Stroke Risk Reduction in Atrial Fibrillation Through Pharmacist Prescribing: A Randomized Clinical Trial.

Importance: Major gaps in the delivery of appropriate oral anticoagulation therapy (OAC) exist, leaving a large proportion of persons with atrial fibrillation (AF) unnecessarily at risk for stroke and its sequalae. Objective: To investigate whether pharmacist-led OAC prescription can increase the delivery of stroke risk reduction therapy in individuals with AF. Design, Setting, and Participants: This prospective, open-label, patient-level randomized clinical trial of early vs delayed pharmacist intervention from January 1, 2019, to December 31, 2022, was performed in 27 community pharmacies in Alberta, Canada. Pharmacists identified patients 65 years or older with 1 additional stroke risk factor and known, untreated AF (OAC nonprescription or OAC suboptimal dosing) or performed screening using a 30-second single-lead electrocardiogram to detect previously unrecognized AF. Patients with undertreated or newly diagnosed AF eligible for OAC therapy were considered to have actionable AF. Data were analyzed from April 3 to November 30, 2023. Interventions: In the early intervention group, pharmacists prescribed OAC using guideline-based algorithms with follow-up visits at 1 and 3 months. In the delayed intervention group, which served as the usual care control, the primary care physician (PCP) was sent a notification of actionable AF along with a medication list (both enhancement over usual care). After 3 months, patients without OAC optimization in the control group underwent delayed pharmacist intervention. Main Outcomes and Measures: The primary outcome was the difference in the rate of guideline-concordant OAC use in the 2 groups at 3-month follow-up ascertained by a research pharmacist blinded to treatment allocation. Results: Eighty patients were enrolled with actionable AF (9 [11.3%] newly diagnosed in 235 individuals screened). The mean (SD) age was 79.7 (7.4) years, and 45 patients (56.3%) were female. The median CHADS2 (congestive heart failure, hypertension, age, diabetes, and stroke or transient ischemic attack) score was 2 (IQR, 2-3). Seventy patients completed follow-up. Guideline-concordant OAC use at 3 months occurred in 36 of 39 patients (92.3%) in the early intervention group vs 23 of 41 (56.1%) in the control group (P < .001), with an absolute increase of 34% and number needed to treat of 3. Of the 23 patients who received appropriate OAC prescription in the control group, the PCP called the pharmacist for prescribing advice in 6 patients. Conclusions and Relevance: This randomized clinical trial found that pharmacist OAC prescription is a potentially high-yield opportunity to effectively close gaps in the delivery of stroke risk reduction therapy for AF. Scalability and sustainability of pharmacist OAC prescription will require larger trials demonstrating effectiveness and safety. Trial Registration: ClinicalTrials.gov Identifier: NCT03126214.

Anticoagulant Prescribing Patterns in New-Onset Atrial Fibrillation After Cardiac Surgery.

BACKGROUND: Postoperative atrial fibrillation (POAF) is a common complication after cardiac surgery and is associated with an increased risk of thromboembolic stroke. Recommendations regarding the optimal anticoagulant, timing of initiation, and duration of therapy remain uncertain. METHODS: Administrative databases were used to include adult patients who presented with POAF after cardiac surgery between January 1, 2015, and December 31, 2020. Key exclusion criteria included preexisting atrial fibrillation, mechanical valve replacement, or anticoagulant prescription fill within 6 months before the index admission. RESULTS: A total of 3214 of patients were included, and 878 (27.3%) were prescribed an oral anticoagulant (OAC) on discharge, with 536 (61%) prescribed warfarin and 342 (39%) prescribed a direct OAC. More than half of the patients (56.1%) stopped their OAC by 6 months. There was no difference in stroke or systemic embolism at 30 days, 3 months, or 6 months between those with and without anticoagulation prescribed. However, those on any OAC had higher rates of any bleeding at all time points. CONCLUSIONS: A minority of patients who presented with POAF after cardiac surgery were prescribed OAC, with warfarin being the most common agent. OAC initiation was associated with increased bleeding risk, warranting special consideration when assessing a patient's risk of stroke with the increased risk of bleeding, particularly in the postoperative period.

Choice of Oral Anticoagulant: Outcomes in Atrial Fibrillation Patients Post-Stroke Despite Direct Oral Anticoagulant Use.

Background: For patients with atrial fibrillation who have an ischemic stroke or transient ischemic attack (TIA) despite taking direct oral anticoagulants (DOACs), the optimal strategy for ongoing anticoagulation is unknown. Methods: Using provincial administrative databases in Alberta, Canada, we compared anticoagulant use before/after the breakthrough stroke/TIA and assessed recurrence of stroke/TIA or bleeding, with consideration of medication adherence. Adherence was defined as the proportion of days covered (PDC) being ≥ 80%. Results: Among 985 patients, the median age was 80 years (interquartile range 13), with a mean CHADS2 score of 1.7± 1 prior to the index event. Patients were followed for a median of 643 days (interquartile range 836). Following the index stroke/TIA event, 623 patients (63%) filled a prescription for the same DOAC regimen, 83 (8%) filled a prescription for a different dose, 155 (16%) switched DOAC agents, 51 (5%) switched to warfarin, and 73 (7%) filled no oral anticoagulant prescription. Patients who kept the same regimen more commonly had TIA index events (59%); patients who changed dose or drug more often had stroke index events (55%-78%). During follow-up, 135 (14%) had stroke/TIA recurrence, and 46 (5%) had bleeding; rates of each did not differ between prescribing patterns. Post-index event, the proportion of patients with a proportion of days covered ≥ 80% improved from 55% to 80%. Conclusions: Although most maintained the same DOAC regimen after stroke/TIA, rates of recurrent stroke/TIA and bleeding were similar across prescribing patterns. Stroke/TIA severity may have influenced prescribing practices. DOAC prescription adherence improved poststroke/TIA and signals an opportunity for optimization in patients with atrial fibrillation.

Contexte: Chez les patients atteints de fibrillation auriculaire qui subissent un accident vasculaire cérébral (AVC) ischémique ou un accident ischémique transitoire (AIT) malgré la prise d'anticoagulants oraux directe (AOD), la stratégie optimale pour la poursuite de l'anticoagulation est inconnue. Méthodologie: À partir des bases de données administratives provinciales en Alberta, au Canada, nous avons comparé l'utilisation d'anticoagulants avant/après l'AVC/AIT survenu pendant l'anticoagulothérapie et avons évalué la récurrence d'un AVC/AIT ou d'un saignement, en tenant compte de l'adhésion au traitement médicamenteux. L'adhésion a été définie comme une proportion de jours couverts (PJC) de 80 % ou plus. Résultats: Chez 985 patients, l'âge médian était de 80 ans (écart interquartile de 13) et le score CHADS2 moyen, de 1,7 ± 1 avant l'événement de référence. Les patients ont été suivis pendant une médiane de 643 jours (écart interquartile de 836). Après l'AVC/AIT de référence, 623 patients (63 %) ont fait exécuter une ordonnance du même schéma d'AOD, 83 (8 %) ont fait exécuter une ordonnance d'une dose différente, 155 (16 %) sont passés à d'autres AOD, 51 (5 %) sont passés à la warfarine et 73 (7 %) n'ont fait exécuter aucune ordonnance d'anticoagulant oral. Chez les patients qui ont continué à recevoir le même schéma, la plupart (59 %) avaient eu un AIT comme événement de référence; chez les patients qui ont changé de dose ou de médicament, la plupart (55 à 78 %) avaient eu un AVC comme événement de référence. Durant le suivi, 135 (14 %) ont connu un AVC/AIT récurrent et 46 (5 %) ont présenté un saignement; les taux de chaque manifestation ont été similaires pour les différents schémas de prescription. Après l'événement de référence, le pourcentage de patients ayant une PJC ≥ 80 % a augmenté, passant de 55 à 80 %. Conclusions: Malgré le maintien du même schéma d'AOD chez la plupart des patients après l'AVC/AIT, les taux d'AVC/AIT récurrent et de saignement ont été similaires avec tous les schémas de prescription. La gravité d'un AVC/AIT pourrait avoir influencé les pratiques de prescription. L'adhésion aux AOD prescrits s'est améliorée après un AVC/AIT et témoigne d'une possibilité d'optimisation chez les patients atteints de fibrillation auriculaire.

Effects of a Computerized Prescriber Order Entry System on Pharmacist Prescribing.

Background: In Alberta, pharmacists are eligible to obtain additional prescribing authority (APA). At the University of Alberta Hospital, a transition was made from a paper-based prescriber order entry system to a computerized prescriber order entry (CPOE) system. Objectives: The primary objective was to quantify any change in pharmacist prescribing after CPOE implementation. The secondary objective was to compare the paper-based and CPOE systems in terms of drug schedule, order type, medication class, and the pharmacist's area of clinical practice. Methods: A retrospective comparative review of pharmacist orders was completed using 2-week periods of data from each of the paper-based order entry system and the CPOE system, spaced 1 year apart (in January 2019 and January 2020). Results: Pharmacists prescribed a mean of 3.76 (95% confidence interval 1.97-5.96) more orders per day within the CPOE system than in the paper-based system (p < 0.001). Schedule I medications accounted for a higher proportion of pharmacists' prescriptions in the CPOE system than in the paper-based system (77.7% versus 70.5%, p < 0.001). In terms of order type, discontinuation orders accounted for a much higher proportion of pharmacists' orders in the CPOE system than in the paper-based order entry system (58.0% versus 19.8%, p < 0.001). Conclusions: This study showed that a CPOE system resulted in more use of APA by pharmacists, with schedule I medications accounting for a higher proportion of pharmacists' prescriptions. With the CPOE system, pharmacists used their prescribing privileges to discontinue a higher proportion of orders than was the case with the paper-based system. Therefore, the CPOE system is a potential facilitator of pharmacist prescribing.

Contexte: En Alberta, les pharmaciens peuvent obtenir des pouvoirs de prescription supplémentaires (PPS). À l'hôpital de l'Université de l'Alberta, le système de saisie des ordonnances est passé d'un système sur papier à un système de saisie électronique des ordonnances (SSEO) par les prescripteurs. Objectifs: L'objectif principal consistait à quantifier tout changement dans la prescription des pharmaciens après la mise en place du SSEO. L'objectif secondaire visait à comparer le système sur papier et le SSEO en matière d'annexe des médicaments, de type d'ordonnance, de catégorie de médicament et de domaine de pratique clinique du pharmacien. Méthodes: Un examen comparatif rétrospectif des ordonnances des pharmaciens a été réalisé à l'aide de périodes de données de 2 semaines provenant de chacun des systèmes (papier et électronique), avec un intervalle d'un an (janvier 2019 et janvier 2020). Résultats: Les pharmaciens prescrivaient en moyenne 3,76 (intervalle de confiance à 95 % 1,97­5,96) ordonnances de plus par jour avec le SSEO qu'avec le système sur papier (p < 0,001). La part des ordonnances de médicaments de l'annexe I était plus importante avec le SSEO qu'avec le système sur papier (77,7 % contre 70,5 %, p < 0,001). En ce qui concerne le type d'ordonnance, la part des ordonnances de cessation était beaucoup plus élevée avec le SSEO qu'avec le système de saisie sur papier (58,0 % contre 19,8 %, p < 0,001). Conclusions: Cette étude a démontré un plus grand recours au PPS lorsque les pharmaciens utilisaient un SSEO et les médicaments de l'annexe I représentant une proportion plus élevée des ordonnances. Avec le SSEO, les pharmaciens ont utilisé leur pouvoir de prescription pour interrompre une part plus élevée d'ordonnances que ce n'était le cas avec le système sur papier. Le SSEO est donc un facilitateur potentiel de la prescription par les pharmaciens.

The Role of Home Care Pharmacists in the Edmonton Zone: A Retrospective Study.

Background: Despite the rising demand for home-based health care services in Canada and the increasing medical complexity of elderly patients, there is limited literature exploring the role of home care pharmacists and the clinical activities they perform. Objectives: The primary objective was to describe the types and frequencies of clinical activities (both interventions and recommendations) performed by home care pharmacists upon initial consultation. The secondary objective was to determine which patient characteristics resulted in the highest number of clinical activities. Methods: This study was a retrospective review of adult patients who had an initial in-person or telemedicine consultation with home care pharmacists from June 2018 to May 2019 in the Edmonton Zone of Alberta Health Services. Results: Of the 355 patients whose records were screened, 318 (89.6%) were included in the analysis. Of these, 191 (60.1%) were female, and the median age was 79 years (interquartile range [IQR] 68-86 years). The median numbers of medical conditions and medications were 6 and 10, respectively. Of the total of 1172 clinical activities, there was a median of 3 (IQR 2-5) per patient, irrespective of the patient's medical conditions, including those with the most common conditions. The most common activities were patient counselling (n = 160, 13.7%), collaboration with another health care professional (n = 157, 13.4%), and deprescribing (n = 140, 11.9%). Across all activities, pharmacists performed a total of 562 interventions and made 610 recommendations. Each additional year of age and each additional medication on a patient's medication list resulted in an increase in the number of clinical activities (by 0.01 for each additional year of age [p = 0.003] and by 0.03 for each additional medication [p < 0.001]). Conclusions: Home care pharmacists in the Edmonton Zone performed a wide range of clinical activities, particularly for older patients and those with more medications. Further research is required to evaluate the outcomes of pharmacist consultations.

Contexte: Malgré l'augmentation de la demande de services de soins de santé à domicile au Canada et la complexité médicale croissante des patients âgés, il existe peu de documentation examinant le rôle des pharmaciens au sein de l'équipe de soins à domicile et leurs activités cliniques. Objectifs: L'objectif primaire consistait à décrire le type et la fréquence des activités cliniques (interventions et recommandations) effectuées par les pharmaciens à domicile lors de la consultation initiale. L'objectif secondaire consistait quant à lui à déterminer les caractéristiques des patients qui ont entraîné le plus grand nombre d'activités cliniques. Méthodes: Cette étude était une revue rétrospective de patients adultes ayant eu une première consultation en personne ou par télémédecine avec des pharmaciens de soins à domicile de juin 2018 à mai 2019 dans la zone d'Edmonton des services de soins de santé de l'Alberta. Résultats: Sur les 355 patients dont les dossiers ont été examinés, 318 (89,6 %) ont été inclus dans l'analyse. Parmi eux, l'âge médian était de 79 ans (écart interquartile [IQR] 68­86) et 191 (60,1 %) étaient des femmes. Le nombre médian de problèmes médicaux et de médicaments était respectivement de 6 et 10. Sur les 1172 activités cliniques au total, le nombre médian était de 3 activités (IQR 2­5) par patient, indépendamment de ses problèmes médicaux, y compris ceux présentant les maladies les plus courantes. Les activités les plus courantes étaient le conseil aux patients (n = 160, 13,7 %), la collaboration avec un autre fournisseur de soins de santé (n = 157, 13,4 %) et la déprescription (n = 140, 11,9 %). Toutes activités confondues, les pharmaciens ont effectué 562 interventions et fait 610 recommandations. Chaque année d'âge supplémentaire et chaque médicament ajouté à la liste des médicaments donnaient lieu à une augmentation du nombre d'activités cliniques (de 0,01 pour chaque année d'âge supplémentaire [p = 0,003] et de 0,03 pour chaque médicament supplémentaire [p < 0,001]). Conclusions: Les pharmaciens de soins à domicile de la zone d'Edmonton effectuaient un large éventail d'activités cliniques, en particulier pour les patients âgés et ceux prenant plus de médicaments. Des recherches supplémentaires sont nécessaires pour évaluer les résultats des consultations des pharmaciens.

Prevalence of Venous Thromboembolism and Anticoagulant Use in Patients with COVID-19 in Alberta, Canada.

Background: COVID-19 causes a hypercoagulable state and increases the risk of venous thromboembolism (VTE). Objectives: The primary objective was to identify VTE prevalence among patients with COVID-19 in one Canadian province. Secondary objectives were to identify the prevalence of bleeding, describe anticoagulation prescribing practices, and identify factors contributing to VTE in these patients. Methods: Adult patients admitted to Alberta hospitals between March and December 2020 with COVID-19 who had a length of stay of at least 72 hours were included in this retrospective study. VTE, bleeding events, and comorbidities were defined by International Classification of Diseases and Related Health Problems, 10th Revision codes. Cases of VTE and controls (no VTE) were matched on the basis of age older than 60 years, active cancer, and length of stay for the full cohort, as well as for a subgroup of patients with d-dimer data available, to assess for factors associated with VTE. Results: A total of 2544 patients were included. Median age was 66 years, 1461 patients (57.4%) were male, median weight was 77.7 kg, and median d-dimer level on admission was 1.00 mg/L. The prevalence of VTE was 3.7% (n = 93) and that of major and clinically relevant non-major bleeding was 4.9% (n = 125). Of the total population, 1224 patients (48.1%) had standard prophylactic-dose anticoagulation, 460 (18.1%) received only higher-dose anticoagulation, 248 (9.7%) received both prophylactic- and higher-dose anticoagulation, and 612 (24.1%) had no anticoagulation data. Logistic regression showed that only the presence of d-dimer above 3 mg/L was associated with a significant odds ratio for VTE (7.04, 95% confidence interval 2.43-20.84). Conclusions: VTE prevalence among patients with COVID-19 was higher than baseline prevalence in Alberta. Analysis of prescribing practices demonstrated that a large proportion of patients received higher-dose anticoagulation.

Contexte: La COVID-19 provoque un état d'hypercoagulabilité et augmente le risque de thromboembolie veineuse (TEV). Objectifs: L'objectif principal de cette étude consistait à identifier la prévalence de la TEV chez les patients atteints de COVID-19 dans une province canadienne. Ses objectifs secondaires consistaient, quant à eux, à identifier la prévalence des saignements, décrire les pratiques relatives à la prescription d'anticoagulants et à identifier les facteurs contribuant à la TEV chez ces patients. Méthodes: Cette étude rétrospective a été menée auprès de patients adultes atteints de COVID-19 admis dans les hôpitaux de l'Alberta entre mars et décembre 2020 avec une durée de séjour d'au moins 72 heures. La TEV, les événements hémorragiques et les comorbidités étaient définis par les codes de la Classification internationale des maladies et des problèmes de santé connexes, 10 e révision (CIM-10). Les cas de TEV et les témoins (sans TEV) ont été appariés sur les bases suivantes afin d'évaluer les facteurs associés à la TEV : âge de plus de 60 ans, cancer actif et durée de séjour pour l'ensemble de la cohorte, ainsi que pour un sous-groupe de patients dont les données sur les D-dimères étaient disponibles. Résultats: Au total, 2544 patients ont été inclus. L'âge médian était de 66 ans; 1461 patients (57,4 %) étaient des hommes; leur poids médian était de 77,7 kg et le taux médian de D-dimères à l'admission était de 1,00 mg/L. La prévalence de la TEV était de 3,7 % (n = 93) et celle des saignements majeurs et non majeurs cliniquement pertinents était de 4,9 % (n = 125). Sur la population totale, 1224 patients (48,1 %) ont reçu un anticoagulant à dose prophylactique standard; 460 (18,1 %) n'ont reçu qu'un anticoagulant à dose plus élevée; 248 (9,7 %) ont reçu à la fois un anticoagulant à dose prophylactique et à dose plus élevée; et 612 (24,1 %) ne disposaient pas de données relatives à la prescription d'anticoagualant. La régression logistique a montré que seule la présence de D-dimères au-dessus de 3 mg/L était associée à un rapport de cotes significatif pour la TEV (7,04, intervalle de confiance à 95 % 2,43­20,84). Conclusions: La prévalence de la TEV chez les patients atteints de COVID-19 était plus élevée que la prévalence de référence en Alberta. L'analyse des pratiques de prescription a montré qu'une grande proportion de patients recevait un anticoagulant à plus forte dose.

Effect of New Evidence on Antithrombotic Therapies in Atrial Fibrillation Patients Who Undergo Percutaneous Coronary Intervention in Alberta, Canada.

Background: Trials have addressed the combined use of direct oral anticoagulants (DOACs) and antiplatelets in atrial fibrillation (AF) patients undergoing percutaneous coronary intervention (PCI). These trials may have changed prescribing patterns. Methods: This administrative audit of Albertans with AF undergoing PCI described antithrombotic therapy before vs after publication of the PIONEER AF-PCI (An Open-label, Randomized, Controlled, Multicenter Study Exploring Two Treatment Strategies of Rivaroxaban and a Dose-Adjusted Oral Vitamin K Antagonist Treatment Strategy in Patients With Atrial Fibrillation Who Undergo Percutaneous Coronary Intervention) trial results. Results: Cohorts were similar before (n = 597) and after (n = 708) trial publication: median age 72 years; 23% female; 63% with acute coronary syndrome; and 22% with bleeding history. Anticoagulant use increased by 7.0% (P = 0.01) after; with DOAC use increasing by 24.9% and warfarin use decreasing by 17.5% (P < 0.0001). DOAC use was associated with being in the "after" cohort (odds ratio 5.42, 95% confidence interval 3.75-7.82, P < 0.0001). Conclusions: Significantly more patients were prescribed anticoagulation therapy after the publication of the results of the PIONEER AF-PCI trial than before, and the choice of agent favoured DOAC over warfarin. Almost half of patients were not on anticoagulants, a situation that requires further investigation, to ensure that AF patients are being optimally managed post-PCI.

Contexte: Des essais se sont penchés sur l'utilisation combinée d'anticoagulants oraux directs (AOD) et d'antiplaquettaires chez les patients atteints de fibrillation auriculaire (FA) qui subissent une intervention coronarienne percutanée (ICP). Il est possible que ces essais aient donné lieu à des modifications des habitudes de prescription. Méthodologie: Cet audit interne portant sur des Albertains atteints de FA subissant une ICP fournit une description des traitements antithrombotiques prescrits avant et après la publication des résultats de l'essai PIONEER AF-PCI (An O p en-label, Randomized, Controlled, Multicenter Study Explor i ng Tw o Treatme n t Strat e gi e s of R ivaroxaban and a Dose-Adjusted Oral Vitamin K Antagonist Treatment Strategy in Patients With A trial F ibrillation Who Undergo P ercutaneous C oronary I ntervention). Résultats: Les caractéristiques des cohortes étudiées avant (n = 597) et après (n = 708) la publication étaient semblables : âge médian, 72 ans; 23 % des femmes; 63 % ayant des antécédents de syndrome coronarien aigu; 22 % ayant des antécédents de saignements. Après la publication, on a observé une augmentation de 7,0 % (p = 0,01) de l'utilisation d'anticoagulants, dont une augmentation de 24,9 % de l'utilisation d'AOD et une diminution de 17,5 % de l'utilisation de warfarine (p < 0,0001). Une corrélation a été établie entre le recours aux AOD et l'appartenance à la cohorte prise en charge « après ¼ la publication des résultats de l'essai (rapport de cotes : 5,42; intervalle de confiance à 95 % : 3,75 ­ 7,82; p < 0,0001). Conclusions: Après la publication des résultats de l'essai PIONEER AF-PCI, les prescriptions d'anticoagulants ont sensiblement augmenté, et ce, en faveur des AOD plutôt que de la warfarine. Près de la moitié des patients ne prenaient pas d'anticoagulants, une situation qui nécessite un examen plus approfondi afin de s'assurer que les patients atteints de FA sont pris en charge de manière optimale après une ICP.

The Problem With Predictions: A Cautionary Tale of Empirically Adjusting Apixaban Dosing With Carbamazepine.

Concomitant use of apixaban and carbamazepine (CBZ) is not recommended due to an anticipated reduction in apixaban concentration, although few case reports describe this interaction. We report a case of initiating apixaban 10 mg twice daily (BID), in a patient stabilized on CBZ 600 mg BID that was guided by prior experience. Apixaban concentrations were substantially elevated with initial empiric dosing; apixaban dosing of 7.5 mg BID was eventually implemented. This case highlights the fact that the degree of induction by CBZ can vary, regardless of the dose, and requires clinicians to be cautious when applying prior experiences with patients to new patients.

L'utilisation concomitante de l'apixaban et de la carbamazépine (CBZ) n'est pas recommandée puisqu'on l'attribue à la réduction anticipée des concentrations de l'apixaban, bien que peu d'observations décrivent cette interaction. Nous présentons un cas sur l'amorce de l'apixaban (10 mg deux fois par jour [BID]) chez un patient stabilisé par CBZ, 600 mg BID (en fonction d'expériences antérieures). La posologie empirique initiale a fait substantiellement augmenter les concentrations d'apixaban; la posologie de l'apixaban de 7,5 mg BID a finalement été mise en place. Ce cas illustre le fait que le degré d'induction par CBZ peut varier, indépendamment de la dose, et obliger les cli-niciens à être prudents lorsqu'ils transposent leurs expériences antérieures aux nouveaux patients.

Practice patterns surrounding referral to a specialty venous thromboembolism (VTE) clinic: a retrospective review.

This study audited prescribing practices for patients with acute venous thromboembolism (VTE) prior to and after being seen in an outpatient VTE clinic. This retrospective chart review conducted between June 2018 through May 2019 included patients with confirmed acute VTE, seen for an initial appointment. Exclusion criteria were patients with additional indications for anticoagulation, lack of information to determine primary outcome and active cancer. To assess practices, the time taken to be seen in clinic, anticoagulant therapies (prior to/following clinic) used and concordance of anticoagulant use with product monographs were assessed. Of the 325 (40.6%) patients included, the median age was 57.7 years, most were referred with pulmonary embolism (PE) (54.5%) and the majority of referrals came through the emergency department (45.2%). The median time to be seen in clinic was 13 days, with no differences in time between type of VTE or proximity of clot. Prior to being seen in VTE clinic, most were prescribed direct oral anticoagulants (DOACs) (81.9%), with a small portion receiving low molecular weight heparin (LMWH) (12.9%) and warfarin (5.2%). Most received anticoagulants concordant with product monographs (87.7%), with more discordance with warfarin (52.9%) and LMWH (14.3%) compared to DOACs (9.4%) (P < 0.001). At the initial VTE clinic visit, 70 (21.5%) patients had therapy changes, with most being from LMWH/warfarin to a DOAC (47.1%). Our data reflects high uptake of DOACs for acute VTE treatment with most prescribed in accordance with product monographs.

A case series of the rifampin-warfarin drug interaction: focus on practical warfarin management.

PURPOSE: To provide practical guidance by providing weekly descriptions of warfarin requirements for the onset and offset of the rifampin-warfarin interaction. METHODS: A retrospective chart review within an outpatient Anticoagulation Clinic (AC). Patients were eligible for the onset phase provided they had known ambulatory-based warfarin steady-state requirements prior to rifampin initiation. For the offset phase, warfarin must be managed by the AC following rifampin discontinuation. Each phase was described separately with warfarin proportionate dose changes (median, IQR) for weeks 1, 2, and 4 as well as the change required to reach warfarin steady state. RESULTS: Ten patients with 11 courses of warfarin-rifampin were included. For onset, clinicians should anticipate proportionate warfarin dose increases of 30-80% from week 1 to week 2 and a further 20-100% from week 2 to 4, with an overall warfarin dose increase of 165% (IQR 99, 227) to reach steady state at 30 days. For offset, clinicians should anticipate proportionate warfarin dose decreases of 15-25% for both week 1 and 2, and a further 20% for both week 3 and 4, resulting in an overall warfarin decrease of 67% (IQR - 70, - 58) to reach steady state at 4 weeks for most patients. CONCLUSION: Close monitoring with at least twice weekly INRs for weeks 1 to 2 of both phases is needed to respond to substantially changing warfarin dose requirements. While inter- and intra-patient variability for proportionate warfarin dose changes for both the onset and offset of this drug interaction exists, our data provides general guidance.

Retrospective Review of Prescribing Patterns in Cancer-Associated Thrombosis: A Single Center Experience in Edmonton, Alberta, Canada.

Low molecular weight heparin (LMWH) is the standard of care for treating cancer-associated thrombosis (CAT), although new evidence for direct oral anticoagulants (DOACs) supports use in specific cancer populations. In this retrospective review at a specialty CAT clinic from 2016 to 2019, we report the use of anticoagulants (LMWH, DOACs, warfarin, anticoagulant class change) in the acute and chronic phases of CAT and compare use before/after publication of the Hokusai-VTE Cancer trial. Death, venous thromboembolism (VTE) recurrence and bleeding was also reported. Of the 221 included, median age was 69 years, with 57.5% having metastatic disease. In the acute phase, 80.1% were prescribed LMWH, 4.1% DOAC, and 14.5% had an anticoagulant class change (LMWH to DOAC; 78.1%). In the chronic phase, 35.8% were prescribed LMWH, 11.3% DOAC, and 42.9% had an anticoagulant class change (LMWH to DOAC; 90.1%). Use of DOACs in the acute and chronic phase prior to the Hokusai-VTE trial was 1.0% and 2.0%, respectively, and following publication was 6.8% and 19.6%. Death occurred for 22.6% patients, recurrent VTE in 7.2%, and bleeding in 5.0%. DOAC use is increasing with time; real-world data may help to guide optimization of the care of complex patients.

Carbamazepine Induction Impacting Apixaban Concentrations: A Case Report.

Avoidance of apixaban with carbamazepine (CBZ) is recommended owing to an anticipated reduction in apixaban concentration, although this drug interaction is poorly described. We report a case wherein apixaban concentration was measured before and 2 weeks after CBZ. Apixaban concentrations were substantially reduced; hence, the dose of apixaban was doubled alongside a small increase in CBZ. Subsequent apixaban concentrations were essentially unchanged. This extent of reduction in apixaban concentration appears to be related to the dose of CBZ, with the interaction occurring over 2-4 weeks. This combination should be avoided unless apixaban concentrations can be assessed using a calibrated assay.

Il est recommandé d'éviter l'administration concomitante d'apixaban et de carbamazépine (CBZ) puisqu'il peut en résulter une baisse de la concentration d'apixaban. L'interaction médicamenteuse en cause est toutefois insuffisamment caractérisée. Un cas est décrit où la concentration d'apixaban a été mesurée avant l'administration de CBZ et deux semaines plus tard. La concentration d'apixaban ayant diminué considérablement, la dose d'apixaban a été doublée parallèlement à une légère augmentation de la dose de CBZ. La concentration d'apixaban n'a essentiellement pas changé à la suite de cette modification posologique. L'ampleur de cette réduction de la concentration d'apixaban semble liée à la dose de CBZ, l'interaction se produisant sur une période de 2 à 4 semaines. L'association des deux médicaments doit être évitée à moins que la concentration d'apixaban puisse être évaluée au moyen d'une méthode étalonnée.

Clinical Pharmacist Services on Admission to a Large Correctional Center.

The clinical role of pharmacists in a correctional facility has not been fully described. We report the proportion of patients assessed by a pharmacist within 48 hours of admission to a large correctional facility. Of those assessed, the frequency and type of pharmacist interventions were described. A retrospective chart review was conducted for patients admitted to the Edmonton Remand Center (ERC) from September to November 2017. From 1,500 patients, 518 (34.5%) were assessed by a pharmacist, and 511 (98.6%) of those received one or more pharmacist interventions. Interventions were most commonly health care provider interactions (89.0%) and drug therapy interventions (76.1%). ERC pharmacists assessed a sizable proportion of admitted patients, with most receiving at least one pharmacist intervention.

Use of Direct Oral Anticoagulants Versus Traditional Therapies for Acute Venous Thromboembolism After Direct Discharge From the Emergency Department or After Hospitalization: An Audit of 16 Canadian Hospitals.

PURPOSE: This study compares and describes the use of direct oral anticoagulants (DOACs) versus traditional therapies (parenteral anticoagulant with or without warfarin) for acute venous thromboembolism (VTE) between individuals discharged directly from the emergency department (ED) versus those hospitalized. This study also reports patterns based on discharge from an academic, community, or rural-based site. METHODS: This retrospective medical records study included patients discharged with acute VTE (2015-2016) from 16 institutions across 4 provinces. Patients with atypical clots, other indications for anticoagulants, or an anticipated lifespan <3 months or those who were pregnant or breastfeeding were excluded. FINDINGS: Overall, 590 individuals (30.0%) discharged from the ED and 809 (53.8%) discharged after hospitalization were studied. Hospitalized patients were significantly older, had more comorbidities (cancer, pulmonary disease, and heart failure), and were more likely to have pulmonary embolism than deep vein thrombosis. DOAC use was significantly higher in the ED cohort versus the hospitalized cohort (51.4% vs 44.3%; P < 0.004) and more common for those having lower risk of pulmonary embolisms (simplified Pulmonary Embolism Severity Index score of 0 compared with ≥1) in the ED (58.0% and 26.5%; P < 0.0001) and hospitalized cohorts (57.1% and 35.7%; P < 0.0001). Use of DOACs was lowest in academic settings (46.2%) and highest in rural sites (56.7%). Follow-up patterns were different, with specialists and VTE clinics being most common in academic sites and family physicians being most common in rural practices. IMPLICATIONS: DOACs were used in less than half of all patients, with more use in EDs and rural sites. Follow-up patterns (VTE clinic or specialist vs family physician) varied and likely contributed to therapy selection. Over time, use of DOACs is likely to increase, and patient factors (eg, those younger with fewer comorbidities) and health care contact (eg, place of discharge or availability of an ambulatory VTE clinic) will likely continue to influence practice patterns.

Anticoagulant therapies and outcomes in obese patients with acute venous thromboembolism.

BACKGROUND: Direct oral anticoagulants (DOACs) are recommended in preference to traditional anticoagulants (LMWH ±â€¯warfarin) for treating acute venous thromboembolism (VTE). However, guidelines suggest avoiding DOACs in those >120 kg given limited data. OBJECTIVE: To capture outcome and prescription fill data in a cohort of patients >120 kg with acute VTE out to 1 year. METHODS: Using linked administrative data, a retrospective sub-study of obese patients (>120 kg) with acute VTE discharged from institutions from 2014 to 2017 was performed. Primarily, the overall rate of recurrent VTE was assessed. Secondarily, anticoagulant regimens (agent/dosing) and bleeding events were recorded with recurrent events confirmed by chart reviews. Outcomes were compared between DOACs and traditional therapies. RESULTS: Amongst 187 patients included, the overall rate of recurrent VTE out to 1 year was 0.006 events/patient year, and the only event during the entire follow-up occurred off therapy. Throughout the year, 38.5% were prescribed a DOAC only, 32.6% were prescribed traditional therapy only and 23.5% were switched from LMWH/warfarin to a DOAC. The proportion of patients receiving sub-therapeutic, standard or supra-therapeutic regimens were: DOAC (11.1%, 85.2%, 3.7%), LMWH (24.2%, 71.0%, 4.8%), warfarin (30.4%, 55.0%, 15.0%). Bleeding occurred in 9 (8.3%) and 9 (11.5%) patients on DOAC and traditional therapy, respectively (relative risk 0.85 [95%CI 0.44-1.28]). CONCLUSIONS: More obese patients with acute VTE were prescribed DOACs than traditional therapies. Standard dosing was used for DOACs (85.2%), whereas sub-optimal dosing occurred for 25-33% receiving traditional therapies. Rates of recurrent VTE and bleeding were similar in the two groups, lending support for DOAC use in this population.

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.

Warfarin Reinitiation After Intracranial Hemorrhage: A Case Series of Heart Valve Patients.

Patients with mechanical heart valves are at high thrombotic risk and require warfarin. Among those developing intracranial hemorrhage, limited data are available to guide clinicians with antithrombotic reinitiation. This 13-patient case series of warfarin-associated intracranial hemorrhages found the time to reinitiate antithrombotic therapy (17 days, interquartile range 21.5 days), and changes to international normalized ratio targets were variable and neither correlated with the type, location, or etiology of bleed, nor the valve and associated thromboembolic risk. The initial presentation significantly impacted prognosis, and diligent assessment and follow-up may support positive long-term outcomes.