Optimizing anticoagulation therapy for in-hospital patients on direct oral anticoagulants: a single-centre modified Delphi study.

AIMS: The management of patients treated with direct oral anticoagulants (DOACs) during hospitalization is a common challenge in clinical practice. Although bridging is generally not recommended, too often DOACs are switched to parenteral therapy with low molecular weight heparins. Our objectives were to update a local guideline for perioperative DOAC management and to develop a guideline for the anticoagulation management in non-surgical patients regarding temporary DOAC discontinuation. METHODS: We executed a two-step modified Delphi study in a 1000-bed university hospital in Belgium. The Delphi questionnaires were developed based on a literature review and a telephone survey of prescribers. Two expert panels were established: one dedicated to perioperative DOAC management and the other to DOAC management in non-surgical patients. Both panels completed two rounds, commencing with an individual and online round, followed by a face-to-face group session. RESULTS: After the two-round Delphi process, the updated perioperative guideline on DOAC management included reasons for delaying the resumption of DOACs following surgery, such as oral intake not possible, the probability of re-intervention within 3 days, and insufficient haemostasis (e.g. active clinically significant haematoma, haemorrhagic drains or wounds). Furthermore, a guideline for non-surgical hospitalized patients was developed, outlining possible reasons for interrupting DOAC therapy. Both guidelines offer clear anticoagulation therapy strategies corresponding to the identified scenarios. CONCLUSIONS: We have updated and developed guidelines for DOAC management in surgical and non-surgical patients during hospitalization, which aim to support prescribers and to enhance targeted prescription review by hospital pharmacists.

Trends in oral anticoagulant use in patients with atrial fibrillation in Belgium from 2013 to 2019: A nationwide cohort study.

AIM: 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, sex and physician's specialty may be present. Therefore, incident and prevalent use of OACs, NOACs and VKAs, stratified by age, sex and prescriber, and factors associated with the choice of OAC were investigated. METHODS: Using two Belgian nationwide healthcare databases, AF patients ≥45 years old with ≥1 OAC prescription claim between 2013 and 2019 were identified. OAC use was investigated per half-year. Factors influencing NOAC vs. VKA initiation were identified by multivariable logistic regression. RESULTS: Among 448 661 included OAC-treated AF patients, 297 818 were newly treated. Incident OAC use ranged from 45-49 to 42-44 users/10 000 persons between 2013 and 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 (25.3% vs. 33.0% between 2013 and 2019) and female subjects had 5% significantly lower odds of NOAC vs. VKA initiation than men. CONCLUSION: Since 2013, prevalent anticoagulant use increased almost one third in Belgium, while incident use was stable. Potential (N)OAC underuse in women requires further exploration.

Minimal Adherence Threshold to Non-Vitamin K Antagonist Oral Anticoagulants in Patients with Atrial Fibrillation to Reduce the Risk of Thromboembolism and Death: A Nationwide Cohort Study.

PURPOSE: Poor adherence to non-vitamin K antagonist oral anticoagulants (NOACs) may raise thromboembolic risks in patients with atrial fibrillation (AF). However, the minimal adherence to maintain the protective effect of NOACs is currently unknown. Therefore, we investigated thresholds of NOAC adherence in association with thromboembolic and mortality risks. METHODS: Patients with AF initiating NOACs between 2013 and 2019 were identified in Belgian nationwide data. Adherence was measured using the proportion of days covered (PDC) after one year of treatment. Inverse probability of treatment weighted Cox regression was used to investigate outcomes. RESULTS: 92,111 persons were included (250,750 person-years). Compared to NOAC users with a one-year PDC of 100%, significantly higher risks of stroke or systemic embolism were observed among NOAC users with PDCs of 85-89% (adjusted hazard ratio (aHR) 1.35, 95% confidence interval (CI) (1.19-1.54)), 80-84% (aHR 1.31, 95%CI (1.08-1.58)) and < 80% (aHR 1.64, 95%CI (1.34-2.01)), while no significant differences were observed among NOAC users with one-year PDCs of 95-99% (aHR 1.02, 95%CI (0.94-1.12)) or 90-94% (aHR 1.06, 95%CI (0.95-1.18)). Significantly higher risks of all-cause mortality were observed with decreasing levels of NOAC adherence, which were already higher among NOAC users with a one-year PDC of 90-94% versus 100% (aHR 1.09, 95%CI (1.01-1.17)). Findings were similar with once-daily and twice-daily dosed NOACs. CONCLUSION: Poor adherence to NOACs is associated with increased risks of thromboembolism and all-cause mortality. The minimal adherence threshold should be ≥ 90%, preferably even ≥ 95%.

Pharmacodynamic Drug-Drug Interactions and Bleeding Outcomes in Patients with Atrial Fibrillation Using Non-Vitamin K Antagonist Oral Anticoagulants: a Nationwide Cohort Study.

PURPOSE: Pharmacodynamic drug-drug interactions (PD DDIs) may influence the safety of non-vitamin K antagonist oral anticoagulants (NOACs), but the extent to which PD DDIs increase bleeding risks, remains unclear. Therefore, the impact of PD DDIs on bleeding outcomes in NOAC-treated patients with atrial fibrillation (AF) was investigated. METHODS: Using Belgian nationwide data, NOAC-treated AF patients were included between 2013-2019. Concomitant use of PD interacting drugs when initiating NOAC treatment was identified. RESULTS: Among 193,072 patients, PD DDIs were identified in 114,122 (59.1%) subjects. After multivariable adjustment, concomitant use of PD interacting drugs was associated with significantly higher risks of major or clinically-relevant non-major bleeding (adjusted hazard ratio (aHR) 1.19, 95% confidence interval (CI) (1.13-1.24)), gastrointestinal (aHR 1.12, 95%CI (1.03-1.22)), urogenital (aHR 1.21, 95%CI (1.09-1.35)) and other bleeding (aHR 1.28, 95%CI (1.20-1.36)), compared to NOAC-treated AF patients without PD interacting drug use. Increased bleeding risks were most pronounced with P2Y12 inhibitors (aHR 1.62, 95%CI (1.48-1.77)) and corticosteroids (aHR 1.53, 95%CI (1.42-1.66)), followed by selective serotonin or serotonin and norepinephrine reuptake inhibitors (SSRI/SNRI, aHR 1.26, 95%CI (1.17-1.35)), low-dose aspirin (aHR 1.14, 95%CI (1.08-1.20)) and non-steroidal anti-inflammatory drugs (NSAID, aHR 1.10, 95%CI (1.01-1.21)). Significantly higher intracranial bleeding risks in NOAC users were observed with SSRI/SNRIs (aHR 1.50, 95%CI (1.25-1.81)) and corticosteroids (aHR 1.49, 95%CI (1.21-1.84)). CONCLUSION: Concomitant use of PD interacting drugs, especially P2Y12 inhibitors and corticosteroids, was associated with higher major, gastrointestinal, urogenital, and other bleeding risks in NOAC-treated AF patients. Remarkably, higher intracranial bleeding risks were observed with SSRI/SNRIs and corticosteroids.

Impact of P-glycoprotein and/or CYP3A4-interacting drugs on effectiveness and safety of non-vitamin K antagonist oral anticoagulants in patients with atrial fibrillation: A meta-analysis.

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.

Physicians' and pharmacists' views and experiences regarding use of direct oral anticoagulants in clinical practice.

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.

Detection and management of clinically relevant drug-drug interactions with direct oral anticoagulants: an intervention study in community pharmacies.

INTRODUCTION: Direct oral anticoagulants (DOACs) are increasingly used and can be involved in clinically relevant drug-drug interactions (DDIs) that increase the risk of major bleeding or thromboembolism. Skilled drug interaction management is essential to ensure safe and effective use of DOACs. In this study, we aimed to investigate the impact of the detection and management of DDIs with DOACs in a real-life community pharmacy setting on the pharmacotherapy of DOAC users. METHODS: We conducted an intervention study in 201 community pharmacies in Belgium. On random days, patients purchasing DOACs or drugs known to interact with them were screened. When a DDI with the DOAC was detected, the pharmacist contacted the prescribing physician to discuss the management of the interaction. A previously developed practice-oriented DDI list accompanied by management plans for ambulatory care was used for both screening and management of the DDIs. RESULTS: In total, 751 patients were included, among whom 875 DDIs were identified, primarily pharmacodynamic DDIs (95.7 %). Predominant interacting drug classes included selective serotonin or serotonin and norepinephrine reuptake inhibitors (32.9 %), antiplatelets (30.9 %), and non-steroidal anti-inflammatory drugs (28.9 %). In 43.0 % of DDIs, an intervention was decided upon. At three-month follow-up, proposed pharmacotherapy changes had been implemented in 79.1 % of these DDIs. CONCLUSIONS: This study demonstrates that active screening and management of DDIs with DOACs in community pharmacies, in close collaboration with prescribing physicians, resulted in changes in pharmacotherapy in a substantial number of patients. This may contribute significantly to the safer utilisation of DOACs in high-risk populations.

Drug-drug interactions with direct oral anticoagulants: development of a consensus list for ambulatory care.

BACKGROUND: 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. AIM: 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. METHOD: 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. RESULTS: 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. CONCLUSION: We developed a consensus list with specific and straightforward management plans on potentially clinically relevant DDIs with DOACs, for use in ambulatory care.

Therapeutic dilemmas with benzodiazepines and Z-drugs: insomnia and anxiety disorders versus increased fall risk: a clinical review.

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.

Impact of P-glycoprotein and CYP3A4-interacting drugs on clinical outcomes in patients with atrial fibrillation using non-vitamin K antagonist oral anticoagulants: a nationwide cohort study.

AIMS: The clinical relevance of common pharmacokinetic interactions with non-vitamin K antagonist oral anticoagulants (NOACs) often remains unclear. Therefore, the impact of P-glycoprotein (P-gp) and CYP3A4 inhibitors and inducers on clinical outcomes in NOAC-treated patients with atrial fibrillation (AF) was investigated. METHODS AND RESULTS: AF patients were included between 2013 and 2019 using Belgian nationwide data. Concomitant use of P-gp/CYP3A4-interacting drugs at the time of NOAC initiation was identified. Among 193 072 NOAC-treated AF patients, 46 194 (23.9%) and 2903 (1.5%) subjects concomitantly used a P-gp/CYP3A4 inhibitor or inducer, respectively. After multivariable adjustment, concomitant use of P-gp/CYP3A4 inhibitors was associated with significantly higher major bleeding [adjusted hazard ratio (aHR) 1.24, 95% confidence interval (CI) (1.18-1.30)] and all-cause mortality risks [aHR 1.07, 95% CI (1.02-1.11)], but not with thromboembolism in NOAC-treated AF patients. A significantly increased risk of major bleeding was observed with amiodarone [aHR 1.27, 95% CI (1.21-1.34)], diltiazem [aHR 1.28, 95% CI (1.13-1.46)], verapamil [aHR 1.36, 95% CI (1.03-1.80)], ticagrelor [aHR 1.50, 95% CI (1.20-1.87)], and clarithromycin [aHR 1.55, 95% CI (1.14-2.11)]; and in edoxaban [aHR 1.24, 95% CI (1.06-1.45)], rivaroxaban [aHR 1.25, 95% CI (1.16-1.34)], and apixaban users [aHR 1.27, 95% CI (1.16-1.39)], but not in dabigatran users [aHR 1.07, 95% CI (0.94-1.23)]. Concomitant use of P-gp/CYP3A4 inducers (e.g. antiepileptic drugs like levetiracetam) was associated with a significantly higher stroke risk [aHR 1.31, 95% CI (1.03-1.68)], but not with bleeding or all-cause mortality. CONCLUSION: Concomitant use of P-gp/CYP3A4 inhibitors was associated with higher bleeding and all-cause mortality risks in NOAC users, whereas the use of P-gp/CYP3A4 inducers was associated with higher stroke risks.

Adherence and persistence to oral anticoagulants in patients with atrial fibrillation: A Belgian nationwide cohort study.

Background: Since non-vitamin K antagonist oral anticoagulants (NOACs) do not require coagulation monitoring, concerns of lower adherence and persistence to NOACs than vitamin K antagonists (VKAs) have been raised. Moreover, little is known on the frequency of permanent cessation and switching between anticoagulants in patients with atrial fibrillation (AF). Therefore, persistence, reinitiation, switching and adherence to oral anticoagulants (OACs) were investigated. Materials and methods: AF patients with a first OAC prescription claim between 2013 and 2019 were identified in Belgian nationwide data. Persistence, reinitiation and switching were estimated using Kaplan-Meier analyses. Adherence was investigated using the proportion of days covered (PDC). Predictors for non-adherence and non-persistence were identified by multivariable logistic regression. Results: Among 277,782 AF patients, 69.6% NOAC and 37.2% VKA users were persistent after 1 year, whereas 44.3% and 18.9% after 5 years, respectively. After one year, 67.1% rivaroxaban, 68.1% dabigatran, 69.8% apixaban, and 76.9% edoxaban users were persistent. Among subjects having discontinued NOAC or VKA treatment, 75.4% and 46.1% reinitiated any OAC within 5 years, respectively. VKAs were more frequently switched to NOACs than vice versa (17.6% versus 2.5% after 1 year). After 1 year, a high PDC (≥ 90%) was observed in 87.8% apixaban, 88.6% dabigatran, 91.3% rivaroxaban, and 94.7% edoxaban users (90.2% NOAC users). Adherence and persistence were higher in older, female subjects, while lower in subjects with dementia or hyperpolypharmacy. Conclusion: Adherence and persistence to NOACs were high. However, 10% of subjects were non-adherent after 1 year and one-fourth did not reinitiate anticoagulation within 5 years after NOAC discontinuation.

Prevalence of potentially inappropriate prescribing in older adults in Central and Eastern Europe: a systematic review and synthesis without meta-analysis.

We aimed to systematically review the prevalence of potentially inappropriate prescribing (PIP) in older adults in Central and Eastern Europe (CEE) in all care settings. We searched Embase and MEDLINE (up to June 2019) and checked the reference lists of the included studies and relevant reviews. Eligible studies used validated explicit or implicit tools to assess the PIP prevalence in older adults in CEE. All study designs were considered, except case‒control studies and case series. We assessed the risk of bias using the Joanna Briggs Institute Prevalence Critical Appraisal Tool and the certainty of evidence using the GRADE approach. Meta-analysis was inappropriate due to heterogeneity in the outcome measurements. Therefore, we used the synthesis without meta-analysis approach-summarizing effect estimates method. This review included twenty-seven studies with 139,693 participants. Most studies were cross-sectional and conducted in high-income countries. The data synthesis across 26 studies revealed the PIP prevalence: the median was 34.6%, the interquartile range was 25.9-63.2%, and the range was 6.5-95.8%. The certainty of this evidence was very low due to the risk of bias, imprecision, and inconsistency. These findings show that PIP is a prevalent issue in the CEE region. Further well-designed studies conducted across countries are needed to strengthen the existing evidence and increase the generalizability of findings.

Guidance for appropriate use of psychotropic drugs in older people.

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.

The impact of underweight and obesity on outcomes in anticoagulated patients with atrial fibrillation: A systematic review and meta-analysis on the obesity paradox.

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, ≥30 and ≥40 kg/m2 , respectively) compared to normal BMI anticoagulated AF patients (BMI 18.5 to <25 kg/m2 ). In contrast, thromboembolic (RR 1.92, 95%CI [1.28-2.90]) and mortality (RR 3.57, 95%CI [2.50-5.11]) risks were significantly increased in underweight anticoagulated AF patients (BMI <18.5 kg/m2 ). In overweight and obese anticoagulated AF patients, the risks of major bleeding (RR 0.86, 95%CI [0.76-0.99]; and RR 0.88, 95%CI [0.79-0.98], respectively) and intracranial bleeding (RR 0.75, 95%CI [0.58-0.97]; and RR 0.57, 95%CI [0.40-0.80], respectively) were also significantly lower compared to normal BMI patients, while similar risks were observed in underweight and morbidly obese patients. This meta-analysis demonstrated lower thromboembolic and mortality risks with increasing BMI. However, as this paradox was driven by results from randomized studies, while observational studies rendered more conflicting results, these seemingly protective effects should still be interpreted with caution.

Ghent Older People's Prescriptions Community Pharmacy Screening (GheOP3S)-Tool Version 2: Update of a Tool to Detect Drug-Related Problems in Older People in Primary Care.

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.

Appropriateness of direct oral anticoagulant dosing in patients with atrial fibrillation according to the drug labelling and the EHRA Practical Guide.

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.

Medication Counselling in Older Patients Prior to Hospital Discharge: A Systematic Review.

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.

Community pharmacy-based study of adherence to non-vitamin K antagonist oral anticoagulants.

OBJECTIVE: This 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. METHODS: A 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). RESULTS: A 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 <25), with unintentional non-adherence (forgetfulness) most frequently reported (15.4%). Although two-thirds of NOAC users indicated to experience adverse drug reactions, the BMQ demonstrated a positive attitude towards NOAC therapy, where necessity beliefs outweigh the concerns. CONCLUSIONS: Our 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.