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The American Society of Hematology and American College of Chest Physicians heparin-induced thrombocytopenia guidelines recommend calculation of a pretest probability score prior to performing laboratory testing, and the 4Ts score is commonly used. Inter-rater agreement of the 4Ts score has been evaluated, but limited data are available regarding the reliability of the 4Ts score when performed by nonexpert clinicians. The purpose of this study was to Compare 4Ts scores calculated by medical teams to an expert. A single-center observational study was conducted in patients evaluated for heparin-induced thrombocytopenia over 24 months. The primary outcome was difference in mean 4Ts score calculated by the medical team compared with an expert. Secondary outcomes included inter-rater agreement in risk category assignment and the negative predictive value (NPV) of the 4Ts score. The mean total 4Ts score was significantly higher when calculated by the medical team compared with expert (4.16 ± 1.41 versus 3.42 ± 1.53; P < 0.001). There was slight agreement in risk category assignment (Cohen κ coefficient = 0.164; P = 0.005). The NPV of the 4Ts score was 0.949 (95% confidence interval 0.891-1.000) when calculated by the medical team and 0.927 (95% confidence interval 0.869-0.984) when calculated by expert. Total 4Ts scores calculated by the medical team were significantly higher with only slight inter-rater agreement compared with expert. The NPV of the 4Ts score when calculated by nonexperts may be lower than previously reported. The recommendation to forgo laboratory testing for low 4Ts score patients may need to be revisited.

Pulmonary embolism (PE) is a significant contributor to morbidity and mortality in the United States. Catheter-directed, ultrasound-assisted thrombolysis (USAT) uses high-frequency, low-energy ultrasound waves to disaggregate uncrosslinked fibrin fibers and increase thrombus penetration of a locally delivered thrombolytic to treat an acute PE. The purpose of this study is to compare the efficacy and safety of catheter-directed USAT versus systemic anticoagulation alone in submassive PE. This was a single-center, retrospective study of patients with a diagnosis of acute submassive PE from April 4, 2014 to May 1, 2019 at a large, academic medical center. Subjects were split into two different groups based on treatment with either USAT with systemic anticoagulation or systemic anticoagulation alone. The primary outcome was the incidence of severe or life-threatening GUSTO bleeding within 72 h or until hospital discharge if sooner. A total of 130 subjects were included (n = 40 in the USAT group and n = 90 in systemic anticoagulation alone group). Significantly fewer subjects in the USAT group had an active diagnosis of cancer at the time of presentation (7.5% vs 28.9%, p = 0.006). There was no difference in severe or life-threatening GUSTO bleeding or any component of the GUSTO bleeding definitions. Administration of USAT with systemic anticoagulation was well-tolerated when compared to systemic anticoagulation alone, but bias may have led to selection of patients for USAT with a lower bleeding risk and higher functional status at baseline.

Cardiovascular disease is the leading cause of death globally, and deaths due to coronary heart disease or stroke account for over half of all cardiovascular deaths in the United States. While many important advances have been made in the treatment and secondary prevention of atherosclerotic cardiovascular disease (ASCVD), morbidity and mortality remain high. Aspirin has been commonly used for the primary and secondary prevention of ASCVD for decades and is an easily accessible therapeutic option. While it is a cornerstone of secondary prevention, its role in primary prevention is less clear and professional guidelines have differed in their recommendations. As literature has substantially evolved over the past 40 years, so too has our understanding of aspirin's role in the primary prevention of ASCVD. This article reviews landmark clinical trials of aspirin in primary prevention and highlights key changes in dosing strategies and demographics.

Background Loperamide is a widely available oral μ-opioid receptor agonist, and loperamide abuse is increasing by those seeking intoxication. Loperamide has potent QTc-prolonging properties, placing patients at risk for ventricular arrhythmias and sudden cardiac death. Case summary A 23-year-old woman was found to be in pulseless ventricular fibrillation with a QTc of 554 ms and received multiple defibrillations and IV lidocaine. Her toxicology studies were negative. She subsequently experienced multiple episodes of torsades de pointes and was found to be in cardiogenic shock with a left ventricular ejection fraction of 5%. Following multiple defibrillations, an Impella® mechanical circulatory support device was placed, and she was given IV magnesium and IV lidocaine. After mechanical circulatory support was withdrawn, she experienced major bleeding and was found to have a deep vein thrombosis, bilateral radial artery thrombosis, and multiple pulmonary embolisms in the setting of heparin-induced thrombocytopenia. After stabilizing, she admitted to taking 80 tablets of loperamide 2 mg in pursuit of euphoria. Discussion Loperamide is an increasingly popular agent of abuse. Loperamide-associated ventricular arrhythmias are rare with normal doses but more common with high doses, chronic ingestion, or interacting medications. Loperamide cardiotoxicity may be prolonged due to a long half-life and accumulation. Loperamide abuse may be under-recognized, leading to delays in treatment. Intravenous fluids, magnesium supplementation, chronotropes, transcutaneous or transvenous pacing, and defibrillation may be helpful in mitigating loperamide-associated polymorphic ventricular tachycardia. Clinicians should monitor for drug interactions in patients taking loperamide and screen for electrocardiographic abnormalities in those taking chronic or high-dose loperamide.

Purpose To evaluate the frequency and clinical impact of switches in antiplatelet therapy following implementation of CYP2C19 genotyping after percutaneous coronary intervention (PCI). Methods The frequency of escalation (clopidogrel switched to prasugrel/ticagrelor) and de-escalation (prasugrel/ticagrelor switched to clopidogrel) was evaluated in 1063 PCI patients who underwent CYP2C19 genotyping. Risk of major adverse cardiovascular or cerebrovascular (MACCE) and bleeding events over one-year was evaluated. Results Antiplatelet therapy switches were common (19%), with escalation (101/115: 88%) and de-escalation (77/84: 92%) occurring predominantly in patients with and without a CYP2C19 nonfunctional allele, respectively. Nonfunctional allele carriers initiated and continued on clopidogrel had a significantly higher risk of experiencing either a MACCE or bleeding event compared to those escalated to prasugrel/ticagrelor (52 vs. 19 events/100 patient-years; adjusted hazard ratio [HR] 2.89 [1.44–6.13], p=0.003). Patients without a nonfunctional allele de-escalated to clopidogrel had no difference in risk compared to those initiated and continued on prasugrel/ticagrelor (21 vs. 19 events/100 patient-years; adjusted HR 1.13 [0.51–2.34], p=0.751). Conclusions CYP2C19-guided escalation and de-escalation is common in a real-world setting. Continuation of clopidogrel in nonfunctional allele carriers is associated with adverse outcomes. De-escalation to clopidogrel in patients without a nonfunctional allele appears safe and warrants prospective study.

Purpose Clinical pharmacist productivity assessment has long been challenging, as a standard definition does not exist. A multistep project was undertaken with the intent to develop, validate, and implement an acute care clinical pharmacist productivity model. The initial step of the project was designed to identify, define, prioritize, and weight a comprehensive list of daily pharmacist responsibilities stratified by relative time spent on each function via consensus. Methods Delphi methodology applied by a panel of experts was used to identify a comprehensive list of acute care pharmacist responsibilities ranked in order of time intensity. Twenty-three acute care clinical pharmacists participated in the process. The consensus list was validated by time observation studies. Each responsibility was assigned a weight and corresponding work outputs by a consensus panel. Weighting of each responsibility was assigned according to the relative time intensity and complexity of each task. Results The results of the Delphi consensus process included the top 20 time-intensive responsibilities identified by the acute care clinical pharmacists. Timed observations of acute care clinical pharmacists yielded results similar to those of the consensus process. Selection of corresponding work outputs and weights for each responsibility provided the final requirements for the productivity model. Conclusion The development of an acute care clinical pharmacist productivity model first requires the selection of appropriate work outputs and weighting. The consensus process provided a newly identified comprehensive list of pharmacist responsibilities that will serve as the foundation of the clinical productivity model. Validated consensus methodology can be useful for engaging clinical pharmacists in decision-making and the development of a clinical productivity model.

Purpose The purpose of the project described here was to use the work outputs identified in part 1 of a 2-part research initiative to build and validate an acute care clinical pharmacist productivity model. Methods Following the identification of work outputs in part 1 of the project, relative weighting was assigned to all outputs based on the time intensity and complexity of each task. The number of pharmacists verifying an inpatient medication order each day was selected to represent the labor input. A multivariable linear regression was performed to determine the final work outputs for inclusion in the model. Productivity and productivity index values were calculated for each day from July 1, 2018, through June 30, 2019. Results Of the 27 work outputs identified via consensus by the clinical pharmacist working team, 17 work outputs were ultimately included in the productivity model. The average productivity during the period July 2018 through June 2019 was derived from the model and will serve as the baseline productivity for acute care clinical pharmacists. Conclusion Validated consensus methodology can be useful for engaging clinical pharmacist in decision-making and developing a clinical productivity model. When thoughtfully designed, the model can replace obsolete measures of productivity that do not account for the responsibilities of clinical pharmacists.

Purpose Heparin-induced thrombocytopenia (HIT) is a serious complication of heparin administration. Management strategies are complex and include discontinuing heparin products, initiating alternative anticoagulants, interpreting laboratory test results, documenting heparin allergies, and providing patient education. Medication error reports and a retrospective review conducted at an academic medical center revealed an opportunity for a quality improvement initiative and led to the creation of a multidisciplinary workflow for the management of HIT. In a pre-post study, the impact of the multidisciplinary workflow on the safety and management of HIT was evaluated. Methods The preimplementation group consisted of adult patients tested for suspected HIT from April 4, 2014, through May 31, 2016; the postimplementation group consisted of adult patients tested from November 1, 2016, through October 31, 2018. The primary outcome was the incidence of heparin product administration while HIT testing was ongoing. The secondary outcome was the rate of appropriate heparin allergy documentation. Results The incidence of heparin product administration while HIT testing results were pending was significantly reduced, from 54.2% to 20.0% (P < 0.001), after workflow implementation. The rate of appropriate heparin allergy documentation significantly increased, from 95.0% to 100% (P < 0.001). Conclusion Implementation of a multidisciplinary workflow for the management of HIT significantly reduced the incidence of heparin administration while testing was ongoing and improved the rate of appropriate heparin allergy documentation.

OBJECTIVES Problems related to medication use portend poor outcomes, but resources for expanding clinical pharmacy services are limited. We conducted a pilot study in the area of cardiology to determine the impact and feasibility of a trainee-integrated pharmacy practice (TIPP) model comprised of pharmacy residents and a clinical pharmacist. METHODS Coverage of 2 acute care and 1 intensive care team was distributed among 1 clinical pharmacist and 3 pharmacy residents. Patient care services included interdisciplinary rounds, order verification, medication reconciliation, counseling, clinical monitoring, and documentation. A pharmacy technician collected medication histories for newly admitted patients. Data related to medication reconciliation, clinical interventions, and time requirements were collected. Clinical services were compared to historical controls where data were available. RESULTS Over the 18-day pilot study, the mean daily census consisted of 33.4 ± 5.3 patients. Admission medication reconciliation was performed on 8.1 patients per day, resulting in the discovery of 3.5 discrepancies per patient. Of 18 patients receiving anticoagulant therapy, 9 were counseled prior to discharge. Compared to historical controls, the number of patients receiving medication reconciliation and discharge counseling improved by 81% and 70%, respectively (both P < .05). A total of 763 clinical interventions were recommended (42.4 per day), with many recognized in peer-reviewed literature as conferring improvements in clinical outcomes. Members of the model were active for a mean of 10-12 hours each day, with 6.3-7.2 hours corresponding to direct patient care. LIMITATIONS This was a single-arm, observational pilot study. CONCLUSION Implementation of a TIPP model significantly expanded clinical pharmacy services on an acute care cardiology service, but it required significant time commitments.

Background: CYP2C19 loss-of-function (LOF) alleles impair clopidogrel effectiveness after percutaneous coronary intervention. The feasibility, sustainability, and clinical impact of using CYP2C19 genotype–guided dual antiplatelet therapy (DAPT) selection in practice remains unclear. Methods: A single-center observational study was conducted in 1193 patients who underwent percutaneous coronary intervention and received DAPT after implementation of an algorithm that recommends CYP2C19 testing in high-risk patients and alternative DAPT (prasugrel or ticagrelor) in LOF allele carriers. The frequency of genotype testing and alternative DAPT selection were the primary implementation end points. Risk of major adverse cardiovascular or cerebrovascular and clinically significant bleeding events over 12 months were compared across genotype and DAPT groups by proportional hazards regression. RESULTS: CYP2C19 genotype was obtained in 868 (72.8%) patients. Alternative DAPT was prescribed in 186 (70.7%) LOF allele carriers. CYP2C19 testing ( P P =0.001) varied over time. Risk for major adverse cardiovascular or cerebrovascular was significantly higher in LOF carriers prescribed clopidogrel versus alternative DAPT (adjusted hazard ratio, 4.65; 95% confidence interval, 2.22–10.0; P P =0.347). Bleeding event rates were similar across groups (log-rank P =0.816). Conclusions: Implementing CYP2C19 genotype–guided DAPT is feasible and sustainable in a real-world setting but challenging to maintain at a consistently high level of fidelity. The higher risk of major adverse cardiovascular or cerebrovascular associated with clopidogrel use in CYP2C19 LOF allele carriers suggests that use of genotype-guided DAPT in practice may improve clinical outcomes.

Nonsteroidal antiinflammatory drugs (NSAIDs) are used in the management of a variety of conditions, but their prevalence is likely underreported as a result of widespread availability and the perception that nonprescription therapies are unnecessary to report during medication history taking. However, NSAIDs are associated with a number of adverse effects, especially in patients with cardiovascular disease (CVD). Patients with CVD and comorbidities for which NSAIDs may provide symptomatic relief (e.g., osteoarthritis, rheumatoid arthritis) tend to be older, which places them at greater risk of harm. For these reasons, the use of NSAIDs in patients with CVD is a significant public health concern. An understanding of the risks associated with NSAIDs is critical for clinicians across practice settings. In this review, we detail the safety of NSAIDs in patients with CVD, provide recommendations on their use in specific disease states, and discuss therapeutic alternatives.

Aim: An algorithm that uses clinical factors and CYP2C19 genotype to guide P2Y12 inhibitor selection in high-risk patients undergoing percutaneous coronary intervention was implemented at our institution. We sought to evaluate use of this algorithm and identify which factors influenced P2Y12 inhibitor selection. Patients & methods: This retrospective cohort study included 264 patients receiving percutaneous coronary intervention from July–December 2012. Results: CYP2C19 genotype was obtained in 229 patients; of these, 30% were intermediate or poor metabolizers. CYP2C19 intermediate or poor metabolizer phenotype was among the strongest predictors for selecting prasugrel or ticagrelor as maintenance therapy (p < 0.001), and was the only significant predictor of a change in therapy (p < 0.001). Conclusion: These findings suggest that using CYP2C19 genotype to guide P2Y12 inhibitor selection is feasible. Original submitted 27 October 2014; revision submitted 19 December 2014

Pharmacy practice models that foster pharmacists' accountability for medication-related outcomes are imperative for the profession. Comprehensive medication management (CMM) is an opportunity to advance patient care.The objective of this study was to evaluate the impact of a CMM practice model in the acute care setting on organizational, patient, and financial outcomes.Three adult service lines focused on at-risk patients identified using internal risk stratification methodology were implemented. Core CMM elements included medication reconciliation, differentiated clinical pharmacy services, inpatient MTM consultations, discharge services, and documentation. Mixed methods compared the effect of the CMM model before and after implementation. Historical patients served as comparative controls in an observational design. Pharmacists completed a 60-minute interview regarding their experiences. Qualitative data were analyzed using thematic coding to characterize perception of the model.Three pharmacists implemented the model on cardiology, hematology/oncology, and surgery transplant services and provided services to 75 patients during the study. A total of 145 medication-related problems were identified and resolved. CMM was associated with a nonsignificant reduction of 8.8% in 30-day hospital readmission rates ( P = 0.64) and a 24.9% reduction in 30-day hospital utilization ( P = 0.41) as well as a significant reduction of 86.5% in emergency department visits ( P = 0.02). Patients receiving discharge prescriptions from our outpatient pharmacies increased by 21.4%, resulting in an 11.3% increase in discharge prescription capture and additional revenue of $5780. Themes identified from qualitative interviews included CMM structure, challenges, value, and resources.This study demonstrated successful implementation of a CMM model that positively affected organizational, patient, and financial outcomes.

Previous studies have demonstrated altered hemodynamic response to intravenous inotrope in chronic, stable heart failure patients receiving beta blocker (BB). The purpose of this study is to assess the effect of BB on hemodynamic response to intravenous inotrope in patients with acute decompensated

Acute decompensated heart failure (ADHF) is associated with substantial morbidity and mortality, and represents a considerable financial burden to society. Historically, few prospective, randomized, double-blinded trials have investigated the optimal management of ADHF, and most guideline recommendations are based primarily on expert opinion. However, in the last decade, a considerable amount of research has added to the understanding of the management of ADHF in both patients with fluid overload and low cardiac output. In addition, as mechanical circulatory support devices and heart transplantation continue to evolve, significant advances have also been made with regard to the proper selection of patients for advanced surgical options. Finally, several novel pharmacologic agents have shown promise in early trials and may represent the next steps in ADHF management. Although advances have been made over the past decade, many questions remain.