin. OBJECTIVE: The objective of this study was to review the available literature evaluating the use of apixaban for CA-VTE. METHODS: A systematic review (following PRISMA Guidelines) of MEDLINE and EMBASE using the search terms "apixaban" AND "cancer" AND "VTE" was performed from database inception through May 20, 2020. Articles were eligible for inclusion if they were full articles fulfilling the following criteria: (1) randomized controlled trial (RCT) or prospective cohort study, or (2) subgroup analysis of an RCT, and (3) reported clinical outcomes associated with apixaban for prevention or treatment of VTE in patients with cancer. RESULTS: A total of 532 articles were identified. After duplicates were removed, 423 articles were screened, and 12 articles were eligible for full-text review. Of the 12 articles, 2 were excluded for having no comparator group, and 2 were excluded for being abstracts only. Ultimately, 8 articles met the inclusion criteria. CONCLUSIONS: The available literature supports the safety and efficacy of apixaban for the treatment and prevention of CA-VTE. With the recent publication of the CARAVAGGIO trial, we anticipate that apixaban will be uniformly recommended in national guidelines as a treatment option for CA-VTE.

Safety and efficacy of target-specific anticoagulants in patients with venous thromboembolism.

OBJECTIVE: To review the role of target-specific anticoagulants (TSACs) for the treatment of venous thromboembolism (VTE) and their associated efficacy and safety. DATA SOURCES: Peer-reviewed clinical trials, review articles, and relevant treatment guidelines were identified from MEDLINE (1966 to November 2014) using the following search terms: venous thromboembolism, vitamin K antagonist (VKA), target-specific anticoagulant, deep-vein thrombosis, pulmonary embolism. Results were limited to human trials published in English. Citations from articles were reviewed for additional references. STUDY SELECTION AND DATA EXTRACTION: Clinical trials evaluating VTE treatment were included. Trials that evaluated alternative end points were excluded. DATA SYNTHESIS: Patients with VTE have a high risk of developing recurrent events and subsequent death if not treated in an appropriate manner. TSACs have been evaluated in several large clinical trials in patients with acute VTE. These trials have shown positive outcomes when compared with VKAs for treatment of VTE in the general population. Paralleled with these results, TSACs had similar or lower rates of bleeding compared with VKAs. CONCLUSIONS: Taken together, available evidence suggests that TSACs produce similar clinical benefits with less bleeding incidence when compared with VKAs in the treatment of VTE. There are significant differences between each study investigating this class of medication for VTE treatment. Each TSAC has potential advantages, and to date, there has been no head-to-head trial comparing them.

Safety and efficacy of statins in patients with end-stage renal disease.

OBJECTIVE: To review statins in the prevention of cardiovascular disease (CVD) events and their associated safety in patients with end-stage renal disease (ESRD). DATA SOURCES: Peer-reviewed clinical trials, review articles, and treatment guidelines were identified from MEDLINE (1966-July 2013) using the following search terms: end stage renal disease, statin, HMG-CoA (hydroxymethylglutaryl-coenzyme A) reductase inhibitor, chronic kidney disease, cardiovascular outcomes, and cardiovascular disease. Results were limited to human trials published in English. Citations from articles were reviewed for additional references. STUDY SELECTION AND DATA EXTRACTION: Only clinical trials evaluating cardiovascular end points of statins used in patients with ESRD were included. DATA SYNTHESIS: In patients with ESRD, CVD is the leading cause of death. Statin therapy has been evaluated in 3 clinical trials in patients with ESRD. The 4D and AURORA trials failed to show a benefit with statin therapy, and the SHARP trial, although positive, also included patients with earlier stages of chronic kidney disease. Despite the lack of efficacy, statin therapy was well tolerated. The cause of cardiovascular death in this patient population may not be a result of atherosclerotic events and possibly dependent on the type of renal replacement therapy. For patients on hemodialysis, lipid profiles may not be amenable to statin therapy. CONCLUSIONS: Statin therapy has failed to significantly alter the course of CVD events in patients with ESRD. Evidence supports avoiding the routine use of statins in this patient population and instead reserving them for patients with elevated cholesterol levels or those with recent CVD events.

Overview of betrixaban and its role in clinical practice.

PURPOSE: The role of betrixaban in the prevention of venous thromboembolism (VTE) in acutely medically ill patients and its efficacy and safety profiles are reviewed. SUMMARY: Acutely medically ill patients have a high risk of developing VTE during hospitalization, and this risk continues into the postdischarge phase. Extended-duration betrixaban therapy has been evaluated in a large clinical trial (the APEX trial) and in a meta-analysis of pooled data on acutely medically ill patients. These studies have shown positive outcomes when betrixaban was compared with conventional-duration subcutaneous enoxaparin therapy for prevention of VTE in acutely medically ill patients. In parallel with these results, oral betrixaban therapy was found to be associated with a rate of major bleeding comparable to that associated with subcutaneous enoxaparin therapy; however, betrixaban use was associated with a higher cumulative rate of major and clinically relevant nonmajor bleeding. In the APEX trial, the primary endpoint was not met in 1 of the prespecified cohorts, but betrixaban appeared to confer benefit in another cohort and in the overall study population. Certain populations of patients, including the elderly, are at high risk for bleeding (mainly attributable to altered pharmacokinetics and polypharmacy); such patients are not appropriate candidates for extended-duration betrixaban therapy. Betrixaban can be a potential option for VTE prevention in medical patients; however, drug interaction potential and third-party coverage should be evaluated prior to prescribing. CONCLUSION: Betrixaban is an oral option for VTE prevention in medical patients.

Assessing the potential of e-mail for communicating drug therapy recommendations to physicians in patients with heart failure and ventricular-assist devices.

PURPOSE: This project explores electronic mail (e-mail) as a potential medium for pharmacists to communicate pharmacotherapy interventions to prescribers. METHODS: This retrospective descriptive analysis was conducted at an urban, academic teaching hospital. The pharmacist attempted a drug therapy intervention via e-mail when unable to make face-to-face contact with the attending physician. Eligible patients for this project were admitted to the advanced heart failure (HF) team between December 1, 2010, and July 31, 2011, and had at least 1 attempted e-mail intervention. The primary outcome was the number of accepted interventions, while the secondary end point was the time until a physician e-mail response. RESULTS: A total of 51 e-mail interventions were attempted on 29 patients (mean age = 53, 24% caucasian, 59% male, 69% left ventricular-assist device [VAD]). Overall, of the total 51 interventions,44 (86.3%) were accepted. The average time to a physician e-mail response was 41 minutes. Initiation of drug therapy and changing dose and route or frequency accounted for the most frequent intervention (33%). The most common drug classes involved in the e-mail interventions were angiotensin-converting enzyme inhibitors (15.7%), loop diuretics (9.8%), and antiplatelet agents (7.8%). CONCLUSION: Clinical pharmacists with well-established physician relationships can effectively implement timely drug therapy recommendations using e-mail communications in patients with advanced HF or VADs.