Effectiveness and safety of oral anticoagulants in older patients with atrial fibrillation : a systematic review and meta-analysis

Background and Objective: Atrial fibrillation (AF), the most common cardiac arrhythmia, typically increases with age. Oral anticoagulants (OACs) are the cornerstone of treatment to reduce the associated risk for systemic thromboembolism. Four large randomized controlled trials (RCTs) have shown that non-vitamin K antagonist oral anticoagulants (NOACs) are non-inferior to vitamin K antagonists (VKAs) in preventing stroke and systemic embolism, as well as regarding their risk for major bleeding. However, as vulnerable geriatric patients with AF were largely underrepresented in these trials, physicians are faced with the challenge of choosing the right anticoagulant for geriatric patients in real-life clinical practice. In this vulnerable patient group, NOACs tend to be underused or underdosed due to concerns of excessive fall-related intracranial bleeding, cognitive impairment, multiple drug-drug interactions, low body weight or impaired renal function. As life expectancy continues to rise worldwide, the number of geriatric patients substantially increases. Therefore, there is an urgent need for a critical appraisal of the added value of NOACs in geriatric patients with AF at high thromboembolic and bleeding risk. Methods and Results: This systematic review provides an overview of the literature on the impact of increased age (≥75 years), multimorbidity, polypharmacy, increased falling risk, frailty and dementia on the effectiveness and safety of NOACs as compared to VKAs, after searching the Medline database. Moreover, a meta-analysis on the impact of increased age ≥75 years old was performed after pooling results from 6 post hoc analyses of RCTs and 6 longitudinal observational cohort studies, highlighting the superior effectiveness (hazard ratio (HR) 0.83, 95% confidence interval (CI) [0.74–0.94] for stroke/SE; HR 0.77, 95%CI [0.65–0.92] for mortality) and non-inferior safety (HR 0.93, 95%CI [0.86–1.01] for major bleeding; HR 0.58, 95%CI [0.50–0.67] for intracranial bleeding; HR 1.17, 95%CI [0.99–1.38] for gastrointestinal bleeding) of NOACs versus VKAs in older AF patients. Conclusion: Across geriatric subgroups, apixaban was consistently associated with the most favourable benefit-risk profile and should therefore be preferred in geriatric patients with AF. However, research gaps on the impact of increased falling risk, frailty and baseline dementia were identified, requiring careful consideration while awaiting more results

Long-term comparative effectiveness and safety of dabigatran, rivaroxaban, apixaban and edoxaban in patients with atrial fibrillation:A nationwide cohort study

Background: Although non-vitamin K antagonist oral anticoagulants (NOACs) are recommended over vitamin K antagonists (VKAs) in atrial fibrillation (AF) management, direct long-term head-to-head comparisons are lacking. Therefore, their risk-benefit profiles were investigated compared to VKAs and between NOACs. Methods: AF patients initiating anticoagulation between 2013–2019 were identified in Belgian nationwide data. Inverse probability of treatment weighted Cox regression was used to investigate effectiveness and safety outcomes and were additionally stratified by NOAC dose. Results: Among 254,478 AF patients (328,796 person-years of follow-up), NOACs were associated with significantly lower risks of stroke or systemic embolism (stroke/SE) (hazard ratio (HR) 0.68, 95% confidence interval (CI) (0.64–0.72)), all-cause mortality (HR 0.76, 95%CI (0.74–0.79)), major or clinically relevant non-major bleeding (MB/CRNMB) (HR 0.94, 95%CI (0.91–0.98)) and intracranial hemorrhage (HR 0.73, 95%CI (0.66–0.79)), but non-significantly different risks of myocardial infarction, gastrointestinal and urogenital bleeding compared to VKAs. Despite similar stroke/SE risks, dabigatran and apixaban were associated with significantly lower MB/CRNMB risks compared to rivaroxaban (HR 0.86, 95%CI (0.83–0.90); HR 0.86, 95%CI (0.83–0.89), respectively) and edoxaban (HR 0.91, 95%CI (0.83–0.99); HR 0.86, 95%CI (0.81–0.91), respectively), and apixaban with significantly lower major bleeding risks compared to dabigatran (HR 0.86, 95%CI (0.80–0.92)) and edoxaban (HR 0.79, 95%CI (0.72–0.86)). However, higher mortality risks were observed in some risk groups including with apixaban in patients with diabetes or concomitantly using digoxin compared to dabigatran and edoxaban, respectively. Conclusion: NOACs had better long-term risk-benefit profiles than VKAs. While effectiveness was comparable, apixaban was overall associated with a more favorable safety profile followed by dabigatran

Key elements in the quality assessment of a type 3 medication review

Background: Medication reviews are a structured evaluation of a patient’s pharmacotherapy with the aim of optimizing medicines use and improving health outcomes. This entails detecting drug related problems and recommending interventions. A high level of quality is essential for the successful implementation of this service in community pharmacies but currently there is no instrument or tool to assess that overall quality.Aim: This study investigated the development of quality criteria of type 3 medication reviews (MR3s).Methods: After surveying the literature, an electronic questionnaire was developed to gather information about quality criteria for MR3. This survey, in Dutch, was distributed electronically. Four groups were queried: 1) pharmacists, mainly working in the Netherlands, involved in practice research and contacted through the PRISMA (Practice Research In Collaboration With Pharmacists) foundation, 2) Belgian pharmacy academics and pharmacists active in professional associations (APA), 3) Belgian pharmacists trained in medication review (MR) by the Royal Pharmacists Association of Antwerp (KAVA) and 4) Belgian pharmacy students. The survey included 57 criteria, divided into eight domains, which were ranked according to their importance by the participants. The results were analyzed statistically using the nonparametric Kruskal–Wallis test.Results: The survey was completed by 95 participants, including 42 PRISMA pharmacists, 19 APA pharmacists, 18 KAVA pharmacists and 16 pharmacy students. Opinions from participants from the different groups overlapped significantly. The use of simple and understandable language in the conversation with the patient was considered essential by the majority. Discussing the usefulness and purpose of a MR3 with the patient was also rated highly by all groups. Differences of opinion were present in aspects about laboratory values, the use of specific tools, and reporting to and consultation with the treating physician. The participants themselves formulated a limited number of additional assessment criteria.Conclusion: There was widespread agreement on the hierarchy of the quality assessment criteria for MR3s. Minor differences were related to the experience of the participants. With these results and a small number of suggested extra criteria, a quality assessment instrument for MR3 can be created

Appropriateness of DOAC Prescribing Before and During Hospital Admission and Analysis of Determinants for Inappropriate Prescribing

Background and Objectives: Appropriate dosing of direct oral anticoagulants (DOACs) is required to avoid under- and overdosing that may precipitate strokes or thromboembolic events and bleedings, respectively. Our objective was to analyze the appropriateness of DOAC dosing according to the summaries of product characteristics (SmPC). Furthermore, determinants for inappropriate prescribing were investigated.Methodology: Retrospective cohort study of hospitalized patients aged ≥60 years with at least one DOAC intake during hospital stay. Descriptive analyses were used to summarize the characteristics of the study population. Chi-square test was used to evaluate differences between DOACs. Binary logistic regression analysis was performed to assess determinants for inappropriate prescribing.Results: For the 772 included patients, inappropriate dosing occurred in 25.0% of hospitalizations with 23.4, 21.9, and 29.7% for dabigatran, rivaroxaban, and apixaban, respectively (p = 0.084). Underdosing was most prevalent for apixaban (24.5%) compared to dabigatran (14.0%) and rivaroxaban (12.8%), p < 0.001. In 67.1% (apixaban), 26.7% (dabigatran), and 51.2% (rivaroxaban) of underdosed DOAC cases according to the SmPC, the dose would be considered appropriate according to the European Heart Rhytm Association (EHRA) guidelines. Overdosing was observed in 4.5% (apixaban), 4.7% (dabigatran), and 7.7% (rivaroxaban) of patients. For all DOACs, our analysis showed an age ≥80 years (p = 0.036), use of apixaban (p = 0.026), DOAC use before hospitalization (p = 0.001), intermediate renal function (p = 0.014), and use of narcotic analgesics (p = 0.019) to be associated with a higher rate of inappropriate prescribing. Undergoing surgery was associated with a lower odds of inappropriate prescribing (p = 0.012). For rivaroxaban, use of medication for hypothyroidism (p = 0.027) and the reduced dose (p < 0.001) were determinants for inappropriate prescribing. Treatment of venous thromboembolism was associated with less errors (p = 0.002). For apixaban, severe renal insufficiency (p < 0.001) and initiation in hospital (p = 0.016) were associated with less and the reduced dose (p < 0.001) with more inappropriate prescribing. No determinants were found in the dabigatran subgroup.Conclusions: Inappropriate DOAC prescribing is frequent with underdosing being the most common drug related problem when using the SmPC as reference. More appropriate prescriptions were found when taking the EHRA guidelines into account. Analysis of determinants of inappropriate prescribing yielded insights in the risk factors associated with inappropriate DOAC prescriptions

Impact of a single non-sex-related stroke risk factor on atrial fibrillation and oral anticoagulant outcomes: A systematic review and meta-analysis

Aims Oral anticoagulants (OACs) are crucial for treating atrial fibrillation (AF) patients at high thromboembolic risk. However, in AF patients at intermediate thromboembolic risk with a single non-sex-related stroke risk factor (CHA 2 D

Pharmacists’ confidence when providing pharmaceutical care on anticoagulants, a multinational survey

Background: Guidelines on the management of orally anticoagulated patients are continuously evolving, leading to an increased need for pharmacists to be fully integrated in care provision.Objective: To identify self-reported gaps in confidence among practicing pharmacists in the area of anticoagulation. Setting Pharmacists in different work settings in different countries.Method: Cross-sectional international survey from October 2015 till November 2016 among pharmacists working in different settings to assess their level of confidence when delivering anticoagulants as well as to identify possible educational needs regarding this medication class. Validation of the survey was ensured.Results: Responses from 4212 pharmacists originating from 18 countries were obtained. Pharmacists’ level of confidence was significantly higher (p < 0.001) when advising patients on vitamin K antagonists (VKAs) versus non-vitamin K antagonists (NOACs). In general, hospital pharmacists displayed higher confidence levels compared to community pharmacists when advising patients on anticoagulation (p < 0.001). Two distinct patterns of confidence levels emerged relating to basic and advanced pharmaceutical care. Confidence levels when providing advanced pharmaceutical care were significantly higher for Oceania and lower for South America (p < 0.005).Conclusions: Pharmacists felt more confident in supporting patients receiving VKAs compared to the more recently introduced NOACs. With the increasing use of NOACs and the risks pertaining to anticoagulation therapy, it is essential to invest in education for pharmacists to address their knowledge gaps enabling them to confidently support patients receiving oral anticoagulants.The project was funded by the Davie-Ratnoff-Macfarlane (DRM) foundation.info:eu-repo/semantics/publishedVersio

Pharmacists' confidence when providing pharmaceutical care on anticoagulants, a multinational survey

Background Guidelines on the management of orally anticoagulated patients are continuously evolving, leading to an increased need for pharmacists to be fully integrated in care provision. Objective To identify self-reported gaps in confidence among practicing pharmacists in the area of anticoagulation. Setting Pharmacists in different work settings in different countries. Method Cross-sectional international survey from October 2015 till November 2016 among pharmacists working in different settings to assess their level of confidence when delivering anticoagulants as well as to identify possible educational needs regarding this medication class. Validation of the survey was ensured. Results Responses from 4212 pharmacists originating from 18 countries were obtained. Pharmacists' level of confidence was significantly higher (p < 0.001) when advising patients on vitamin K antagonists (VKAs) versus non-vitamin K antagonists (NOACs). In general, hospital pharmacists displayed higher confidence levels compared to community pharmacists when advising patients on anticoagulation (p < 0.001). Two distinct patterns of confidence levels emerged relating to basic and advanced pharmaceutical care. Confidence levels when providing advanced pharmaceutical care were significantly higher for Oceania and lower for South America (p < 0.005). Conclusions Pharmacists felt more confident in supporting patients receiving VKAs compared to the more recently introduced NOACs. With the increasing use of NOACs and the risks pertaining to anticoagulation therapy, it is essential to invest in education for pharmacists to address their knowledge gaps enabling them to confidently support patients receiving oral anticoagulants

Impact of frailty on the effectiveness and safety of non-vitamin K antagonist oral anticoagulants (NOACs) in patients with atrial fibrillation : a nationwide cohort study

Data on non-vitamin K antagonist oral anticoagulants (NOACs) use in patients with atrial fibrillation (AF) and frailty are scarce. Therefore, the impact of frailty on AF-related outcomes and benefit-risk profiles of NOACs in patients with frailty were investigated. Methods and results: AF patients initiating anticoagulation between 2013–2019 were included using Belgian nationwide data. Frailty was assessed with the Claims-based Frailty Indicator. Among 254 478 anticoagulated AF patients, 71 638 (28.2%) had frailty. Frailty was associated with higher all-cause mortality risks (adjusted hazard ratio (aHR) 1.48, 95% confidence interval (CI) (1.43–1.54)), but not with thromboembolism or bleeding. Among subjects with frailty (78 080 person-years of follow-up), NOACs were associated with lower risks of stroke or systemic embolism (stroke/SE) (aHR 0.77, 95%CI (0.70–0.86)), all-cause mortality (aHR 0.88, 95%CI (0.84–0.92)) and intracranial bleeding (aHR 0.78, 95%CI (0.66–0.91)), a similar major bleeding risk (aHR 1.01, 95%CI (0.93–1.09)) and higher gastrointestinal bleeding risk (aHR 1.19, 95%CI (1.06–1.33) compared to VKAs. Major bleeding risks were lower with apixaban (aHR 0.84, 95%CI (0.76–0.93)), similar with edoxaban (aHR 0.91, 95%CI (0.73–1.14)), and higher with dabigatran (aHR 1.16, 95%CI (1.03–1.30)) and rivaroxaban (aHR 1.11, 95%CI (1.02–1.21)) compared to VKAs. Apixaban was associated with lower major bleeding risks compared to dabigatran (aHR 0.72, 95%CI (0.65–0.80)), rivaroxaban (aHR 0.78, 95%CI (0.72–0.84)) and edoxaban (aHR 0.74, 95%CI (0.65–0.84)), but mortality risk was higher compared to dabigatran and edoxaban. Conclusion: Frailty was an independent risk factor of death. NOACs had better benefit-risk profiles than VKAs in patients with frailty, especially apixaban, followed by edoxaban