Canadian Stroke Best Practice Recommendations: Secondary Prevention of Stroke Update 2020.

The 2020 update of the Canadian Stroke Best Practice Recommendations (CSBPR) for the Secondary Prevention of Stroke includes current evidence-based recommendations and expert opinions intended for use by clinicians across a broad range of settings. They provide guidance for the prevention of ischemic stroke recurrence through the identification and management of modifiable vascular risk factors. Recommendations address triage, diagnostic testing, lifestyle behaviors, vaping, hypertension, hyperlipidemia, diabetes, atrial fibrillation, other cardiac conditions, antiplatelet and anticoagulant therapies, and carotid and vertebral artery disease. This update of the previous 2017 guideline contains several new or revised recommendations. Recommendations regarding triage and initial assessment of acute transient ischemic attack (TIA) and minor stroke have been simplified, and selected aspects of the etiological stroke workup are revised. Updated treatment recommendations based on new evidence have been made for dual antiplatelet therapy for TIA and minor stroke; anticoagulant therapy for atrial fibrillation; embolic strokes of undetermined source; low-density lipoprotein lowering; hypertriglyceridemia; diabetes treatment; and patent foramen ovale management. A new section has been added to provide practical guidance regarding temporary interruption of antithrombotic therapy for surgical procedures. Cancer-associated ischemic stroke is addressed. A section on virtual care delivery of secondary stroke prevention services in included to highlight a shifting paradigm of care delivery made more urgent by the global pandemic. In addition, where appropriate, sex differences as they pertain to treatments have been addressed. The CSBPR include supporting materials such as implementation resources to facilitate the adoption of evidence into practice and performance measures to enable monitoring of uptake and effectiveness of recommendations.

Jurisdictional Guidance on DOAC Use-Will It Affect Practice? A Comparison of European, American, and Canadian Product Monographs.

Objective: To identify clinically relevant areas of concordance and discordance between product monographs for 4 direct oral anticoagulants (DOACs) approved by regulatory authorities in Europe, the United States, and Canada. Data Sources: For each DOAC (apixaban, dabigatran, edoxaban, rivaroxaban), manufacturer product monographs were retrieved from the European Medicines Database, US Food and Drug Administration, and Health Canada Drug Product Database. Data Extraction: Monographs for each DOAC were independently reviewed by 2 investigators to identify areas of concordance and discordance. Discordance existed if it was deemed that a potentially clinically relevant difference existed. A heat map summarizing the data was created to identify areas of complete concordance, partial concordance (concordance between 2 of 3 monographs), and complete discordance. Data Synthesis: The areas of concordance were indications for use, use in extremes of weight, and switching to/from the DOAC. Areas of discordance included the following: differing recommendations for use/dosing with renal dysfunction; contraindication or use with caution with drug interactions, pregnancy, and hepatic/renal dysfunction; and timing of DOAC with spinal/epidural anesthesia after a procedure or traumatic puncture. Relevance to Patient Care and Clinical Practice: Concordance was most evident for uncomplicated patients with atrial fibrillation or venous thromboembolism, whereas discordance emerged for those having characteristics/factors wherein clinicians may seek clarification within product monographs (eg, impaired renal/hepatic function, drug interactions). As such, clinicians must be familiar with product information within their country of practice. Conclusion: Variability between jurisdictions was evident, and variability of DOAC use is likely to increase with expanding worldwide uptake.

Use of low-dose acetylsalicylic acid for cardiovascular disease prevention: A practical, stepwise approach for pharmacists.

Low-dose acetylsalicylic acid (ASA) is recommended in patients with established cardiovascular disease. However, the role of ASA in those without cardiovascular disease (i.e., primary prevention) is less clear, which has led to discordance among Canadian guidelines. In 2018, 3 double-blind, randomized controlled trials were published that evaluated ASA 100 mg daily versus placebo in patients without established cardiovascular disease. In the ASPREE trial, ASA did not reduce the risk of all-cause death, dementia, or persistent physical disability in patients ≥70 years of age but increased the risk of major bleeding. In the ARRIVE trial, ASA failed to lower the risk of a composite of cardiovascular events but increased any gastrointestinal bleeding in patients at intermediate risk of cardiovascular disease. In the ASCEND trial, ASA significantly reduced the primary composite cardiovascular outcome in patients with diabetes for a number needed to treat of 91 over approximately 7.4 years. Yet major bleeding was increased with ASA for a number needed to harm of 112. Therefore, in most situations, ASA should not be recommended for primary cardiovascular prevention. However, there are additional indications for ASA beyond cardiovascular disease. Thus, a sequential algorithm was developed based on contemporary evidence to help pharmacists determine the suitability of ASA in their patients and play an active role in educating their patients about the potential benefits (or lack thereof) and risks of ASA. Can Pharm J (Ott) 2020;153:xx-xx.

Development of clinical pharmacy key performance indicators for hospital pharmacists using a modified Delphi approach.

BACKGROUND: Key performance indicators (KPIs) are quantifiable measures of quality. There are no published, systematically derived clinical pharmacy KPIs (cpKPIs). OBJECTIVE: A group of hospital pharmacists aimed to develop national cpKPIs to advance clinical pharmacy practice and improve patient care. METHODS: A cpKPI working group established a cpKPI definition, 8 evidence-derived cpKPI critical activity areas, 26 candidate cpKPIs, and 11 cpKPI ideal attributes in addition to 1 overall consensus criterion. Twenty-six clinical pharmacists and hospital pharmacy leaders participated in an internet-based 3-round modified Delphi survey. Panelists rated 26 candidate cpKPIs using 11 cpKPI ideal attributes and 1 overall consensus criterion on a 9-point Likert scale. A meeting was facilitated between rounds 2 and 3 to debate the merits and wording of candidate cpKPIs. Consensus was reached if 75% or more of panelists assigned a score of 7 to 9 on the consensus criterion during the third Delphi round. RESULTS: All panelists completed the 3 Delphi rounds, and 25/26 (96%) attended the meeting. Eight candidate cpKPIs met the consensus definition: (1) performing admission medication reconciliation (including best-possible medication history), (2) participating in interprofessional patient care rounds, (3) completing pharmaceutical care plans, (4) resolving drug therapy problems, (5) providing in-person disease and medication education to patients, (6) providing discharge patient medication education, (7) performing discharge medication reconciliation, and (8) providing bundled, proactive direct patient care activities. CONCLUSIONS: A Delphi panel of hospital pharmacists was successful in determining 8 consensus cpKPIs. Measurement and assessment of these cpKPIs will serve to advance clinical pharmacy practice and improve patient care.

Characterization of Antithrombotic Regimens for Patients with Nonvalvular Atrial Fibrillation and Obesity Discharged from Cardiology Wards.

Background: Despite data derived from observational studies, optimal anticoagulation strategies have yet to be established for patients with nonvalvular atrial fibrillation and obesity. Objective: To describe direct oral anticoagulant (DOAC) regimens prescribed for adult patients with nonvalvular atrial fibrillation who weighed more than 120 kg. Methods: This single-centre, retrospective cohort study, conducted in the Saskatchewan Health Authority - Regina Area, involved adult patients with body weight greater than 120 kg who had an indication for oral anticoagulation to treat nonvalvular atrial fibrillation and were discharged by a cardiologist between June 2019 and July 2021. Results: A total of 62 patients were included (median weight 135 kg). At discharge, DOACs were prescribed for 57 (92%) of the patients and warfarin for 5 (8%). In numeric terms, patients receiving warfarin were at higher risk of thromboembolism or thrombosis; however, the small sample size limited the ability to draw conclusions. Conclusions: Practice patterns in the Saskatchewan Health Authority - Regina Area indicated substantial use of DOACs for patients with body weight greater than 120 kg; however, for those with the highest weights, warfarin was still in use.

Contexte: Malgré les données dérivées d'études observationnelles, les stratégies d'anticoagulation optimales n'ont pas été consolidées pour les patients atteints de fibrillation auriculaire non valvulaire et d'obésité. Objectif: Décrire les schémas thérapeutiques d'anticoagulants oraux (ACO) prescrits aux patients adultes atteints de fibrillation auriculaire non valvulaire et qui pesaient plus de 120 kg. Méthodes: Cette étude de cohorte rétrospective monocentrique menée dans l'office de la santé de la Saskatchewan à Regina a porté sur des patients adultes pesant plus de 120 kg qui avaient une indication de traitement anticoagulant oral pour traiter la fibrillation auriculaire non valvulaire et qui ont été renvoyés par un cardiologue entre juin 2019 et juillet 2021. Résultats: Au total, 62 patients ont été inclus (poids médian, 135 kg). Au congé, des ACO ont été prescrits à 57 (92 %) des patients et de la warfarine à 5 (8 %) d'entre eux. En termes numériques, les patients traités par warfarine présentaient un risque plus élevé de thromboembolie ou de thrombose; cependant, la petite taille de l'échantillon a limité la capacité de tirer des conclusions. Conclusions: Les modèles de pratique de l'office de la santé de la Saskatchewan à Regina indiquaient une utilisation importante des ACO pour les patients dont le poids corporel était supérieur à 120 kg; cependant, pour les personnes ayant le poids le plus élevé, la warfarine était toujours utilisée.

Anticoagulation Interventions by Pharmacists in Acute Care.

Background: Clinical pharmacy key performance indicators (cpKPIs) relate to activities performed by pharmacists that have been shown to improve patient outcomes. Within Saskatchewan Health Authority (SHA) Regina, most cpKPIs are incorporated into the organization's clinical practice standards, which provide guidance in prioritizing care, especially for high-risk medications, including anticoagulants. To track pharmacists' interventions associated with clinical practice standards, a locally developed electronic data-capture system (known as AIM High) was implemented. Objectives: To quantify and describe pharmacists' anticoagulation interventions on 16 wards with dedicated ward-based clinical pharmacists and to compare intervention rates between the cardiology and internal medicine wards to further evolve the organization's practice model. Methods: Data from the electronic data-capture system were retrospectively analyzed for a 5-year period (January 2016 to December 2020). Results: A total of 94 201 interventions were recorded in the AIM High system (average 362 interventions per week or 26 interventions per pharmacist per week). Of these, 15 661 (16.6%) cited the anticoagulation standard (average 60 anticoagulation interventions per week or 4 anticoagulant interventions per pharmacist per week). For the cardiology and internal medicine wards, 4183 of 11 888 (35.2%) and 9034 of 54 843 (16.5%) interventions cited the anticoagulation standard, respectively. The top 4 types of anticoagulation interventions were dose changed (n = 4372 or 27.9%), drug started or restarted (n = 3867 or 24.7%), patient education (n = 3094 or 19.8%), and drug discontinued (n = 2944 or 18.8%). Conclusion: Dedicated ward-based clinical pharmacists were following clinical practice standards incorporating the majority of cpKPIs to complete anticoagulation interventions. The types of anticoagulation interventions evolved over time and were influenced by the patient population.

Contexte: Les indicateurs clés de performance en pharmacie clinique (ICPEPC) se rapportent à des activités exécutées par des pharmaciens qui ont fait leurs preuves dans l'amélioration des résultats pour les patients. À la Saskatchewan Health Authority (SHA) Regina, la plupart des ICPEPC sont intégrés aux normes de pratique clinique de l'organisme. Celles-ci fournissent des conseils pour hiérarchiser les soins liés aux médicaments, en particulier ceux associés aux médicaments à haut risque, notamment les anticoagulants. Un système électronique de saisie de données développé localement, le « AIM High ¼, a été mis en place afin de suivre les interventions des pharmaciens associées aux normes de pratique clinique. Objectifs: Quantifier et décrire les interventions des pharmaciens en matière d'anticoagulation dans 16 services avec des pharmaciens cliniciens dédiés et comparer les taux d'intervention entre les services de cardiologie et de médecine interne en vue de faire évoluer davantage le modèle de pratique de l'organisation. Méthodes: Les données du système électronique de saisie des données ont été analysées rétrospectivement sur une période de 5 ans (de janvier 2016 à décembre 2020). Résultats: Au total, 94 201 interventions ont été enregistrées dans le système (moyenne de 362 interventions par semaine ou 26 interventions par pharmacien par semaine). Parmi celles-ci, 15 661 (16,6 %) citent la norme d'anticoagulation (moyenne de 60 interventions d'anticoagulation par semaine ­ soit 4 interventions d'anticoagulation par pharmacien par semaine). Pour les services de cardiologie et de médecine interne, 4183 (35,2%) des 11 888 et 9034 (16,5 %) des 54 843 interventions citent respectivement la norme d'anticoagulation. Les 4 principaux types d'interventions d'anticoagulation étaient le changement de dose (n = 4372 ou 27,9 %), le traitement commencé ou redémarré (n = 3867 ou 24,7 %), l'éducation du patient (n = 3094 ou 19,8 %) et l'arrêt du médicament (n = 2944 ou 18,8 %). Conclusion: Les pharmaciens cliniques dédiés au service suivaient les normes de pratique clinique incorporant la majorité des ICPEPC pour mener à bien les interventions d'anticoagulation. Les types d'interventions d'anticoagulation ont évolué au fil du temps et ont été influencés par la population de patients.

Prevention and treatment of venous thromboembolism in patients with cancer.

BACKGROUND: Many patients who experience a venous thromboembolic event have cancer, and thrombosis is much more prevalent in patients with cancer than in those without it. Thrombosis is the second most common cause of death in cancer patients and cancer is associated with a high rate of recurrence of venous thromboembolism (VTE), bleeding, requirement for long-term anticoagulation and poorer quality of life. METHODS: A literature review was conducted to identify guidelines and evidence pertaining to anticoagulation prophylaxis and treatment for patients with cancer, with the goal of identifying opportunities for pharmacists to advocate for and become more involved in the care of this population. RESULTS: Many clinical trials and several guidelines providing guidance to clinicians in the treatment and prevention of VTE in patients with cancer were identified. Current clinical evidence and guidelines suggest that cancer patients receiving care in hospital with no contraindications should receive VTE prophylaxis with unfractionated heparin (UFH), a low-molecular-weight heparin (LMWH) or fondaparinux. Patients who require surgery for their cancer should receive prophylaxis with UFH, LMWH or fondaparinux. Cancer patients who have experienced a VTE event should receive prolonged anticoagulant therapy with LMWH (at least 3 months to 6 months). No routine prophylaxis is required for the majority of ambulatory patients with cancer who have not experienced a VTE event. Most publicly funded drug plans in Canada have developed criteria for funding of LMWH therapy for patients with cancer. CONCLUSIONS: Evidence suggests that LMWH for 3 to 6 months is the preferred strategy for most cancer patients who have experienced a thromboembolic event and for hospital inpatients, but this is often not implemented in practice. Concerns about adherence with injectable therapy should not prevent use of these agents. Pharmacists should assess cancer patients for their risk of VTE and should advocate for optimal VTE pharmacotherapy as appropriate. If LMWH is the preferred agent, on the basis of the evidence, the pharmacist should educate the patients appropriately and work with the prescriber to ensure best care.

Pharmacokinetics of apixaban and tacrolimus or cyclosporine in kidney and lung transplant recipients.

Apixaban is frequently used off-label in transplant recipients. However, a potential drug interaction exists with the calcineurin inhibitors. We conducted an open-label drug-drug interaction study to determine the pharmacokinetics of apixaban in lung and kidney transplant recipients who were taking a calcineurin inhibitor. A single dose of apixaban 10 mg was administered orally to kidney and lung transplant recipients maintained on either tacrolimus or cyclosporine, and pharmacokinetic parameters were compared to a reference cohort of 12 healthy subjects who used the same apixaban dose and pharmacokinetic blood sampling. Fourteen participants were enrolled (n = 6 kidney, n = 8 lung), with 10 maintained on tacrolimus and four on cyclosporine. Data from 13 participants was usable. Participants were taking triple therapy immunosuppression and had a mean (SD) of 12 (3) medications. Participants receiving tacrolimus and cyclosporine had area under the plasma concentration-time curve from time zero to infinity (AUC0-inf ) geometric least square means (90% confidence interval [CI]) of 4312 (95% CI 3682, 5049) and 5388 (95% CI 3277, 8858), respectively. Compared to healthy subjects, the associated geometric mean ratios (GMRs) for apixaban maximum plasma concentration (Cmax ), AUC from time zero to the last quantifiable concentration (AUC0-tlast ) and AUC0-inf were 197% (95% CI 153, 295), 244% (95% CI 184, 323), and 224% (95% CI 170, 295) for transplant recipients on tacrolimus. The GMR (90% CI) Cmax , AUC0-tlast , and AUC0-inf of apixaban for patients on cyclosporine were 256% (95% CI 184, 358), 287% (95% CI 198, 415), and 280% (95% CI 195, 401). Kidney and lung transplant recipients receiving tacrolimus had higher apixaban exposure. A similar trend was noted for patients receiving cyclosporine, but additional patients are needed to confirm this interaction. Future studies are needed before apixaban can be safely recommended in this population, and the impact of dose staggering should be investigated. This study highlights the importance of pharmacokinetic studies in actual patient populations.