A Practical Guide to Understanding and Treating Peripheral Artery Disease.

ABSTRACT: Peripheral arterial disease (PAD) is the third leading cause of atherosclerotic morbidity after coronary heart disease and stroke yet is widely underdiagnosed and undertreated. Treatment of risk factors such as diabetes and cigarette smoking can benefit patients with PAD. Patients should have adequate blood pressure and lipid control to decrease clinical manifestations and symptoms of PAD. Use of antithrombotic medications should be individualized to the patient depending on the presence of symptoms, revascularization, and comorbidities. All patient care providers, including physicians, pharmacists, nurse practitioners, and physician assistants, should incorporate PAD screening in their at-risk patients to improve access for appropriate earlier diagnosis, initiation of guideline directed therapy, and risk factor modification to reduce both major adverse CV and limb outcomes. The purpose of this narrative review is to provide an overview of PAD and summarize clinical trial evidence and guideline recommendations for screening and treatment to increase awareness among health care providers to ultimately have a positive impact on patient care.

A systematic review of therapeutic enoxaparin dosing in obesity.

Enoxaparin is a hydrophilic drug with obesity having little effect on its apparent volume of distribution, therefore patients with obesity receiving standard 1 mg/kg dosing may be at a higher risk of supratherapeutic dosing. Conversely, dose reducing patients with obesity could place already at risk patients at higher risk of a thrombotic event. Data and recommendations are variable for the most appropriate weight-based dose of therapeutic enoxaparin in obese patients, particularly those a weight > 100 kg or a body mass index (BMI) ≥ 40 kg/m2. The purpose of this systematic review was to globally evaluate these data to surmise optimal dosing recommendations for patients with obesity. A systematic review of English language studies was conducted and identified articles via Pubmed, EMBASE, and the Cochrane Central Register of Controlled Trials (CENTRAL) searches. Studies were included if they reported therapeutic enoxaparin use in adult patients with a BMI ≥ 40 kg/m2 or body weight > 100 kg and the percentage of patients achieving a therapeutic anti-Xa based on a weight-based dose or the weight-based dose required to produce a therapeutic anti-Xa level. Therapeutic attainment of anti-Xa levels were assessed across enoxaparin weight-based dosing categories including a very low dose group: < 0.75 mg/kg, low dose group: 0.75-0.85 mg/kg, and standard dose group: ≥ 0.95 mg/kg. Rates of bleeding and thrombosis were also evaluated. A total of eight studies were included. For anti-Xa level assessment, 682 patients were included. A total of 62% of anti-Xa levels were therapeutic in the very low dose group, 66% in the low dose group, and 42% in the standard dose group. Overall rates of total bleeding and thrombosis were assessed in 798 patients. A total of 29 bleedings (3.6%) occurred, and 27 reported a relationship to dose. Most bleedings, 85.2% (n = 23/27), occurred with doses in the standard dose group (≥ 0.95 mg/kg). Thrombosis occurred in 5 patients (0.6%). Utilization of a reduced weight-based dosing strategy for therapeutic enoxaparin in obese patients may increase the percentage of patients with a therapeutic anti-Xa level.

A Retrospective Review of Cardiogenic Shock Development in Patients With ST-Elevation Myocardial Infarction and Percutaneous Coronary Intervention Receiving Early Beta-Blockers.

ABSTRACT: Beta-blockers (BBs) have proven to improve morbidity and mortality in patients after an ST elevation myocardial infarction (STEMI). Guidelines suggest initiating a BB within 24 hours, except in those with risk factors for developing cardiogenic shock, although published literature is conflicting regarding the true association of these risk factors with shock. This retrospective cohort study aimed to assess whether the presence of defined risk factors was associated with cardiogenic shock after early BB administration in patients with a STEMI and percutaneous coronary intervention. The primary outcome determined the rate of cardiogenic shock development and secondarily determined any characteristics associated with cardiogenic shock in patients who received beta blockers. The population included 299 patients and cardiogenic shock occurred in 8 patients (2.7%). There were no median (interquartile range) differences in age [63 years (60-71) versus 62 years (52-71); P = 0.4965], systolic blood pressure [110 mm Hg (105-115) versus 109 mm Hg (103-114); P = 0.6027], or heart rate [90 (78-104) versus 76 (64-90); P = 0.0697] before BB administration in patients who developed shock versus those who did not, respectively. Hours to BB administration from arrival [15.6 (6.0-54.8) versus 21.9 (10.6-42; P = 0.6968] and the number (%) with anterior infarction [3 (37.5%) versus 107 (36.8%); P = 1.000] were similar between groups. There was a statistically significant higher median (interquartile range) peak troponin [140 ng/mL (54-304) versus 49 ng/mL (16-132); P = 0.0354] in patients who developed shock. Early initiation of a BB in patients with STEMI and percutaneous coronary intervention with risk factors for cardiogenic shock does not seem to be associated with shock in most patients.

Early Versus Late Administration of P2Y 12 Inhibitors in Non-ST Segment Elevation Myocardial Infarction and Delayed Cardiac Catheterization.

ABSTRACT: Regardless of early invasive or ischemia-guided approaches to non-ST segment elevation myocardial infarction (NSTEMI) management, P2Y 12 inhibitors remain the backbone in therapy. The ideal timing of administration remains unclear. The purpose of this study was to determine the safety and effectiveness of early versus late administration of P2Y 12 inhibitors in patients presenting with an NSTEMI who go to the catheterization laboratory beyond 24 hours from presentation. We performed a single center, retrospective cohort study. Patients were classified into groups depending on whether they received early versus late administration of a P2Y 12 inhibitor. The primary outcome was the rate of major and clinically relevant, nonmajor bleeding (CRNMB). Secondary outcomes included troponin peak and length of stay after cardiac catheterization. Of the 121 patients included, 53 patients were in the early and 68 patients were in the late group. The number of bleeding events were similar between both groups ( P = 1.00). There were 3 (5.7%) major bleeding events in the early group and 5 (7.4%) bleeding events in the late group. There were 5 (9.4%) CRNMB events in the early group and 6 (8.8%) CRNMB events in the late group. There was a significant difference in troponin peak, 4.56 ng/mL in the early group and 1.77 ng/mL in the late group ( P = 0.02). The rate of bleeding did not differ between patients who received early or late administration of P2Y 12 inhibitors for NSTEMI management who undergo delayed cardiac catheterization.

Comparison of Ischemic and Bleeding Events Between Short-Duration Versus Long-Duration Tirofiban Regimens in Patients With ST-Segment Elevation Myocardial Infarction Undergoing Percutaneous Coronary Intervention.

ABSTRACT: Tirofiban has been used historically as a bridge to platelet inhibition with clopidogrel in ST-segment myocardial infarction (STEMI) during percutaneous coronary intervention (PCI) to prevent stent thrombosis. However, ticagrelor and prasugrel reach similar levels of platelet inhibition at 30 minutes to that of clopidogrel at 6 hours, challenging the need for long-duration tirofiban. This 1-year, retrospective cohort study compared ischemic and bleeding outcomes of short-duration versus long-duration tirofiban regimens in patients with STEMI who received ticagrelor or prasugrel at the time of PCI. The primary outcome was major adverse cardiovascular events (MACEs) including cardiovascular mortality, recurrent myocardial infarction, urgent target vessel revascularization, or stroke. Secondary outcomes included individual MACE, all-cause mortality, bleeding events defined by the International Society on Thrombosis and Hemostasis, thirty-day readmissions for MACE and bleeding, and tirofiban pharmacy cost. A total of 283 charts were reviewed and 177 included (short duration n = 57; long duration n = 120). MACE rates were similar between short-duration and long-duration groups (0 [0%] vs. 5 [4.2%]; P = 0.18), including 4 cardiovascular deaths and 1 recurrent myocardial infarction. Bleeding event rates were also similar in short-duration versus long-duration groups including major bleeds (2 [3.5%] vs. 2 [1.7%]; P = 0.60) and clinically relevant nonmajor bleeds (3 [5.3%] vs. 9 [7.5%]; P = 0.75). Cost analysis indicated lower pharmacy cost with the short-duration group. In this cohort of patients with STEMI receiving a fast-acting P2Y12 inhibitor, the length of tirofiban infusion did not affect ischemic or bleeding outcomes, yet short-duration regimens were lower cost.

Comparison of Bleeding Rates between Oral Anticoagulants in Combination with Dual Antiplatelet Therapy (Triple Therapy) in a Real-World Cohort.

Background: Triple antithrombotic therapy including an anticoagulant, P2Y12 inhibitor, and aspirin increases bleed risk up to 27%. The components of this regimen can vary, which may impact bleed risk. Objective: To compare the safety of various triple antithrombotic regimens. Methods: An Institutional Review Board approved retrospective cohort study was conducted from 2014 to 2017. Patients admitted to a large urban health system on triple therapy were evaluated for inclusion. The primary outcome compared rates of International Society of Thrombosis and Hemostasis major and clinically relevant nonmajor bleeding during index admission or within 90 days in patients receiving warfarin, rivaroxaban, or apixaban; aspirin; and a P2Y12 inhibitor. A multivariable logistic regression assessed the association between bleeding, antithrombotic use, and relevant confounding variables. Results: Three hundred and seventy-two patients were included: 238 patients received warfarin, 63 received rivaroxaban, and 71 received apixaban. Forty-five patients (12.1%) experienced a bleed, 25 of which (55.6%) were major. The rate of bleeding was 12.2% (n = 29) with warfarin, 14.3% (n = 9) with rivaroxaban, and 9.9% (n = 7) with apixaban (P = .7335). The use of prasugrel versus clopidogrel (OR 4.35, 95% CI 1.20-15.72; P = .025) and admission hemoglobin less than 12 mg/dL (OR 2.54, 95% CI 1.28-5.04; P = .008) were identified as risk factors associated with bleeding in the model. Conclusion: In patients on triple antithrombotic therapy, choice of oral anticoagulant did not impact bleeding rates, but use of prasugrel and a low baseline hemoglobin were associated with increased bleed rates which warrants further investigation.

Comparison of Higher-Than-Standard to D-Dimer Driven Thromboprophylaxis in Hospitalized Patients With COVID-19.

Introduction: Coronavirus disease 2019 is a global health threat often accompanied with coagulopathy. Despite use of thromboprophylaxis in this population, thrombotic event rates are high. Materials and methods: This was a multicenter, retrospective cohort study comparing the safety and effectiveness of thromboprophylaxis strategies at 2 institutions in hospitalized patients with coronavirus disease 2019. Regimen A utilized a higher-than-standard thromboprophylaxis dosage and Regimen B received full-dose anticoagulation for any D-dimer 3 mcg/mL or greater and prophylactic for less than 3 mcg/mL. The primary outcome compared the rate of thrombotic events between treatment groups. Secondary endpoints compared rates of major or clinically relevant non-major bleeding as well as the proportion of patients in each group experiencing thrombotic events within 30 days of discharge. Results: One-hundred fifty-three patients were included in the analysis, 64 receiving Regimen A and 89 receiving Regimen B. Seven (4.6%) thrombotic events occurred, 3 (4.7%) in patients receiving Regimen A, and 4 (4.5%) in Regimen B (P = 1.0). Twelve patients (13.5%) receiving Regimen B had a bleeding event versus 2 (3.1%) in Regimen A (P = .04), half of which were major in each group. All patients who bled in either treatment group were receiving mechanical ventilation, and 12 of 14 were receiving full-dose anticoagulation. One patient receiving Regimen A was readmitted with a pulmonary embolism. Conclusions: In this study, the thromboprophylactic regimen impacted bleeding, but no significant difference was seen with thrombotic outcomes. Almost all patients who experienced a bleed were mechanically ventilated and receiving full-dose anticoagulation. The use of full-dose anticoagulation should be cautioned in this population without an additional indication.

Inpatient Initiation of Sacubitril/Valsartan.

OBJECTIVE: Discuss the literature and describe strategies to overcome barriers of inpatient initiation of sacubitril/valsartan in patients with heart failure with reduced ejection fraction (HFrEF). DATA SOURCES: A PubMed, EMBASE, and Google Scholar literature search (January 2014 to June 2020) limited to English language articles was conducted with the following terms: sacubitril/valsartan, initiation, inpatient, hospitalized, B-type natriuretic peptide (BNP), N-terminal pro-B-type natriuretic peptide (NT-proBNP), diuretic, cost, and cost-effectiveness. STUDY SELECTION AND DATA EXTRACTION: Included articles described inpatient initiation of sacubitril/valsartan or described its impact on BNP, NT-proBNP, diuretic dosing, or cost of care. DATA SYNTHESIS: A total of 20 studies were identified based on included search terms. CONCLUSIONS: Sacubitril/valsartan should be considered for hemodynamically stable patients with HFrEF (New York Heart Association class II or III), potassium <5.2 mmol/L, without a history of angioedema, and after a 36-hour washout from angiotensin-converting enzyme (ACE) inhibitor or aliskiren, if applicable. An appropriate dose can be determined based on the patient's previous ACE inhibitor or angiotensin receptor blocker dose and/or blood pressure along with patient-specific factors. To overcome barriers of use, the following are recommended: NT-proBNP or BNP with establishment of a new baseline 1 month after initiation may be used for prognosis or diagnosis; careful monitoring of diuretic requirements; utilization of multiple strategies to overcome cost barriers; and use of interdisciplinary care.

Evaluation of metoprolol versus diltiazem for rate control of atrial fibrillation in the emergency department.

OBJECTIVE: The purpose of this study was to compare the effectiveness and safety of the metoprolol and diltiazem administration in the Emergency Department (ED) for rate control of supraventricular tachycardia. METHODS: This was a retrospective cohort study of adult patients who presented to the ED with ventricular rates ≥120 beats per minute (bpm) and who received bolus doses of either intravenous metoprolol or intravenous diltiazem. The primary outcome was achievement of rate control, defined as heart rate < 110 bpm, at two hours after administration of the last bolus dose of metoprolol or diltiazem. Safety outcomes included occurrence of hypotension, defined as systolic blood pressure < 90 mmHg or diastolic blood pressure < 60 mmHg, and bradycardia, defined as heart rate < 60 bpm. RESULTS: There were 166 patients receiving metoprolol and 183 patients receiving diltiazem included in the study. The primary outcome, rate control at two hours after the last bolus dose of metoprolol or diltiazem was similar between the two groups (45.8% vs 42.6%, p = 0.590, respectively). The percentage of patients achieving rate control was also similar (47.0% vs 41.6%, p = 0.333) at one hour. At 0.5 h HR had a significantly greater numerical (diltiazem: 29.3 ± 23.1 bpm vs metoprolol: 21.8 ± 18.9 bpm, p = 0.012) and percent decrease (21.1% vs 15.94%, p = 0.014) in the diltiazem group compared to metoprolol. There was no significant difference in occurrence of bradycardia in the two groups (diltiazem: 3.83% vs metoprolol: 1.2%, p = 0.179). More patients in the diltiazem group compared to the metoprolol group experienced hypotension (39.3% vs 23.5%, p = 0.002). The difference in systolic hypotension events was not significantly different (9.29% vs 5.42%, p = 0.221), while the difference in diastolic hypotension events was significantly different (37.7% vs 22.3%, p = 0.002). CONCLUSION: There was no difference in acute rate control effectiveness two hours after the last bolus dose of diltiazem and metoprolol for supraventricular tachycardias. There was a significantly higher occurrence of hypotension in the diltiazem group which was driven by higher rates of diastolic blood pressures less than 60 mmHg.

NAPLEX Preparatory Perceptions from Recent Graduates at One College of Pharmacy.

OBJECTIVES: The current study assessed how students prepared for the North American Pharmacist Licensure Examination (NAPLEX), and examined factors associated with first-time pass rates. In addition, updated information on student perceptions of several currently available NAPLEX preparation resources was collected. METHODS: A survey was administered to 2022 graduates from 1 school, which collected data on student demographics, and NAPLEX-related items regarding when the exam was taken and how students prepared, including resources used. The association between first-time success (pass, no pass) and grade point average (GPA), timing of test date after graduation, effort toward exam, and number of hours studied was examined. In addition, student ratings of NAPLEX preparation resources in terms of usefulness, representativeness to actual examination, and monetary value were reported. RESULTS: A total of 52 individuals completed the survey. Pharmacy GPA over 3.5, taking the NAPLEX within 60 days of graduation, and exerting moderate to extensive effort to pass the NAPLEX were all associated with higher first-time pass rates. All students reported using at least 1 RxPrep resource, which students rated highly and suggested the school provide as a resource for NAPLEX preparation. CONCLUSION: This study found that taking the NAPLEX examination within 60 days of graduation, contributing moderate to extensive effort to pass the examination, as well as a cumulative GPA of 3.5 (out of 4) or above were related to success on the NAPLEX. Additionally, students reported high satisfaction with RxPrep resources.

Effect of P2Y12 platelet reactivity level on peri- and postoperative outcomes of cardiac surgery patients.

BACKGROUND: Evidence surrounding P2Y12 platelet reactivity units (PRU) impact on bleeding outcomes in patients undergoing coronary artery bypass is varied. This study sought to assess whether on-pump CABG procedures result in increased bleeding in patients with high compared to low PRUs. METHODS: This retrospective cohort study compared those with a PRU level ≤237 (low PRU group) to >237 (high PRU group). The primary outcome assessed massive or severe bleeding in accordance with universal definition of perioperative bleeding criteria. Secondary outcomes assessed mortality, length of stay and relevant bleeding related outcomes (e.g., rates of moderate or lower classifications of bleeding, chest tube output, blood product receipt). RESULTS: A total of 69 patients were included, 47 in the low and 22 in the high PRU groups. Patients were a median (IQR) 66 (62-74) years and 84.1% (N.=58) were male. Most patients received clopidogrel prior to procedure (39 [83%] in low and 18 [81.8%] in high PRU group; P=1.0000). The rate of the primary outcome was 14.9% (N.=7) in patients with a low PRU and 18.2% (N.=4) in patients with a high PRU; P=0.7345. The rate of moderate bleeding was 59.6% (N.=28) in the low and 27.3% (N.=6) in the high PRU group (P=0.0124). Packed red blood cells (PRBCs) were administered to more patients in the low (23 [48.9%]) than the high PRU group (2 [22.7%]; P=0.0388). There were no differences in other blood product requirement, chest tube output, factor products administered, mortality, or length of stay. CONCLUSIONS: This study determined that low preoperative P2Y12 PRU levels may influence moderate bleeding in patients undergoing cardiac surgery, but not massive or severe bleeding.

Implementation and Evaluation of a Residency Preparation Program for Fourth-Year Doctor of Pharmacy Students.

OBJECTIVE: To describe the impact of a formal residency preparation program on student match rates, and to evaluate student-reported advisement activities and perceptions of the residency application process. METHODS: An optional, noncredit-bearing, residency preparation program was implemented in professional year 4 (PY4) of the Doctor of Pharmacy curriculum. The program consisted of 4 residency preparation presentations and/or workshops: curriculum vitae writing, navigating the residency application process and American Society of Health-Systems Pharmacy Midyear Clinical Meeting, letter of intent writing, and interview skills. Students attended either virtually or in person, with 3 of the 4 sessions including small group breakout sessions. The program also included dedicated, 1-on-1 residency advisement with residency-experienced advisors. RESULTS: Residency match rates following program implementation increased from 74.3% (comparison group) to 87.5% (intervention group). More students in the intervention group reported that their advisor assisted them with curriculum vitae review, letter of intent review, and interview skills. In addition, the intervention group reported significantly more time spent meeting with their advisor during PY4 than the comparison group. Students found the program to be beneficial to their professional development, indicated that it helped them to obtain a residency position, and expressed that they would participate in the residency preparation program again. CONCLUSION: Implementation of a formal residency preparation program for PY4 students that included 1-on-1 dedicated residency advisement increased match rates and interaction between students and their residency advisor.

Comparison of bleeding and ischemic events with apixaban vs. rivaroxaban in triple antithrombotic therapy regimens.

OBJECTIVE: To compare the risk of readmissions for major bleeding within one year between apixaban and rivaroxaban as a component of triple antithrombotic therapy. METHODS: This study was a multicenter, retrospective cohort study conducted at two academic medical centers in the Western New York and New York City region between July 1, 2011 and September 25, 2019. Adult patients were included if they were diagnosed with atrial fibrillation or venous thromboembolism and discharged on new triple antithrombotic therapy. The primary outcome compared the rates of 1-year readmission for major bleeding between apixaban and rivaroxaban groups. Secondary outcomes included rate of ischemic outcomes. Time to event analysis was determined with a Kaplan-Meier plot and Cox proportional hazard ratios (HR). RESULTS: A total of 378 patients were included in the study, 212 in the apixaban group and 166 in the rivaroxaban group. Within 1 year, readmission for major bleeding events occurred in six (2.8%) patients in the apixaban group and four (2.4%) patients in the rivaroxaban group ( P  = 1.000). After adjustment, the major bleeding event rate was not statistically significantly different between apixaban and rivaroxaban [adjusted hazard ratio (aHR) 0.68, 95% confidence interval (CI) 0.12-3.77; P  = 0.6624]. Higher albumin levels were identified to be protective against major bleeding related readmission events (aHR 0.18, 95% CI 0.05-0.63; P  = 0.0072). The ischemic outcome occurred in seven (3.3%) patients in the apixaban group and three (1.8%) in the rivaroxaban group ( P  = 0.7368). CONCLUSION: Use of apixaban or rivaroxaban in a triple antithrombotic regimen was not associated with bleeding or ischemic outcomes.

Impact of a pharmacist collaborative drug therapy management protocol on utilization of a discharge prescription program and hospital readmissions.

PURPOSE: To evaluate the impact of a collaborative drug therapy management (CDTM) agreement allowing a pharmacist to automatically prescribe refills of discharge medications to patients' preferred outpatient pharmacy on utilization of a hospital discharge prescription program and hospital readmission rates. METHODS: This was a single-center, quasi-experimental pre-post intervention study. Patients aged 18 years or older discharged from the cardiology services to home were eligible for inclusion in the study. The CDTM agreement was initiated on July 1, 2019. Patients discharged to home from July 1, 2018, to June 30, 2019, were assigned to the historical control group. The primary outcome was the difference in the proportion of patients who used the bedside medication delivery service at hospital discharge between the groups. Secondary outcomes included 30-day hospital readmissions and a descriptive analysis of medications prescribed by a pharmacist through the program. A χ2 test was used to assess the primary outcome, and multivariable logistic regression was used to assess hospital readmissions. RESULTS: In total, 1,704 and 2,200 patients were discharged in the control and CDTM groups, respectively. The CDTM group had a greater proportion of patients who participated in the discharge prescription program compared to the historical control group (77.8% vs 68.7%; P < 0.0001). There was no difference in 30-day hospital readmission rate between the groups (adjusted odds ratio, 1.01; 95% confidence interval, 0.83-1.23; P = 0.94). CONCLUSION: A CDTM protocol to improve the availability of medication refills at a patient's regular outpatient pharmacy improved utilization of a bedside medication delivery service but did not change 30-day readmission rates.

Retrospective Study of Appropriate Primary Prevention in Postmenopausal Women Presenting with a Major Adverse Cardiovascular Endpoint (MACE).

BACKGROUND: Postmenopausal women may be at an increased risk for cardiovascular events. The postmenopausal transition represents a key time for implementation of preventative strategies to reduce the risk of cardiovascular disease. The objective of this study was to evaluate the appropriate use of primary prophylaxis of cardiovascular disease in this population and to determine if an opportunity exists for improvement in primary prevention prescribing. METHODS: A single-center, retrospective study was conducted of postmenopausal women aged 45-60 years between 1 October 2019 and 30 April 2021 with a diagnosis of a new major adverse cardiovascular event (MACE). This study was approved by the University at Buffalo Institutional Review Board. RESULTS: After application of inclusion and exclusion criteria, 231 patients were included and analyzed. Median age was 55 years; 66.6% white; median body mass index was 30.11 kg/m2; 30.3% history of diabetes; 51.1% current smokers; 82.3% with a primary care provider (PCP); 97.6% insured. Patients with diabetes, current smokers, and those without a PCP were more likely to have inappropriate primary prevention use than patients without diabetes, non-smokers, and with a PCP, respectively (78.7% vs. 51.3%, p = 0.0002; 57.6% vs. 42.4%, p = 0.0177; 73.7% vs. 56.0%, p = 0.0474). Specifically, current smokers, and those with diabetes had significantly more inappropriate use of aspirin and statins for primary prevention than non-smokers and patients without diabetes. CONCLUSIONS: This study observed the use of appropriate primary prevention therapies in postmenopausal women and found that an opportunity may exist to improve prescribing appropriate primary prevention therapies for certain groups, most notably in postmenopausal women with diabetes, smokers, uninsured, and those without a PCP.

Combination Therapy of Ezetimibe and Rosuvastatin for Dyslipidemia: Current Insights.

Cardiovascular disease is one of the leading causes of death around the world with various efforts being made to reduce risk in patients through preventive measures. One major method for prevention has been managing cholesterol, particularly low-density lipoprotein to decrease atherosclerotic plaque burden, potentially decreasing future cardiac complications. Statins have been the gold standard therapy for hypercholesterolemia treatment due to their ease of dosing, limited drug interactions, and favorable safety profile. Unfortunately, statin therapy alone is not always effective enough to adequately control a patient's elevated lipid levels and combination therapy may be warranted. Ezetimibe is commonly added to regimens to help augment cholesterol lowering by inhibiting the absorption of cholesterol. The recent approval of a combination tablet of high-intensity rosuvastatin and ezetimibe has introduced a potentially more beneficial option for cholesterol management in addition to the only available combination of moderate intensity simvastatin and ezetimibe. We aimed to identify potential beneficial effects of ezetimibe by comparing its use in combination with high-intensity rosuvastatin compared to a statin therapy alone or in combination with moderate intensity simvastatin through a literature review. The current evidence indicated that combination therapy outperformed statin monotherapy in reduction of low-density lipoprotein cholesterol and patients were more likely to achieve their target low-density lipoprotein cholesterol goal level. This suggests rosuvastatin/ezetimibe combination holds a potential place in therapy for patients requiring a more aggressive reduction in cholesterol to help prevent atherosclerotic disease.

Implementation and Assessment of a Heart Failure Virtual Patient Simulation in a Required Pharmacotherapy Course.

Objective. To assess second year Doctor of Pharmacy students' academic performance in and perceptions of a heart failure (HF) virtual patient simulation used in a required pharmacotherapy course.Methods. A heart failure virtual patient simulation was created to augment heart failure pharmacotherapy course material at the University at Buffalo School of Pharmacy and Pharmaceutical Sciences in the fall of 2019. This was a retrospective, pre-post observational cohort study. The primary objective was to compare student performance on heart failure pharmacotherapy examination questions in a cohort of students who completed a virtual patient simulation in 2019 compared to a control cohort who completed a paper-based case activity in 2018. Student perceptions of the simulation experience were assessed via electronic survey.Results. Students completed either the virtual patient simulation (n=122) or a paper-based case activity (n=123). Overall, the proportion of correctly answered heart failure pharmacotherapy examination questions was 83.3% in the virtual simulation group compared to 79.2% in the paper-based case group. Survey results indicated that students would prefer that the virtual patient simulation be incorporated in the pharmacotherapy curriculum.Conclusion. Use of a heart failure virtual patient simulation was associated with improved examination performance and was well received by students.

Neural Net Modeling of Checkpoint Inhibitor Related Myocarditis and Steroid Response.

Background: Serious but rare side effects associated with immunotherapy pose a difficult problem for regulators and practitioners. Immune checkpoint inhibitors (ICIs) have come into widespread use in oncology in recent years and are associated with rare cardiotoxicity, including potentially fatal myocarditis. To date, no comprehensive model of myocarditis progression and outcomes integrating time-series based laboratory and clinical signals has been constructed. In this paper, we describe a time-series neural net (NN) model of ICI-related myocarditis derived using supervised machine learning. Methods: We extracted and modeled data from electronic medical records of ICI-treated patients who had an elevation in their troponin. All data collection was performed using an electronic case report form, with approximately 300 variables collected on as many occasions as available, yielding 6000 data elements per patient over their clinical course. Key variables were scored 0-5 and sequential assessments were used to construct the model. The NN model was developed in MatLab and applied to analyze the time course and outcomes of treatments. Results: We identified 23 patients who had troponin elevations related to their ICI therapy, 15 of whom had ICI-related myocarditis, while the remaining 8 patients on ICIs had other causes for troponin elevation, such as myocardial infarction. Our model showed that troponin was the most predictive biomarker of myocarditis, in line with prior studies. Our model also identified early and aggressive use of steroid treatment as a major determinant of survival for cases of grade 3 or 4 ICI-related myocarditis. Conclusion: Our study shows that a supervised learning NN can be used to model rare events such as ICI-related myocarditis and thus provide clinical insight into drivers of progression and treatment outcomes. These findings direct attention to early detection biomarkers and clinical symptoms as the best means of implementing early and potentially life-saving steroid treatment.

Clinical characteristics, time course, treatment and outcomes of patients with immune checkpoint inhibitor-associated myocarditis.

BACKGROUND: Immune checkpoint inhibitors (ICI) have emerged as a front-line therapy for a variety of solid tumors. With the widespread use of these agents, immune-associated toxicities are increasingly being recognized, including fatal myocarditis. There are limited data on the outcomes and prognostic utility of biomarkers associated with ICI-associated myocarditis. Our objective was to examine the associations between clinical biomarkers of cardiomyocyte damage and mortality in patients with cancer treated with ICIs. METHODS: We retrospectively studied 23 patients who developed symptomatic and asymptomatic troponin elevations while receiving ICI therapy at a National Cancer Institute-designated comprehensive cancer center. We obtained serial ECGs, troponin I, and creatine kinase-MD (CK-MB), in addition to other conventional clinical biomarkers, and compared covariates between survivors and non-survivors. RESULTS: Among patients with myocarditis, higher troponin I (p=0.037) and CK-MB (p=0.034) levels on presentation correlated with progression to severe myocarditis. Higher troponin I (p=0.016), CK (p=0.013), and CK-MB (p=0.034) levels were associated with increased mortality, while the presence of advanced atrioventricular block on presentation (p=0.088) trended toward increased mortality. Weekly troponin monitoring lead to earlier hospitalization for potential myocarditis (p=0.022) and was associated with decreased time to steroid initiation (p=0.053) and improved outcomes. CONCLUSIONS: Routine troponin surveillance may be helpful in predicting mortality in ICI-treated patients with cancer in the early phase of ICI therapy initiation. Early detection of troponin elevation is associated with earlier intervention and improved outcomes in ICI-associated myocarditis. The recommended assessment and diagnostic studies guiding treatment decisions are presented.