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.

Sodium-Glucose Cotransporter 2 Inhibitors Among Heart Failure With Mildly Reduced and Preserved Ejection Fraction.

OBJECTIVE: Results from large placebo-controlled randomized trials in patients with heart failure with mid-range ejection fraction (HFmrEF) and HF with preserved EF (HFpEF) have become available recently. This article discusses results of these clinical trials. DATA SOURCES: Peer-reviewed articles were identified from MEDLINE (1966 to December 31, 2022) using search terms dapagliflozin, empagliflozin, SGLT-2Is, HFmrEF, and HFpEF. STUDY SELECTION AND DATA EXTRACTION: Eight completed, pertinent clinical trials were included. DATA SYNTHESIS: EMPEROR-Preserved, and DELIVER demonstrated that empagliflozin and dapagliflozin reduce CV death and heart failure hospitalization (HHF) in patients with HFmrEF and HFpEF, with/without diabetes when added to a standard heart failure (HF) regimen. The benefit is primarily due to reduction in HHF. Additional data from post hoc analyses of trials of dapagliflozin, ertugliflozin, and sotagliflozin suggest that these benefits may be a class effect. Benefits appear greatest in patients with left ventricular ejection fraction 41% up to about 65%. RELEVANCE TO PATIENT CARE AND CLINICAL PRACTICE: While many pharmacologic treatments have been proven to reduce mortality and improve cardiovascular (CV) outcomes in people with HFmrEF and HF with reduced EF (HFrEF), there are few therapy which improve CV outcome in people with HFpEF. SGLT-2I become one of the first class of pharmacologic agent that can be used to reduce HHF and CV mortality. CONCLUSION: Studies showed that empagliflozin and dapagliflozin reduce the combined risk of CV death or HHF in patients with HFmrEF and HFpEF when added to a standard HF regimen. Given that benefit has now been demonstrated across the spectrum of HF, SGLT-2Is should be considered one of the standard HF pharmacotherapy.

Pharmacist hypertension management using an electronic health record-based approach.

OBJECTIVES: To evaluate the impact of the chronic medication optimization pharmacist (CMOP) program on blood pressure (BP) control and time to goal compared with usual care in the ambulatory care setting. STUDY DESIGN: This was a retrospective cohort study that included patients from June 2018 to June 2020 who were seen in an ambulatory care clinic for hypertension management. METHODS: Patients aged 18 to 80 years were divided into 2 cohorts based on hypertension management by usual care or the CMOP program. Patients were enrolled in the CMOP program either by referral or identification via a data analytics tool. The primary outcome assessed the proportion of patients within BP goal (< 140/90 mm Hg) at 3 months. Secondary outcomes assessed the proportion of patients within goal at 6 months, time and number of visits to goal, and adherence (CMOP cohort only). RESULTS: The primary end point demonstrated a greater proportion of patients within goal in the CMOP cohort compared with usual care (69.4% vs 42.3%; P < .001). The CMOP cohort also displayed a greater proportion of patients achieving goal within 6 months (75.7% vs 60.4%; P = .014) and faster time to goal (42.99 vs 63.12 days; P = .002), but more visits (1.67 vs 1.18; P = .001). Lastly, adherence improved from 50.4% to 72.1% in the patients with a documented adherence assessment in the pharmacist group (P = .03). CONCLUSIONS: The pharmacist intervention improved BP control in a primarily African American patient population compared with usual care. Future studies should assess the sustainability of this intervention.

Optimizing preoperative antibiotics in patients with ß-lactam allergies: A role for pharmacy.

PURPOSE: Patients with a reported ß-lactam allergy (BLA) are often given alternative perioperative antibiotic prophylaxis, increasing risk of surgical site infections (SSIs), acute kidney injury (AKI), and Clostridioides difficile infection (CDI). The purpose of this study was to implement and evaluate a pharmacist-led BLA clarification interview service in the preoperative setting. METHODS: A pharmacist performed BLA clarification telephone interviews before elective procedures from November 2018 to March 2019. On the basis of allergy history and a decision algorithm, first-line preoperative antibiotics, alternative antibiotics, or allergy testing referral was recommended. The pharmacist intervention (PI) group was compared to a standard of care (SOC) group who underwent surgery from November 2017 to March 2018. RESULTS: Eighty-seven patients were included, with 50 (57%) and 37 (43%) in the SOC and PI groups, respectively. The most common surgeries included orthopedic surgery in 41 patients (47%) and neurosurgery in 17 patients (20%). In the PI group, all BLA labels were updated after interview. Twenty-three patients were referred for allergy testing, 12 of the 23 (52%) completed BLA testing, and penicillin allergies were removed for 9 of the 12 patients. Overall, 28 of the 37 (76%) pharmacy antibiotic recommendations were accepted. Cefazolin use significantly increased from 28% to 65% after the intervention (P = 0.001). SSI occurred in 5 (10%) patients in the SOC group and no patients in the PI group (P = 0.051). All of these SSIs were associated with alternative antibiotics. Incidence of AKI and CDI was similar between the groups. No allergic reactions occurred in either group. CONCLUSION: Implementation of a pharmacy-driven BLA reconciliation significantly increased ß-lactam preoperative use without negative safety outcomes.

Focused Updates: SGLT2 Inhibitors in Patients With Heart Failure and/or Chronic Kidney Disease.

Sodium-glucose cotransporter (SGLT2) inhibitors have demonstrated cardiovascular (CV) benefits in large-scale clinical trials of people who have type 2 diabetes and either established CV disease or multiple CV risk factors. These studies also indicated early signals in benefiting heart failure (HF) patients and those with chronic kidney diseases. This article reviews recent and future clinical studies that focus on evaluation of the use of SGLT2 inhibitors in HF management and renal protection.

Managing Diabetes and Preventing Heart Disease: Have We Found a Safe and Effective Agent?

OBJECTIVE: While improving glycemic control with antihyperglycemics has been demonstrated to reduce microvascular complications, the benefits of reduction in cardiovascular diseases (CVDs) have not been demonstrated with older agents. This article reviews current evidence of the CV outcomes of newer antihyperglycemics approved since 2008. DATA SOURCES: Peer-reviewed articles were identified from MEDLINE (1966 to October 31, 2018) using search terms exenatide, liraglutide, lixisenatide, dulaglutide, semaglutide, alogliptin, linagliptin, saxagliptin, sitagliptin, canagliflozin, dapagliflozin, empagliflozin, mortality, myocardial infarction (MI), heart failure (HF), and stroke. STUDY SELECTION AND DATA EXTRACTION: A total of 12 pertinent double-blinded randomized controlled trials were included. DATA SYNTHESIS: Liraglutide, empagliflozin, and canagliflozin have been shown in patients with CV diseases and high risk of developing CV disease to be superior to placebo in improving CV outcomes. Saxagliptin and alogliptin have both been demonstrated to increase HF hospitalization, whereas sitagliptin has not. Relevance to Patient Care and Clinical Practice: In contrast to older-generation antihyperglycemics, selected new antihyperglycemic agents have been shown to be superior to placebo in improving CV outcomes. Clinicians may now be able to provide high-risk patients agents that not only help in providing glycemic control, but also prevent both macrovascular and microvascular complications. CONCLUSION: Liraglutide, empagliflozin, and canagliflozin have been shown to be superior to placebo in improving CV outcomes. However, there are differences among agents in terms of HF and peripheral arterial disease outcomes. Future studies should focus on evaluating other clinical CV outcomes in patients without existing CVD and perhaps single drug regimens for diabetes.

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.

Creating objective and measurable postgraduate year 1 residency graduation requirements.

PURPOSE: The process of developing objective and measurable postgraduate year 1 (PGY1) residency graduation requirements and a progress tracking system is described. SUMMARY: The PGY1 residency accreditation standard requires that programs establish criteria that must be met by residents for successful completion of the program (i.e., graduation requirements), which should presumably be aligned with helping residents to achieve the purpose of residency training. In addition, programs must track a resident's progress toward fulfillment of residency goals and objectives. Defining graduation requirements and establishing the process for tracking residents' progress are left up to the discretion of the residency program. To help standardize resident performance assessments, leaders of an academic medical center-based PGY1 residency program developed graduation requirement criteria that are objective, measurable, and linked back to residency goals and objectives. A system for tracking resident progress relative to quarterly progress targets was instituted. Leaders also developed a focused, on-the-spot skills assessment termed "the Thunderdome," which was designed for objective evaluation of direct patient care skills. Quarterly data on residents' progress are used to update and customize each resident's training plan. Implementation of this system allowed seamless linkage of the training plan, the progress tracking system, and the specified graduation requirement criteria. CONCLUSION: PGY1 residency requirements that are objective, that are measurable, and that attempt to identify what skills the resident must demonstrate in order to graduate from the program were developed for use in our residency program. A system for tracking the residents' progress by comparing residents' performance to predetermined quarterly benchmarks was developed.

Cardiovascular Pharmacokinetics, Pharmacodynamics, and Pharmacogenomics for the Clinical Practitioner.

Current clinical cardiovascular practice requires a clinician to have a strong foundation in multiple aspects of pharmacology. Modern cardiovascular regimens are complex, and optimal management, application of evolving guidelines, and adoption of new therapies build off a more basic understanding of pharmacokinetics and pharmacodynamics. In addition, it is likely time to add a third pillar into this discussion, the expanding field of pharmacogenomics referring to the genetic influences on drug response. This field has increasing applications in medicine and clearly holds significant promise for cardiovascular disease management. Awareness of pharmacogenomic advances and the fundamentals of pharmacokinetics and pharmacodynamics can help the clinician more easily deliver great care. Here we attempt to briefly summarize and simplify key concepts of pharmacokinetics, pharmacodynamics, and pharmacogenomics relevant to the cardiovascular disease practitioner.

Impact of Platelet Functional Assays on the Cost of Treating Suspected Heparin-Induced Thrombocytopenia.

OBJECTIVES: To investigate the potential cost savings of using functional platelet assays to confirm the diagnosis of heparin-induced thrombocytopenia (HIT). METHODS: This was a single-center study conducted in the United States. We performed a retrospective cost of illness analysis of suspected HIT, comparing patients with the serotonin release assay (SRA) ordered as part of their diagnostic evaluation to those who did not. The primary clinical end point was a composite of mortality and major bleed. RESULTS: A total of 147 patients met the study's inclusion criteria. An SRA was ordered in 53 patients of whom 17% were positive. Overall, SRA use did not reduce the composite primary clinical end point (32.1% vs 33%, P = .911). Also, there was no difference in the total cost of hospital stay (US $84781.1 vs US $78534.4, P = .409) nor in the direct medical costs related to HIT management (US $7473.5 vs US $8402.4, P = .393). Early ordering of the SRA (within 48 hours) was associated with shorter length of stay (20 vs 27 days, P = .029) but without a difference in cost of treatment. CONCLUSION: The use of SRA did not reduce the costs or improve clinical outcomes in patients with suspected HIT.

Variations in pharmacy-based transition-of-care activities in the United States: a national survey.

PURPOSE: A national survey was conducted to assess pharmacist roles in transition-of-care (TOC) activities in the United States. METHODS: An online survey was sent to 1246 pharmacy directors who were members of the American Society of Health-System Pharmacists to assess their involvement in TOC activities including medication reconciliation, admission histories, medication counseling, and postdischarge follow-up; pharmacy student and pharmacy technician involvement in TOC activities; the use of technology to facilitate TOC activities; and barriers to performing such activities. RESULTS: A total of 393 respondents completed the survey (31.5% response rate). Twenty-seven percent of respondents indicated that pharmacists complete medication histories on admission, and 5% indicated that pharmacy technicians complete medication histories. Most respondents indicated that pharmacists do not routinely or consistently provide patients with tools to facilitate medication adherence before hospital discharge and that pharmacists do not routinely or consistently follow up with patients after discharge. Fifty-six percent of respondents indicated that pharmacists provide patient education for specific medications or for medications for specific diseases. Few respondents indicated that student pharmacists are involved with TOC activities. Most respondents either agreed or strongly agreed that it is important for pharmacists to be involved in TOC activities for hospitalized patients. CONCLUSION: Approximately one third of survey respondents indicated that pharmacists complete medication histories. Most respondents indicated that pharmacists do not routinely or consistently provide patients with tools to facilitate medication adherence before hospital discharge or follow up with patients after discharge. Lack of pharmacy staff resources and insufficient recognition of the value of pharmacists' provision of TOC by health care executives, medical staff, nursing staff, and other health care professionals were the most frequently cited barriers to pharmacists assuming more significant roles in the TOC at the respondent's institution.

Epidemiology and outcomes associated with anemia during long-term support with continuous-flow left ventricular assist devices.

BACKGROUND: The purpose of this study was to define the prevalence and clinical ramifications of anemia in patients implanted with a continuous-flow left ventricular assist device (CF-LVAD). METHODS AND RESULTS: Patients implanted with a CF-LVAD from January 1, 2008, to April 30, 2012, were included in this retrospective cohort study. The primary outcome was the prevalence of anemia throughout the 1st year of device support. Secondary end points included the impact of anemia on rates of readmission to hospital and mortality. Ninety-one patients were included; the prevalence of anemia 360 days after implantation was significantly reduced compared with baseline (61.4% vs 79.1%, respectively; P = .032); 65.4% of anemic patients and 34.6% of nonanemic patients were readmitted at least once (P = .067). The median number of readmissions in the anemic compared with the nonanemic group was 4 (interquartile range [IQR] 2-6) versus 1.5 (IQR 1-3), respectively (P < .001). Furthermore, among those who experienced >3 readmissions during the 1st year, 19 were anemic compared with 1 patient who was not anemic (P < .001). CONCLUSIONS: Anemia remains a prevalent condition while on CF-LVAD support and is associated with a significant increase in the number of hospital readmissions.

Effective anticoagulation for a percutaneous ventricular assist device using a heparin-based purge solution.

OBJECTIVE: To report on a series of patients who were successfully anticoagulated with a novel protocol including a heparin-based purge solution. CASE SUMMARY: Four patients were supported for a total of 300 hours on the new Impella anticoagulation protocol, which was based on our current nurse-driven cardiology heparin protocol. Three patients were in cardiogenic shock after acute myocardial infarction, and 1 patient was in shock from severe aortic valvular disease. Despite prolonged cardiogenic shock, none of the patients developed significant renal or liver dysfunction while on device support. All 4 patients survived to hospital discharge, and there were no significant bleeding or thromboembolic events. Furthermore, there were no device malfunctions or clotting events within with pump motors. Despite frequent changes to the purge solution flow rate by the Automated Impella Controller, the patients in our cohort had relatively stable activated partial thromboplastin time values. DISCUSSION: Our novel anticoagulation protocol, which incorporates the heparin included in the purge solution into the total hourly heparin dosage, was successful in the first cohort of patients receiving extended Impella support for cardiogenic shock. Our case series also highlights that the Automated Impella Controller makes frequent adjustments to the purge solution, which depending on the heparin concentration, can result in significant fluctuations in the patient's total hourly heparin dosage. Furthermore, balancing the heparin in the purge solution with the intravenous heparin is important to ensuring adequate anticoagulation in patients supported by the Impella devices in the intensive care unit. CONCLUSIONS: Development of a standardized anticoagulation protocol for the Impella device that factors the heparin-based purge into the total heparin dosage and makes appropriate adjustments based on the fluctuating rate of the purge solution can provide effective anticoagulation to patients receiving extended circulatory support from this device.

Management of bleeding and reversal strategies for oral anticoagulants: clinical practice considerations.

PURPOSE: Currently available clinical data and optimal strategies for reversing oral anticoagulants in patients who are bleeding or need an urgent invasive procedure or operation are reviewed. SUMMARY: Bleeding from oral anticoagulants, including new target-specific oral agents (TSOAs), is a common cause of morbidity and mortality, especially in elderly patients. Limited clinical data are available to guide the reversal of warfarin or TSOAs in patients who are bleeding or need an urgent invasive procedure or operation. A panel of five experts with diverse backgrounds in anticoagulation therapy, cardiology, critical care, and emergency medicine and with experience in managing complications of anticoagulation therapy was convened to develop practical strategies for managing patients receiving oral anticoagulants who are bleeding or have an urgent need for an invasive procedure. The strategies were designed to guide clinicians in the acute care setting by providing efficient and potentially effective management concepts to avoid delays in initiating treatment that could adversely affect patient outcomes. The consensus of this expert panel is summarized herein. Recommendations are based on currently available evidence from a comprehensive review of the literature and other pertinent data, along with the experience and expert opinion of the panelists. CONCLUSION: Bleeding is a serious complication of the use of oral anticoagulants, and limited information is available to guide the reversal of warfarin or TSOAs in patients who are bleeding or are in need of an urgent invasive procedure. Use of a systematic approach to assessing and treating these patients based on available evidence and expert opinion can help avoid delays that could adversely affect patient outcomes.

The impact of pharmacist-directed patient education and anticoagulant care coordination on patient satisfaction.

BACKGROUND: Patient satisfaction data played a role in determining Medicare reimbursement as of October 2012. Clinical pharmacy services could improve satisfaction of hospital inpatients but it is unclear whether this relates to performance on standardized hospital surveys. OBJECTIVE: To describe the impact on patient satisfaction of patient education and follow-up care coordination provided by an inpatient pharmacist-directed anticoagulation service (PDAS). METHODS: This study was conducted at an urban, tertiary care hospital. PDAS is a clinical pharmacy service that has improved transition-of-care, safety, and efficacy involving anticoagulation at our institution. Patients receiving inpatient anticoagulation during February 2001-April 2007 (pre-PDAS) and December 2008-December 2010 (post-PDAS), who responded to a mail-in survey, were included. Survey items included satisfaction ("How satisfied were you with the medical care?"), amount of information ("Was the amount of information you received about your medicine...?"), clarity of information ("Was the clarity of the information about your medicine...?"), answer quality ("Were the answers to your questions about your medicine...?"), and spoke to a pharmacist ("Did a pharmacist speak with you during your stay?"). Response options for amount of information, clarity of information, answer quality, and satisfaction used a symmetric 5-point Likert-type scale, with options 1-5 indicating most to least positive, respectively. Options 1-2 were considered positive and options 3-5 were considered negative. Primary analysis compared patient satisfaction (defined as rate of positive responses) between pre-PDAS and post-PDAS respondents. χ² test was used for all comparisons. RESULTS: Surveys were distributed to 1694 patients after discharge, with 687 (40.6%) responding. Post-PDAS respondents had improved patient satisfaction for all positive response items, compared to pre-PDAS scores. Amount of information increased by 37.2%, clarity of information increased by 35.2%, answer quality increased by 29.5%, and satisfaction increased by 10.6% (p < 0.001 for all comparisons). CONCLUSIONS: Hospitals deploying focused programs with systematic approaches to patient-pharmacist communication may positively impact patient satisfaction.

Pharmacologic interventions for reversing the effects of oral anticoagulants.

PURPOSE: To describe the pharmacologic agents and strategies used for urgent reversal of warfarin and the target-specific oral anticoagulants dabigatran, rivaroxaban, and apixaban. SUMMARY: To reverse the anticoagulant effects of warfarin in patients who are bleeding or need surgery, exogenous vitamin K (phytonadione) may be used in combination with another, shorter-acting intervention, such as fresh frozen plasma (FFP), prothrombin complex concentrate (PCC), recombinant factor VIIa, or activated PCC (aPCC). Three-factor PCC contains factors II, IX, and X in an inactivated form, and four-factor PCC also includes factor VII in an inactivated form. No four-factor PCC products are available in the United States, but aPCC, which contains the same four factors with factor VII provided in an activated form, is available. The intervention depends on the International Normalized Ratio, presence of bleeding, and need for and timing of surgery. Research suggests that clotting factor concentrates are more effective than FFP alone for warfarin reversal. These products also may be useful for reversing the effects of target-specific oral anticoagulants, but limited efficacy and safety data are available to support their use. The risks and benefits associated with these products need to be weighed before their use for reversal of dabigatran, rivaroxaban, or apixaban. Additional clinical data are needed to clearly define the role of concentrated clotting factor products in reversal and to determine the optimal clotting factor concentrate product and dose for urgent reversal of oral anticoagulation. CONCLUSION: Phytonadione and clotting factor concentrates appear to have a role for reversal of warfarin, and limited evidence suggests that clotting factor concentrates could have a role in reversal of target-specific oral anticoagulants in an emergency situation.

Antithrombotic alternatives for stroke prevention in atrial fibrillation: critical differences and remaining questions.

Three therapeutic alternatives for prevention of stroke in patients with atrial fibrillation are available in dabigatran (an oral direct thrombin inhibitor), rivaroxaban, and apixaban (both oral blood coagulation factor Xa inhibitors). Compared with warfarin, these new agents have a more predictable pharmacodynamic response and fewer major clinically relevant drug-drug interactions. These agents also have few, if any, food-drug interactions, and infrequent or no need for routine laboratory monitoring. These agents also bring new disadvantages, particularly lack of clearly defined reversal strategies, inability to effectively monitor patient response, and higher cost. Selection of the most appropriate oral antithrombotic agent for a given patient is dependent on clinician knowledge of the similarities and critical differences between the available antithrombotic medications.