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Background Non-vitamin K antagonist oral anticoagulants (NOACs) are increasingly preferred over vitamin K antagonists (VKAs) in atrial fibrillation (AF) management. However, differences in oral anticoagulant (OAC) prescribing according to patient's age, patient's sex and physician's specialty may be present. Purpose To investigate the incident and prevalent use of OACs, NOACs and VKAs, stratified by age, sex and prescriber, and factors associated with the choice of OAC on a full-population scale. Methods Using two Belgian nationwide healthcare databases, AF patients ≥45 years old with ≥1 OAC prescription claim between January 1st, 2013 and December 31st, 2019 were identified. OAC use was investigated per half-year with a repeated cross-sectional design, based on medication prescription claims on a day-to-day basis. Incident use was defined as the first OAC use during the study period in OAC-naïve AF patients, whereas prevalent OAC use was defined as at least 1 OAC dispensing during a specific half-year. Factors influencing NOAC versus VKA initiation were identified by multivariable logistic regression models. Results Among 448,661 included OAC-treated AF patients (260,184 prevalent NOAC and 188,477 prevalent VKA users), 297,818 were newly-treated (232,739 incident NOAC and 65,079 incident VKA users). The mean age of incident NOAC and VKA users was 76±10 and 71±12 years, and 48% and 47% were female, respectively. Incident OAC use ranged from 45–49 to 42–44 users/10,000 persons between 2013–2019, whereas prevalent OAC use increased from 337 to 435 users/10,000 persons. Incident and prevalent NOAC use exceeded VKA use since 2013 and 2015 respectively, and NOACs represented 92% of incident and 81% of prevalent OAC users in 2019. Apixaban was the most frequently used NOAC since 2016. NOACs were significantly more prescribed by cardiologists and to older patients, whereas VKAs were more initiated in patients with cardiovascular, renal and hepatic comorbidities. Prevalent OAC use increased less in women than men (+25% versus +33% between 2013–2019) and female subjects had a 5% significantly lower odds of NOAC versus VKA initiation than men after multivariable adjustment. Conclusions Prevalent anticoagulant use increased with 29% in Belgium between 2013 and 2019. However, potential (N)OAC underuse among female AF patients was observed. Funding Acknowledgement Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Research Foundation Flanders (FWO)

AIMS: P-glycoprotein (P-gp) and CYP3A4-interacting drugs influence plasma levels of non-vitamin K antagonist oral anticoagulants (NOACs). However, the clinical relevance is questioned. Therefore, the impact of pharmacokinetically-interacting drugs on the effectiveness and safety of NOACs in patients with atrial fibrillation (AF) was investigated. METHODS: A meta-analysis was performed based on randomized controlled trials and observational studies retrieved from Pubmed and Embase that investigated the impact of concomitantly used P-gp/CYP3A4-interacting drugs on the risk-benefit profile of NOACs in AF patients. RESULTS: Fifteen studies were included, investigating 21 711 and 306 421 NOAC-treated AF patients with and without P-gp/CYP3A4 inhibitor use respectively, while only 1 study included P-gp/CYP3A4 inducers. In NOAC-treated AF patients, concomitant use of P-gp/CYP3A4 inhibitors was associated with significantly higher major bleeding (relative risk [RR] 1.10, 95% confidence interval [CI; 1.01-1.19]) and all-cause mortality risks (RR 1.14, 95%CI [1.05-1.23]) compared to not using P-gp/CYP3A4 inhibitors, while the risks of stroke/systemic embolism (RR 0.88, 95%CI [0.77-1.01]), intracranial bleeding (RR 0.89, 95%CI [0.68-1.15]) and gastrointestinal bleeding (RR 1.09, 95%CI [0.91-1.30]) were not significantly different. Concomitant use of amiodarone with NOACs was associated with lower thromboembolic (RR 0.75, 95%CI [0.61-0.92]), similar major bleeding (RR 0.92, 95%CI [0.80-1.07]) but higher mortality risks (RR 1.21, 95%CI [1.05-1.39]). Coadministration of verapamil or diltiazem was associated with higher major bleeding risks (RR 1.64, 95%CI [1.31-2.06]), but comparable thromboembolic (RR 1.10, 95%CI [0.75-1.61]) and mortality risks (RR 1.01, 95%CI [0.77-1.33]). CONCLUSION: Given the higher bleeding and mortality risks in NOAC-treated AF patients concomitantly using P-gp/CYP3A4 inhibitors, close monitoring is warranted.

Purpose The aim of this clinical review was to summarise the existing knowledge on fall risk associated with benzodiazepines (BZDs) and Z-drugs in older people with focus on appropriate prescribing, including deprescribing. Methods We conducted a literature search in June 2021 in PubMed and Embase with citation and reference checking. Personal reference libraries and international websites were also used. Keywords for the searches included “benzodiazepines”, “Z-drugs”, “falls”, “deprescribing”, “fall-risk-increasing-drugs”, “inappropriate prescribing”, “older people” and matching synonyms. We discuss use of BZDs and Z-drugs, potential fall-related adverse reactions, alternatives for and deprescribing of BZDs and Z-drugs in older persons. Results BZDs and Z-drugs differ in fall-related adverse effect profile. They contribute to fall risk through orthostatic hypotension, dizziness and/or imbalance, sedation, muscular weakness, ataxia, etc. Fall incidents contribute significantly to mortality and morbidity. Therefore, there is a need for appropriate prescribing and use of BZDs and Z-drugs in older people. In practice, this means pertaining to a strict indication, strongly consider to non-pharmacological alternatives, limit use to the lowest dose and the shortest duration possible. Judicious deprescribing should be considered and encouraged as well. Practical resources, tools and algorithms are available to guide and assist clinicians in deprescribing BZDs and Z-drugs. Conclusions Prescribing BZDs and Z-drugs should be done in a well-considered way in fall-prone older people. A good overview and insight in the fall-related adverse effects of these drugs, as well as the availability of different strategies to increase the appropriate use, including deprescribing initiatives, can assist clinicians in clinical decision-making.

Background The Ghent Older People’s Prescriptions community Pharmacy Screening (GheOP3S)-tool was developed in 2016 as a screening tool to detect drug-related problems (DRPs) and to help in performing medication reviews in older people (≥ 65 years). Objective This study aimed to revise and update the GheOP3S-tool. Methods Users’ comments were collected to improve the usability and appropriateness of the original GheOP3S-tool, followed by a two-round modified Delphi process according to the RAND/UCLA appropriateness method. This included a literature review, a round zero meeting, a first written round (with 15 international and multidisciplinary experts) and a second face-to-face round (with 11 experts) to change, delete or add GheOP3S-criteria. An additional third round with 14 community pharmacists was organised to preserve criteria applicable in the current community pharmacy practice. Results The updated GheOP3S-tool consists of five lists of DRPs and a new addendum containing medications that should be avoided or used with caution in older people with reduced renal function. During the first two rounds, related criteria were grouped, 14 criteria were added and 17 criteria were deleted from the original tool. All criteria were deemed applicable in round 3. This led to a final tool (version 2) with 64 GheOP3S-criteria. Conclusion GheOP3S-criteria were revised and updated according to experts’ agreement on their clinical relevance and recent scientific evidence. Future studies should investigate the impact of pharmacist-led medication reviews with GheOP3S-tool version 2 on clinical, humanistic and economic outcomes in primary care. Supplementary Information The online version contains supplementary material available at 10.1007/s40266-021-00862-6.

Although obesity is associated with the development and progression of atrial fibrillation (AF), an obesity paradox may be present, illustrated by seemingly protective effects of obesity on AF-related outcomes. Body mass index (BMI) has an impact on outcomes in AF patients using oral anticoagulants. After searching Medline and Embase, meta-analysis of results of four randomized and five observational studies demonstrated significantly lower risks of stroke or systemic embolism (RR 0.80, 95%CI [0.73-0.87]; RR 0.63, 95%CI [0.57-0.70]; and RR 0.42, 95%CI [0.31-0.57], respectively) and all-cause mortality (RR 0.73, 95%CI [0.64-0.83]; RR 0.61, 95%CI [0.52-0.71]; and RR 0.56, 95%CI [0.47-0.66], respectively) in overweight, obese and morbidly obese anticoagulated AF patients (BMI 25 to = 30 and >= 40 kg/m(2), respectively) compared to normal BMI anticoagulated AF patients (BMI 18.5 to

Background This study aimed to evaluate the prevalence of potential drug-drug interactions (DDIs) and the appropriateness of direct oral anticoagulant (DOAC) dosing according to both the Summary of Product Characteristics (SmPC) and the European Heart Rhythm Association (EHRA) Practical Guide in a ‘real-world’ sample of non-valvular atrial fibrillation (NVAF) patients. Methods and results Data of a cross-sectional observational study in a primary care sample of 654 long-term DOAC users were used for this sub-analysis. A total of 262 potential DDIs were identified in 220 patients (33.6%). Pharmacodynamic DDIs were present in 163 patients (24.9%) and pharmacokinetic DDIs in 82 patients (12.5%). One-third of patients (33.8%) received reduced DOAC dose. According to the dosing recommendations in the SmPC, 81.7% of DOACs were dosed appropriately. According to the EHRA recommendations, 76.6% of DOACs were dosed appropriately. Dosing recommendations were consistent for 90.7% of patients, with both the SmPC and EHRA Practical Guide considering DOACs dosed appropriately in 74.5% of patients, overdosed in 7.8%, underdosed in 7.6% and contraindicated in 0.8%. However, for the remaining 9.3% dosing recommendations differed between SmPC and EHRA. Conclusions This ‘real-world’ analysis of DOAC dosing demonstrated that in about one-third of NVAF patients potential DDIs were present. In 18.3% and 23.4% of patients, DOACs were dosed inappropriately according to the SmPC and EHRA Practical Guide respectively. In almost 10% of the study population dosing advice was inconsistent between both references. More research is needed to ensure appropriate DOAC dosing in this ‘grey zone’ population.

Direct oral anticoagulants (DOACs) can be involved in clinical relevant drug-drug interactions (DDIs) which may compromise safe and effective use. However, assessing the clinical relevance of DDIs with DOACs and managing these interactions optimally, can be challenging in clinical practice.To develop a practice-oriented list of potentially clinically relevant DDIs with DOACs with corresponding management plans for which it is important to screen in ambulatory care.The RAND/UCLA appropriateness method was used to develop the DOACs DDI list. In a first step a preliminary list was compiled of potentially clinically relevant DDIs per DOAC (apixaban, dabigatran, edoxaban, rivaroxaban) using five reference sources. Subsequently, a two-step modified Delphi process involving a multidisciplinary panel (n = 10) including both pharmacists and physicians with expertise in all decision-making disciplines involved in care for patients using DOACs and with diversity of practice setting, was used to reach expert agreement on a final list of DDIs with corresponding management plans.After a two-step consensus round, 71 DDIs for 20 different interacting drugs were included: five pharmacodynamic, nine pharmacokinetic inhibitor and six pharmacokinetic inducer interacting drugs. Considerations raised and discussed by the panellists were related to (1) the necessity of the interacting drug, (2) the manageability of the DDI (whether there are any alternatives), (3) the (clinical) evidence-base for the DDI and (4) the (potential) consequences of the DDI.We developed a consensus list with specific and straightforward management plans on potentially clinically relevant DDIs with DOACs, for use in ambulatory care.

Psychotropic drugs are widely prescribed in older people although their use is associated with important risks. In this position paper, we discuss the appropriateness of using these medications in older people in terms of different aspects such as indications, contraindications, dosing, adverse drug reactions, interactions and duration of therapy. Consequently, we discuss different strategies to increase the appropriateness of therapy while formulating some practical recommendations to keep in mind when (de)prescribing psychotropic drugs in older people.

BACKGROUND: Older patients are regularly exposed to multiple medication changes during a hospital stay and are more likely to experience problems understanding these changes. Medication counselling is often proposed as an important component of seamless care to ensure appropriate medication use after hospital discharge. OBJECTIVES: The purpose of this systematic review was to describe the components of medication counselling in older patients (aged ≥ 65 years) prior to hospital discharge and to review the effectiveness of such counselling on reported clinical outcomes. METHODS: Using Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) methodology (PROSPERO CRD42019116036), a systematic search of MEDLINE, EMBASE and CINAHL was conducted. The QualSyst Assessment Tool was used to assess bias. The impact of medication counselling on different outcomes was described and stratified by intervention content. RESULTS: Twenty-nine studies were included. Fifteen different components of medication counselling were identified. Discussing the dose and dosage of patients' medications (19/29; 65.5%), providing a paper-based medication list (19/29; 65.5%) and explaining the indications of the prescribed medications (17/29; 58.6%) were the most frequently encountered components during the counselling session. Twelve different clinical outcomes were investigated in the 29 studies. A positive effect of medication counselling on medication adherence and medication knowledge was found more frequently, compared to its impact on hard outcomes such as hospital readmissions and mortality. Yet, evidence remains inconclusive regarding clinical benefit, owing to study design heterogeneity and different intervention components. Statistically significant results were more frequently observed when counselling was provided as part of a comprehensive intervention before discharge. CONCLUSIONS: Substantial heterogeneity between the included studies was found for the components of medication counselling and the reported outcomes. Study findings suggest that medication counselling should be part of multifaceted interventions, but the evidence concerning clinical outcomes remains inconclusive.

AIM Direct oral anticoagulants (DOACs) are increasingly used compared to vitamin K antagonists (VKAs). Guidelines advocate a structured multidisciplinary approach in the management of patients treated with DOACs. The aim of this study was to assess the views and experiences of physicians and pharmacists regarding DOAC use in clinical practice. METHODS An online questionnaire was sent to both primary (general practitioners [GPs], community pharmacists) and secondary healthcare professionals (cardiologists, residents in internal medicine and hospital pharmacists) between March and July 2020. The questionnaire covered four topics: (i) current practice, (ii) prescribing behaviour (only for physicians), (iii) self-perceived knowledge about DOACs and (iv) views and opinions about DOACs versus VKAs. RESULTS In total, 110 physicians and 111 pharmacists completed the survey. Healthcare professionals in secondary care had more experience with DOACs and felt more confident with higher self-perceived knowledge about DOACs compared to their colleagues in primary care. Healthcare professionals' self-perceived knowledge was more or less complementary, for example physicians felt less confident in managing drug-drug interactions (DDIs) where pharmacists reported being more confident in this topic. Physicians reported uncertainties on the potential impact of risk factors - such as older age, lower body weight and DDIs - on appropriate DOAC dosing. CONCLUSION Complementarity in physicians' and pharmacists' self-perceived knowledge levels of DOACs may facilitate and necessitate future multidisciplinary collaboration initiatives for the management and follow-up of DOAC patients.

Atrial fibrillation and non-vitamin K antagonist oral anticoagulants: from clinical trials to real-world clinical practice. For decades, vitamin K antagonists (VKAs) were the only oral anticoagulants available for the prevention of thromboembolism in patients with atrial fibrillation (AF). Since 2012, non-vitamin K antagonist oral anticoagulants (NOACs) are available for this indication, which have proven to be at least as effective and safe as VKAs in randomized controlled trials (RCTs). NOACs have additional benefits, such as a fast onset of action, a fixed-dose regimen without requiring regular monitoring, less interactions and less intracranial bleeding. Their emergence has caused a paradigm shift in anticoagulation therapy, with NOACs being the anticoagulant of choice compared to VKAs. Since strict in- and exclusion criteria were used in the pivotal RCTs, concerns have risen regarding the generalizability of these results to real-life clinical practice in patients with multiple comorbidities. In this manuscript, this extrapolation is discussed, focusing on 4 different topics regarding appropriate NOAC use: the management of AF patients with a single stroke risk factor, the importance of an optimal therapy adherence, potential drug-drug interactions with NOACs and addressing a geriatric AF patient after a fall. Hopefully, this manuscript will help guide clinicians in the optimal use of NOACs in their daily clinical practice.

Psychotropic drugs are widely prescribed in older people although their use is associated with important risks. In this position paper, we discuss the appropriateness of using these medications in older people in terms of different aspects such as indications, contraindications, dosing, adverse drug reactions, interactions and duration of therapy. Consequently, we discuss different strategies to increase the appropriateness of therapy while formulating some practical recommendations to keep in mind when (de)prescribing psychotropic drugs in older people.

ObjectiveThis study aimed to assess implementation adherence (how well the patient’s actual intake matches the prescribed dosing regimen) to non-vitamin K antagonist oral anticoagulants (NOACs) and to explore experiences with and beliefs about NOACs in a real-world sample of long-term NOAC users.MethodsA cross-sectional observational study was conducted in home-dwelling adults who started taking a NOAC at least 1 year prior to inclusion. Pharmacy dispensing data were used to calculate the Medication Possession Ratio (MPR). Patients were recruited in 158 community pharmacies in Flanders, Belgium. They completed a questionnaire collecting basic characteristics and exploring self-reported adherence to NOACs (using the Medication Adherence Report Scale, MARS) and experiences with and beliefs about NOACs (using the Beliefs about Medicines Questionnaire, BMQ).ResultsA total of 766 patients (mean age 76.2±8.8 years, median CHA2DS2-VASc score 4 (IQR=3–4)) were included. The majority (93.5%) used NOAC for stroke prevention in atrial fibrillation. The median MPR was 95.2% (IQR=87.8–99.7) which corresponds with half of the study population not taking their NOAC on at least 17 cumulative days per year. Almost 21% of participants reported non-adherence on the MARS (score ConclusionsOur data indicate that long-term NOAC users have high implementation adherence and a positive attitude towards NOAC therapy. However, taking into account patients’ thromboembolic risk and NOACs’ short half-lives, further optimisation of NOAC use seems warranted in this population.

Background The emergence of non-vitamin K antagonist oral anticoagulants (NOAC) has caused a paradigm shift in anticoagulation therapy, with NOAC being increasingly used compared to vitamin K antagonists. Despite the numerous RCTs with NOAC, further follow-up on how this high risk new drug class is used in real-world clinical practice is warranted. Purpose This study aimed to describe NOAC use in a primary care sample of long-term NOAC users, and investigated (i) adherence, (ii) patients' perceptions, (iii) drug interactions and (iv) appropriateness of dosing. Methods A cross-sectional observational study was conducted in 158 community pharmacies. Participants were home-dwelling adults treated with a NOAC for at least one year. They completed a questionnaire collecting data on socio-demographics, clinical characteristics, current medication use, self-reported adherence to NOAC (via Medication Adherence Report Scale, MARS), and beliefs and perceptions about NOAC (via Beliefs about Medicines Questionnaire, BMQ). Adherence to NOAC (self-reported (MARS) and calculated using pharmacy dispensing data (Medication Possession Ratio (MPR)); patients' beliefs and perceptions about NOAC (BMQ); and prevalence of drug interactions and inappropriate dosing (using the recommendations in the summary of product characteristics (SmPC) and the 2018 European Heart Rhythm Association (EHRA) Practical Guide) were assessed. Results Participants (n=766) had a mean age of 76.2±8.8 years, several co-morbidities (median of 5 (IQR 4–6)) and high thromboembolic risk (median CHA2DS2-VASc score of 4 (IQR 3–4)). The majority (93.5%) used NOAC for non-valvular atrial fibrillation, while the other 6.5% used it for the prevention of recurrent deep vein thrombosis or pulmonary embolism. Forty point five percent of the study sample used rivaroxaban, 36.2% apixaban, 21.1% dabigatran and 2.2% edoxaban. About 85% was adherent according to MPR (MPR ≥80%) and self-reported adherence was also high (mean MARS score 24.6±1.0). Two-thirds reported at least one adverse event of the NOAC, with easy bruising/bleeding being most prevalent (40.2% of patients). BMQ showed that 91.3% of patients favoured the “necessity” over the “concerns” of NOAC use. Thirty-one percent of patients had ≥1 drug interaction(s) with NOAC; amiodarone (10.4% of patients), antiplatelet agents (9.7%) and NSAIDs (9.0%) were the most common interacting drugs. NOAC dosing was inappropriate in 15.9% of patients according to SmPC and in 23.1% according to EHRA. Intriguingly, underdosing was more common using the SmPC as reference, while overdosing was more common using the EHRA guideline. Conclusions This real-world analysis of NOAC use revealed high adherence and necessity beliefs, drug interactions in 30% of patients, and suboptimal dosing in about one fifth of patients. These findings can inform the design of targeted community pharmacist interventions to improve quality of NOAC use.

Poster presented at the conference.