Development and Application of an Attribute-Based Taxonomy on the Benefits of Oral Anticoagulant Switching in Atrial Fibrillation: A Delphi Study.

INTRODUCTION: Patients with atrial fibrillation (AF) often switch between oral anticoagulants (OACs). It can be hard to know why a patient has switched outside of a clinical setting. Medication attribute comparisons can suggest benefits. Consensus on terms and definitions is required for inferring OAC switch benefits. The objectives of the study were to generate consensus on a taxonomy of the potential benefits of OAC switching in patients with AF and apply the taxonomy to real-world data. METHODS: Nine expert clinicians (seven clinical pharmacists, two cardiologists) with at least 3 years of clinical and research experience in AF participated in a Delphi process. The experts rated and commented on a proposed taxonomy on the potential benefits of OAC switching. After each Delphi round, ratings were analyzed with the RAND Corporation/University of California, Los Angeles (RAND/UCLA) appropriateness method. Median ratings, disagreement index, and comments were used to modify the taxonomy. The resulting taxonomy from the Delphi process was applied to a cohort of patients with AF who switched OACs in a population-based administrative health dataset from 1996 to 2019 in British Columbia, Canada. RESULTS: The taxonomy was finalized in two Delphi rounds, reaching consensus on five switch benefit categories: safety, effectiveness, convenience, economic considerations, and drug interactions. Safety benefit (a switch that could lower the risk of adverse drug events) had three subcategories: major bleeding, intracranial hemorrhage (ICH), and gastrointestinal (GI) bleeding. Effectiveness benefit had four subcategories: stroke and systemic embolism (SSE), ischemic stroke, myocardial infarction (MI), and all-cause mortality. Real-world OAC switches revealed that more OAC switches had convenience (72.6%) and drug interaction (63.0%) benefits compared to effectiveness (SSE 22.0%, ischemic stroke 11.1%, MI 3.1%, all-cause mortality 10.1%), safety (major bleeding 24.3%, GI bleeding 10.6%, ICH 48.5%), and economic benefits (12.1%). CONCLUSIONS: The Delphi-based taxonomy identified five criteria for the beneficial effects of OAC switching, aiding in characterizing real-world OAC switching.

Management of Tachycardia-Mediated Cardiomyopathy: Experience from the Vancouver General Hospital Cardiac Function Clinic (TMC-EXPLOR Study).

Background: Tachycardia-mediated cardiomyopathy (TMC) is a reversible form of heart failure with reduced ejection fraction (HFrEF), most commonly caused by atrial fibrillation or atrial flutter. Evidence for its management is scarce, and practice patterns are highly variable. Objective: To describe management patterns for HFrEF and atrial arrhythmias in patients with TMC at a specialty heart failure clinic. Methods: This retrospective cohort study involved adults with HFrEF and a physician-determined diagnosis of TMC, with an initial visit for this problem between October 2018 and October 2019. The 2 primary outcomes, evaluated at 1 year after the initial visit, were the proportion of patients receiving triple therapy (combination of angiotensin receptor-neprilysin inhibitor [or angiotensin-converting enzyme inhibitor/angiotensin II receptor blocker if ejection fraction improved to > 40% by 1 year], ß-blocker, and mineralocorticoid receptor antagonist at any dose) and the proportion receiving or with a plan to receive rhythm control. Results: A total of 59 participants met the inclusion criteria. The mean age was 73 years, 39 patients (66%) were male, and 42 (71%) had hypertension. At 1-year follow-up, 42 (71%) were receiving triple therapy, and rhythm control was attempted or planned for 20 (34%). Among the 17 patients (29%) not receiving triple therapy, a mineralocorticoid receptor antagonist was the agent most commonly omitted. Conclusions: In a specialty heart failure clinic, most patients with TMC were receiving triple therapy, with a mineralocorticoid receptor antagonist being the agent most commonly missing among those not receiving triple therapy. One-third of patients with TMC had received a rhythm-control strategy. These gaps in HFrEF therapy and rhythm control represent key areas for quality improvement initiatives in the management of patients with TMC.

Contexte: La cardiomyopathie rythmique (CMR) est une forme réversible d'insuffisance cardiaque à fraction d'éjection réduite (HFrEF), le plus souvent causée par la fibrillation auriculaire ou le flutter auriculaire. Les données probantes relatives à sa prise en charge sont rares et les modèles de pratique sont très variables. Objectif: Décrire les schémas de prise en charge de l'HFrEF et des arythmies auriculaires chez les patients atteints d'une CMR dans une clinique spécialisée en insuffisance cardiaque. Méthodes: Cette étude de cohorte rétrospective impliquait des adultes atteints d'HFrEF et ayant reçu un diagnostic de CMR déterminé par un médecin, avec une première visite pour ce problème de santé entre octobre 2018 et octobre 2019. Les 2 résultats principaux, évalués 1 an après la première visite, étaient les suivants: 1) la proportion de patients recevant une trithérapie (association récepteur de l'angiotensine-néprilysine (ARNi) [ou inhibiteur de l'enzyme de conversion de l'angiotensine/antagoniste des récepteurs de l'angiotensine II si la fraction d'éjection s'est améliorée à > 40 % à 1 an], un traitement par ß-bloquant et un antagoniste des récepteurs des minéralocorticoïdes à n'importe quelle dose); et 2) la proportion recevant ou prévoyant de recevoir un médicament antiarythmique. Résultats: Au total, 59 participants répondaient aux critères d'inclusion. L'âge moyen était de 73 ans; 39 patients (66 %) étaient des hommes et 42 (71 %) avaient de l'hypertension. Au marqueur d'un an, 42 (71 %) recevaient une trithérapie et un médicament antiarythmique a été tenté ou était prévu pour 20 (34 %) patients. Parmi les 17 patients (29 %) ne recevant pas de trithérapie, l'agent le plus souvent omis était l'antagoniste des récepteurs des minéralocorticoïdes. Conclusions: Dans une clinique spécialisée dans l'insuffisance cardiaque, la plupart des patients atteints d'une CMR recevaient une trithérapie, l'antagoniste des récepteurs minéralocorticoïdes étant l'agent le plus souvent absent chez ceux qui n'en recevaient pas. Un tiers des patients atteints d'une CMR avaient reçu un médicament antiarythmique. Ces lacunes concernant la thérapie HFrEF et la gestion de l'arythmie représentent des domaines clés pour les initiatives d'amélioration de la qualité dans la prise en charge des patients atteints d'une CMR.

Oral anticoagulant adherence and switching in patients with atrial fibrillation: A prospective observational study.

BACKGROUND: Adherence to oral anticoagulants (OACs) in patients with atrial fibrillation (AF) is important in preventing stroke. The dominance of retrospective studies using administrative data has led to a lack of data on psychosocial determinants of adherence and prevented comparison of adherence between OAC drug classes. OAC switching is another aspect of adherence that is unexplored. METHODS: A prospective design was utilized to measure AF patients' self-reported adherence and OAC switching, and to identify their clinical, demographic, and psychosocial determinants. Participants were recruited from specialized AF clinics in Canada and followed for up to 2 years. Data were collected via telephone every 3-4 months using a structured survey. Adherence was measured using the Morisky Medication Adherence scale (©MMAS-8). RESULTS: The included participants (N = 306) were followed for a median follow up time of 14.1 months and had an average of 3.2(SD 1.4) study visits. The mean self-reported adherence on the ©MMAS-8 was 7.28(SD 0.71) for patients receiving care at specialized AF clinics. Older age, experiencing a bleed, and higher satisfaction with the burden of medications were significantly associated with higher adherence. Drug class did not have any significant impact on adherence. 7.8% of the cohort experienced a switch with most of them being from warfarin to DOAC. Taking warfarin as the index medication, experiencing a bleed and older age were significantly associated with higher odds of switching. CONCLUSION: Patients with AF reported high adherence to their OAC therapy however being on DOAC may not translate to better adherence compared to VKA. Improving satisfaction with the burden of therapy is important in improving adherence.

Satisfaction With Oral Anticoagulants Among Patients With Atrial Fibrillation: A Prospective Observational Study.

BACKGROUND: Satisfaction with treatment has been identified as an important contributing factor to adherence with oral anticoagulant (OAC) therapy in patients with atrial fibrillation (AF). We aimed to evaluate the satisfaction level of patients with AF regarding OAC use over time, using validated patient-reported outcome instruments, and to identify associated patient characteristics. METHODS: Participants were recruited from specialized AF clinics in Canada. Eligible AF patients who were prescribed OACs were followed for up to 2 years. Participants were interviewed via telephone every 3-4 months using a structured survey. The Treatment Satisfaction Questionnaire for Medication (TSQM II) and the Anti-Clot Treatment Scale (ACTS) were used to measure satisfaction over time. RESULTS: Among the 306 participants, satisfaction scores on the TSQM II and ACTS instruments were high. Unadjusted analyses showed significantly greater satisfaction with the burden of therapy with direct OACs (DOACs) compared to that with warfarin (small-magnitude effect) and greater satisfaction with the convenience of rivaroxaban, compared with that of all other OACs (moderate-magnitude effect). After adjustment for all other variables, vitamin K antagonist therapy was associated with greater global satisfaction than was DOAC treatment. Satisfaction with benefit and burden as measured by the ACTS scale, and global satisfaction on the TSQM II scale, tended to increase over time. Patient factors that were somewhat consistently associated with greater satisfaction were female sex and younger age. CONCLUSIONS: Patients with AF were highly satisfied with their therapy, with few differences among OAC classes and individual OACs. Individual patients may or may not be more satisfied with DOAC than VKA therapy, and regardless of the OAC prescribed, the may require significant support to maintain therapy adherence.

CONTEXTE: La satisfaction à l'égard du traitement a été désignée comme un facteur important contribuant à l'adhésion au traitement par anticoagulants oraux (ACO) chez les patients atteints de fibrillation auriculaire (FA). Notre objectif était d'évaluer le degré de satisfaction des patients atteints de FA concernant l'utilisation des ACO au fil du temps, à l'aide d'instruments validés mesurant les résultats signalés par les patients, et de déterminer les caractéristiques connexes des patients. MÉTHODOLOGIE: Les participants ont été recrutés dans des cliniques spécialisées en FA au Canada. Les patients admissibles atteints de FA qui se sont fait prescrire des ACO ont été suivis pendant une période allant jusqu'à 2 ans. Les participants ont été interrogés par téléphone tous les 3 ou 4 mois à l'aide d'une enquête structurée. Le questionnaire Treatment Satisfaction Questionnaire for Medication ­ Version II (TSQM II) et l'échelle Anti-Clot Treatment Scale (ACTS) ont été utilisés pour mesurer la satisfaction au fil du temps. RÉSULTATS: Parmi les 306 participants, les taux de satisfaction indiqués par les instruments TSQM II et ACTS étaient élevés. Les analyses non corrigées ont montré une satisfaction liée au fardeau du traitement significativement plus élevée avec les ACO directs qu'avec la warfarine (effet de faible ampleur) et une plus grande satisfaction concernant la commodité du rivaroxaban par rapport à celle de tous les autres ACO (effet de moyenne ampleur). Après ajustement pour tenir compte de toutes les autres variables, le traitement par antivitamines K (AVK) était associé à une plus grande satisfaction globale que le traitement par ACO direct. La satisfaction à l'égard des avantages et du fardeau, mesurée par l'échelle ACTS, et la satisfaction globale sur l'échelle TSQM II, ont eu tendance à augmenter avec le temps. Les facteurs liés aux patients qui ont été associés de manière assez constante à une plus grande satisfaction étaient le sexe féminin et un âge plus jeune. CONCLUSIONS: Les patients atteints de FA étaient très satisfaits de leur traitement, et peu de différences existaient entre les classes d'ACO et les ACO individuels. Chaque patient peut être ou non plus satisfait du traitement par ACO direct que par AVK et, quel que soit l'ACO prescrit, il peut avoir besoin d'un soutien important pour maintenir l'adhésion au traitement.

Effectiveness of a simple medication adjustment protocol for optimizing peri-cardioversion rate control: A derivation and validation cohort study.

BACKGROUND: Rate control medications are foundational in the management of persistent atrial fibrillation (AF). There are no guidelines for adjusting these medications prior to elective direct-current cardioversion (DCCV). OBJECTIVE: To derive and validate a preprocedural medication adjustment protocol that maintains peri-DCCV rate control and minimizes risk of postconversion bradycardia, pauses, need for pacing, and cardiopulmonary resuscitation (CPR). METHODS: Consecutive patients with persistent AF awaiting elective DCCV across 2 hospitals were screened for inclusion into derivation, validation, and control cohorts. In the derivation cohort, each patient taking an atrioventricular (AV) nodal blocker had medications adjusted based on heart rate (HR) 2 days before DCCV, and the magnitude of dose adjustment was compared with peri-DCCV HR. The adjustment protocol that achieved the highest percentage of optimal peri-DCCV rate control was tested prospectively in the validation cohort and compared to a standard-of-care control group. RESULTS: The optimal protocol from the derivation cohort (n = 71), based on the 2-day pre-DCCV HR, was to (1) CONTINUE AV nodal blocker for HR ≥ 100 beats per minute (bpm), (2) reduce dose by ONE increment when 80-99 bpm, (3) reduce dose by TWO increments when 60-79 bpm, and (4) HOLD when <60 bpm. In the prospective validation cohort (n = 106), this protocol improved peri-DCCV rate control (82% vs 62%, P < .001) compared to current standard of care (n = 107). There were no conversion pauses ≥5 seconds, need for pacing, or CPR post-DCCV. CONCLUSION: This simple preprocedural medication adjustment protocol provides an effective strategy of optimizing peri-DCCV rate control in patients with AF.

Chronic Amiodarone Use and the Risk of Cancer: A Systematic Review and Meta-analysis.

BACKGROUND: Observational studies have identified inconsistent associations between chronic use of amiodarone and cancer-related outcomes. We performed a systematic review and meta-analysis to evaluate cancer risk among patients receiving amiodarone. METHODS: We searched MEDLINE, Embase, and the Cochrane Central Register of Controlled Trials (CENTRAL) to May 1, 2020. We included randomized controlled trials (RCTs) with follow-up ≥2 years that compared amiodarone (any dose) to any comparator (placebo, active pharmacologic or interventional comparator, or usual care), and reported ≥1 outcome of interest. We contacted authors of published chronic amiodarone trials for potentially unreported cancer outcomes. The primary outcome was cancer incidence. Secondary outcomes were cancer-related death and site-specific cancers. We determined risk ratios and 95% confidence intervals using a fixed-effect model, and statistical heterogeneity using I 2. We conducted prespecified subgroup and sensitivity analyses for amiodarone indication, amiodarone dose, duration of therapy, and trial-level risk of bias. RESULTS: From 1439 articles, we included 5 RCTs (n = 4357). Mean follow-up duration ranged from 21 to 37 months. We included previously unpublished cancer outcome data from 1 RCT. Our primary outcome was not reported in any RCT. There was no significant difference in cancer-related death between amiodarone (1.69%) and the comparator (1.75%) (risk ratio 0.96, 95% confidence interval 0.57-1.63; I 2 = 0%). There were no significant interactions from our subgroup or sensitivity analyses. CONCLUSIONS: Chronic amiodarone use did not increase cancer-related deaths. Data from RCTs do not support an increased risk of cancer-related harms with amiodarone use, and these concerns should not deter use of amiodarone when indicated.

CONTEXTE: Des études d'observation ont révélé des associations incohérentes entre l'usage à long terme de l'amiodarone et les issues liées au cancer. Nous avons mené une revue systématique et une méta-analyse pour évaluer le risque de cancer chez les patients qui reçoivent l'amiodarone. MÉTHODOLOGIE: Nous avons épluché les registres MEDLINE, Embase et Cochrane Central Register of Controlled Trials (CENTRAL) jusqu'au 1er mai 2020. Nous avons retenu les essais contrôlés randomisés (ECR) comportant une période de suivi d'au moins 2 ans qui visaient à comparer l'amiodarone (toutes les doses) à un agent (placebo, agent de comparaison pharmacologique ou interventionnel actif, ou traitement standard) et qui ont rapporté au moins un résultat d'intérêt. Nous avons communiqué avec les auteurs de publications d'essais sur l'emploi à long terme de l'amiodarone dans le but de déceler des issues possibles de cancer non signalées. Le principal critère d'évaluation était la fréquence du cancer. Les critères d'évaluation secondaires étaient les décès liés au cancer et les cancers en fonction de leur localisation. Nous avons établi les rapports de risques et les intervalles de confiance à 95 % au moyen d'un modèle à effets fixes et d'une hétérogénéité statistique quantifiée à l'aide d'une I 2. Nous avons réalisé des analyses par sous-groupes et des analyses de sensibilité prédéfinies pour l'indication de l'amiodarone, la dose d'amiodarone, la durée du traitement et le risque de biais à l'échelle des essais. RÉSULTATS: À partir de 1 439 articles, nous avons retenu 5 études contrôlées à répartition aléatoire (n = 4 357). La durée de suivi moyenne variait de 21 à 37 mois. Nous avons inclus des données d'un ECR portant sur l'issue de cancer qui n'avaient pas été publiées auparavant. Notre principal critère d'évaluation n'a fait l'objet d'aucun rapport dans les ECR. En ce qui concerne les décès liés au cancer, aucune différence n'a été observée entre l'amiodarone (1,69 %) et l'agent de comparaison (1,75 %) (rapport des risques de 0,96; intervalle de confiance à 95 % de 0,57 à 1,63; I 2 = 0 %). Aucune interaction notable n'est ressortie de nos analyses par sous-groupe ou de nos analyses de sensibilité. CONCLUSIONS: L'administration à long terme d'amiodarone n'a pas augmenté le taux de décès liés au cancer. Selon les données des ECR, l'emploi de l'amiodarone n'est pas associé à une augmentation du risque de cancer, et les craintes à cet égard ne devraient pas dissuader d'utiliser l'amiodarone lorsqu'elle est indiquée.

Evaluating the Effect of a Patient Decision Aid for Atrial Fibrillation Stroke Prevention Therapy.

BACKGROUND: Stroke prevention therapy decisions for patients with atrial fibrillation (AF) are complex and require trade-offs, but few validated patient decision aids (PDAs) are available to facilitate shared decision making. OBJECTIVE: To evaluate the effects of a novel PDA on decision-making parameters for AF patients choosing stroke prevention therapy. METHODS: We developed an evidence-based individualized online AF PDA for stroke prevention therapy and evaluated it in a prospective observational pilot study. The primary outcome was decisional conflict. Secondary outcomes were knowledge, usability/acceptability, patient preferences, effects on therapy choices, and participant feedback. RESULTS: 37 participants completed the PDA. The PDA could be completed independently and was well accepted. It significantly decreased the mean decisional conflict score ( P < 0.001) and all its subscales and increased participant AF knowledge ( P = 0.02). 76% of participants indicated that their individualized therapy attribute ranking was congruent with their values. The PDA-generated best-match therapy was chosen by 70% of participants in decision 1 (no therapy, aspirin, or oral anticoagulant), and 17% for decision 2 (choice of anticoagulant). Among AF patients, 60% chose a different drug than that currently prescribed to them. Conclusion and Relevance: Our PDA was effective for reducing decisional conflict, increasing patient knowledge, eliciting patients' values, and presenting therapy options that aligned with patients' values and preferences. Using the PDA revealed that many patients have therapy preferences different from their currently prescribed treatment. The PDA is a practical and potentially valuable tool to facilitate decision making about stroke prevention therapy for AF.

Assessment of atrial fibrillation patients' education needs from patient and clinician perspectives: A qualitative descriptive study.

INTRODUCTION: Patients' lack of knowledge is a key barrier to therapy adherence. We aimed to gather insights into atrial fibrillation (AF) patients' education needs from patient and clinician viewpoints. METHODS: We conducted a qualitative descriptive study using purposive sampling and semi-structured interviews with AF patients and clinicians recruited from AF clinics. Data from patients and clinicians were analyzed independently and iteratively through inductive qualitative thematic analysis. RESULTS: Eleven clinicians and 10 patients were interviewed. Three themes emerged from analysis of clinician data: (1) patients' knowledge gaps and misconceptions, (2) clinicians' experiences teaching AF patients, and (3) clinicians' suggestions for AF education programs. Four themes emerged from the patient data: (1) emotional appraisal of the disease, (2) information seeking behavior, (3) knowledge gaps, and (4) education preferences. A key finding was identification of the need for education that addresses patients' unjustified anxieties by emphasizing that AF is not fatal, and that many patients with AF live a normal life. Risk communication was identified as the most challenging aspect of AF education. In synthesizing our findings, we developed evidence-based recommendations for educational strategies for AF. CONCLUSION: We found that AF patients have many knowledge gaps and misconceptions, significant emotional education needs, and a positive attitude towards online and classroom education. In synthesizing our findings, we developed evidence-based recommendations which can inform the design of AF patient education programs and initiatives.

Clinical effectiveness of a systematic "pill-in-the-pocket" approach for the management of paroxysmal atrial fibrillation.

BACKGROUND: For patients with symptomatic, sustained atrial fibrillation (AF), a "pill-in-the-pocket" antiarrhythmic drug (PIP-AAD) strategy has been proposed to reduce emergency department (ED) use. OBJECTIVE: To assess the clinical utility of a protocolled PIP-AAD approach within contemporary practice. METHODS: Consecutive patients who hemodynamically tolerated symptomatic, sustained AF were prospectively managed with the PIP-AAD strategy. All patients were given an atrioventricular nodal blocker 30 minutes prior to a single oral dose of a class Ic antiarrhythmic drug. If the initial PIP-AAD in the ED was efficacious and tolerated, PIP-AADs were given out of hospital for subsequent sustained AF episodes. Usage and complications were systematically recorded. RESULTS: During a median follow-up period of 565 days, 43 of 80 patients presented to the ED for initial PIP-AAD. Sinus rhythm was restored without complication in 30 of 43 patients. The reasons for initial PIP-AAD failure were inefficacy (6 patients), significant hypotension (4 patients), conversion to flutter necessitating cardioversion (2 patients), and syncopal conversion pause (1 patient). For the 30 patients with successful initial PIP-AAD, 159 out-of-hospital PIP-AAD treatments occurred (mean 5.3 ± SD 1.3 per patient). Compared with ED visits in the period prior to PIP-AAD initiation, there was a significant reduction in visits (2.6 ± 3.0 vs. 0.4±0.9 ED visits per patient, P < .001) and the need for cardioversion (2.3 ± 3.1 vs. 0.0 ± 0.2 treatments per patient, P < .001). Adverse events associated with out-of-hospital PIP-AAD include presyncope (3 of 30 patients), syncope necessitating pacemaker implantation (1 patient), and conversion to flutter (1 patient). CONCLUSION: Out-of-hospital PIP-AAD can be an effective for highly selected patients; however, the rates of treatment failure and adverse events are clinically relevant, which limits the widespread application of a PIP-AAD approach.