Emily M. Hawes

Impact of an Outpatient Pharmacist Intervention on Medication Discrepancies and Health Care Resource Utilization in Posthospitalization Care Transitions

Purpose: Medication errors related to hospital discharge result in rehospitalization and emergency department (ED) visits, yet no systematic approach has been implemented nationally to decrease these medication errors. Pharmacist involvement during postdischarge transitions of care may be an important strategy to prevent and correct medication discrepancies and reduce costly rehospitalization and ED visits. Methods: This prospective, randomized, open-label, pilot study evaluated the effect of a pharmacy clinic visit focused on medication reconciliation and patient education after hospital discharge on the incidence of rehospitalization and ED visits and the resolution of medication discrepancies. Results: Of the 61 subjects included in the study, 33 (54%) had medication discrepancies identified at discharge. Fifty percent of medication discrepancies were resolved in subjects randomized to the pharmacist intervention arm compared with 9.5% in the usual care arm (P = .015). Patients randomized to the intervention arm had significantly lower rates of the primary composite outcome of 30-day rehospitalization and ED visits compared with the usual care arm (0% vs 40.5%, P < .001). Conclusion: A pharmacist-driven intervention focused on patient education and medication reconciliation after discharge improved medication use and reduced health care resource utilization in this pilot study.

Heparin-Calibrated Chromogenic Anti-Xa Activity Measurements in Patients Receiving Rivaroxaban: Can This Test Be Used to Quantify Drug Level?

Background: Determination of plasma rivaroxaban concentration may be necessary in certain clinical situations. Rivaroxaban concentration can be accurately and rapidly determined using a chromogenic anti–activated factor X (factor Xa) assay with specific drug calibrator material. However, there are currently no Food and Drug Administration (FDA)-approved rivaroxaban calibrators available in the United States. Objective: To determine whether FDA-approved commercial kits for measuring heparin anti–factor Xa activity can be used to assess rivaroxaban concentrations when calibrated for unfractionated heparin or low-molecular-weight heparins. Methods: Trough and peak samples were taken from 30 patients taking rivaroxaban as part of their routine care for atrial fibrillation or venous thromboembolism. The samples were tested using 3 different FDA-approved commercial kits for measuring heparin anti–factor Xa activity. Results: There was acceptable correlation between rivaroxaban levels and heparin anti–factor Xa activity using Berichrom and COAMATIC heparin kits. The STA liquid heparin method was the most sensitive to presence of rivaroxaban. Conclusion: This study demonstrates a strong correlation, but variability between kits, for assessing rivaroxaban concentrations using heparin anti–factor Xa assays. The extent of the heparin calibration curve significantly limits the measurable rivaroxaban range, and this application may be useful only for trough samples. The STA liquid heparin, being exquisitely sensitive to rivaroxaban, may be suitable for ruling out presence of the drug. The routine use of heparin-calibrated anti–factor Xa assays to quantify rivaroxaban is not advocated, and when applied, it must be used with caution and limitations clearly understood.

Performance of Various Laboratory Assays in the Measurement of Dabigatran in Patients Receiving Therapeutic Doses

OBJECTIVES To study dabigatran etexilate, a new oral anticoagulant that functions as a direct thrombin inhibitor. METHODS This study evaluates four methods, one of which is performed in three different laboratories, and compares results against dabigatran levels measured by Boehringer-Ingelheim (Ingelheim, Germany) using mass spectrometry. RESULTS Although routine monitoring is not required, measurement of plasma concentrations may be necessary in certain clinical situations. Routine coagulation assays such as the prothrombin time, activated partial thromboplastin time, and thrombin time do not reliably determine levels of dabigatran anticoagulation. Alternative assays, when calibrated with a dabigatran standard, such as the modified dilute thrombin time, ecarin clotting time, and ecarin chromogenic assay, may be appropriate, although a comparison of these methods using samples from patients taking dabigatran has not been performed. CONCLUSIONS Although results using all methods in this study demonstrate adequate correlation, measured dabigatran levels varied in a statistically significant manner, even when the same method was used by different laboratories. The clinical significance of this variation in dabigatran concentrations is uncertain.

Comparison of anti-Xa and dilute Russell viper venom time assays in quantifying drug levels in patients on therapeutic doses of rivaroxaban.

CONTEXT Rivaroxaban is a new oral anticoagulant that functions as a direct anti-Xa inhibitor. Although routine monitoring is not required, measurement of plasma concentrations may be necessary in certain clinical situations. Routine coagulation assays, such as the prothrombin time and, to a lesser degree, activated partial thromboplastin time, correlate with drug concentration, but because of reagent variability, these methods are not reliable for determining rivaroxaban anticoagulation. OBJECTIVE To compare different methods and calibrators for measuring rivaroxaban, including the chromogenic anti-Xa assay, which, when calibrated with a rivaroxaban standard, may be more appropriate for determining anticoagulation. DESIGN We compared measured rivaroxaban concentrations with the same anti-Xa kit but used different calibrators, with different anti-Xa kits but the same calibrators, with antithrombin-supplemented anti-Xa kit versus nonsupplemented kits, and with 2 methods based on rivaroxaban-calibrated, high-phospholipid, dilute Russell viper venom time. Regression and paired t test statistics were used to determine correlation and significant differences among methods and calibrator sources. RESULTS Although there was strong correlation, statistically significant biases existed among methods that report rivaroxaban levels. A single-source calibrator did not alleviate those differences among methods. High-phospholipid Russell viper venom reagents correlated with rivaroxaban concentration but were not better than chromogenic anti-Xa methods. CONCLUSIONS Rivaroxaban-calibrated, anti-Xa measurements correlate well, but the clinical significance of the variation with rivaroxaban measurements is uncertain. The antithrombin-supplemented, anti-Xa method should be avoided for measuring rivaroxaban.

Evaluating the use of commercial drug-specific calibrators for determining PT and APTT reagent sensitivity to dabigatran and rivaroxaban

Suitable laboratory methodologies for quantifying the non-vitamin K oral anticoagulants (NOAC) include liquid chromatography-tandem mass spectrometry (LC-MS/MS) or drug-calibrated assays such as the dilute thrombin time for dabigatran or anti-Xa measurements for rivaroxaban. In situations when these tests are unavailable, it has been suggested that using commercial drug calibrators on APTT and PT assays would theoretically provide reagent sensitivity to these drugs. The purpose of this study was to determine whether commercial drug calibrators deliver similar reagent sensitivity information as samples from patients receiving dabigatran or rivaroxaban as part of their routine care. Two laboratory sites tested commercial calibrator material for dabigatran and rivaroxaban (Hyphen Biomedical) using PT and APTT reagents and data was compared to samples collected from patients taking NOACs that were quantified by LC-MS/MS. Correlation statistics and calculating the amount of drug required to double the clotting time of normal plasma were performed. All drug calibrator material correlated more strongly (R²> 0.95) for any reagent/drug combination than patient samples (R² ranged from 0.29-0.86). Dabigatran calibrator results and patient data were equivalent for SynthASil and PTT-A APTT reagents. The dabigatran and rivaroxaban calibrator material over-estimated drug sensitivity for all PT reagents when compared to sensitivity data calculated based on drug levels obtained by LC-MS/MS from patient samples. In conclusion, drug-specific calibrators overestimated reagent sensitivity which may underestimate in vivo drug concentration in a given patient. Further studies are required to assess whether this method of determining relative sensitivity of NOAC on routine coagulation assays should be recommended.

Diagnosis and Management of Acute Coronary Syndrome: An Evidence-Based Update

Acute coronary syndrome (ACS) describes the range of myocardial ischemic states that includes unstable angina, non-ST elevated myocardial infarction (MI), or ST-elevated MI. ACS is associated with substantial morbidity and mortality and places a large financial burden on the health care system. The diagnosis of ACS begins with a thorough clinical assessment of a patients presenting symptoms, electrocardiogram, and cardiac troponin levels as well as a review of past medical history. Early risk stratification can assist clinicians in determining whether an early invasive management strategy or an initial conservative strategy should be pursued and can help determine appropriate pharmacologic therapies. Key components in the management of ACS include coronary revascularization when indicated; prompt initiation of dual antiplatelet therapy and anticoagulation; and consideration of adjuvant agents including β blockers, inhibitors of the renin angiotensin system, and HmG–coenzyme A reductase inhibitors. It is essential for clinicians to take an individualized approach to treatment and consider long-term safety and efficacy when managing patients with a history of ACS after hospital discharge.

Evaluation of prescribing and patient use of target‐specific oral anticoagulants in the outpatient setting

Pharmacist‐managed anticoagulation programmes have been shown to improve appropriate use of warfarin, but few programmes have included the new target‐specific oral anticoagulants (TSOACs) in their protocols. A greater understanding of TSOAC prescribing, monitoring and administration is needed to identify common errors in the current outpatient practice. The objective of this study is to assess the rate of errors related to prescribing, baseline monitoring and patient administration of TSOACs.

Genes and beans: pharmacogenomics of renal transplant

Advances in the management of patients after solid organ transplantation have led to dramatic decreases in rates of acute rejection, but long-term graft and patient survival have remained unchanged. Individualized therapy after transplant will ideally provide adequate immunosuppression while limiting the adverse effects of drug therapy that significantly impact graft survival. Therapeutic drug monitoring represents the best approximation of individualized drug therapy in transplant at this time; however, obtaining pharmacogenomic data in transplant patients has the potential to enhance our current practice. Polymorphisms of target genes that impact pharmacokinetics have been identified for most immunosuppressants, including tacrolimus, cyclosporine, mycophenolate, azathioprine and sirolimus. In the future, pre-emptive assessment of a patients genetic profile may inform drug selection and provide information on specific doses that will improve efficacy and limit toxicity.

Management of mild hypertension in adults

Elevated blood pressure is a common risk factor for cardiovascular disease and affects one in three adults. Blood pressure lowering drugs substantially reduce the risk of stroke, coronary heart disease, heart failure, and premature death, but most clinical trials showing benefits have primarily included patients with moderate to severe hypertension, known cardiovascular disease, or elevated risk of cardiovascular disease. The benefits of treating mild hypertension in patients without cardiovascular disease are less clear, but recent meta-analyses offer some insights. Pooled data from trials that include a large percentage of participants with mild hypertension show significant reductions in stroke, death from cardiovascular disease, and total mortality. Meta-analyses comparing lower blood pressure targets also suggest a benefit of treating patients with mild hypertension, although net benefits are greater for patients at higher absolute levels of cardiovascular disease risk. Before starting drug treatment, most patients should have out-of-office monitoring to confirm hypertension. Lifestyle modifications for reducing blood pressure are appropriate for all patients and may be recommended while delaying drug treatment for those at lower absolute levels of cardiovascular disease risk. Patient level control of blood pressure is supported by home monitoring and by once daily, low cost drug. Control of blood pressure for a population of patients is enhanced by system level interventions such as registries, implementation of evidence based protocols, drug titration visits, and performance metrics.

Prescribing pharmacists in the ambulatory care setting: Experience at the University of North Carolina Medical Center

PURPOSE The prescribing authorities, clinical activities, and productivity documentation strategies of ambulatory care clinic-based pharmacists practicing within a large academic health system are described. SUMMARY North Carolina law encourages progressive pharmacy practice through acquisition of the clinical pharmacist practitioner (CPP) designation. Qualified CPPs are authorized to provide collaborative drug therapy management services, including medication prescribing and ordering of laboratory tests, according to defined protocols and under physician supervision. The University of North Carolina Medical Center has approximately 30 CPPs deployed across a wide range of ambulatory care clinical practice sites. This article describes (1) the pharmacy departments implementation of an ambulatory care practice model, (2) the credentialing and privileging process leading to granting of prescribing privileges, (3) metrics used to demonstrate the impact of CPP activities, (4) recommended general criteria for ambulatory care practice site identification, and (5) strategies for overcoming barriers to successful implementation of ambulatory care-focused clinical pharmacist services. Aggregated intervention-tracking data compiled by seven of the medical centers CPP ambulatory care practice sites indicate extensive CPP involvement in direct patient care encounters and patient or provider consultations, with large numbers of medication-related interventions to support institutional cost-avoidance and revenue goals. CONCLUSION CPPs deployed at the medical centers ambulatory care clinics have had a positive impact on clinical and cost outcomes, improving patient care through interventions, contributing to readmission reduction efforts, generating indirect revenue through cost avoidance, and generating new revenue through billing for patient visits.