Prevalence and trends in polypharmacy and excessive polypharmacy: a retrospective national database analysis (2012-2021).

BACKGROUND: Polypharmacy is a growing concern, impacting patient safety and healthcare costs. Monitoring its prevalence and temporal trends is essential for effective healthcare management. AIM: This study aimed to determine prevalence and trends of polypharmacy and excessive polypharmacy in Belgium. METHOD: Utilizing a federal claims database, medication data were analyzed from 2012 to 2021. Polypharmacy (≥ 5 medications) and excessive polypharmacy (≥ 10 medications) were evaluated, with prevalence calculated per 1000 inhabitants, and reported per year, age group and region. Linear regression estimated the impact of age and year on polypharmacy prevalence. RESULTS: In 2021, polypharmacy and excessive polypharmacy were reported in 135/1000 and 31/1000 Belgians respectively. Prevalence of both increased steadily from 2012 to 2021, with excessive polypharmacy rising more prominently. Among adults aged ≥ 65 years, prevalence rates were higher, with polypharmacy at 434/1000 and excessive polypharmacy at 106/1000. Regional variations were observed, with prevalence highest in the Walloons region. Patient age and year (2012-2021) were associated with both polypharmacy and excessive polypharmacy (p < 0.001). CONCLUSION: We observed increases in polypharmacy and excessive polypharmacy over a decade in Belgium, particularly among older adults. Efforts to monitor, manage, and optimize medication use are imperative to ensure safe and effective healthcare delivery.

Appropriateness of antithrombotics in geriatric inpatients with atrial fibrillation: a retrospective, cross-sectional study.

BACKGROUND: Atrial fibrillation occurs in nearly half of geriatric inpatients and is a major cause of morbidity and mortality. Suboptimal anticoagulation use is an important concern in this population. This study aimed to evaluate the appropriateness of antithrombotic therapies in this patient cohort. METHODS: A retrospective analysis was conducted on the geriatric wards of a teaching hospital in Belgium, on a background of clinical pharmacy services. The first 90 atrial fibrillation patients from 2020 to 2022 were included if they received an oral anticoagulant. We assessed utilisation and appropriateness of antithrombotics at discharge, examined reasons for guideline deviations, and explored factors associated with underdosing. Temporal associations for appropriateness and type of anticoagulant (vitamin K antagonist (VKA) vs direct oral anticoagulant (DOAC)) were assessed. RESULTS: The mean age of patients was 86.5 (±5.3) years and the median CHA2DS2-VASc score was 5 (interquartile range (IQR) 4-6). At discharge, 256 (94.8%) patients used a DOAC; nine (3.3%) used a VKA; one (0.4%) a DOAC-antiplatelet combination, and in four patients (1.5%) all antithrombotics were discontinued. The majority (64.4%) of patients received reduced DOAC doses with apixaban prescribed in 40.7%. In 39 (14.4%) patients, antithrombotic use was considered inappropriate, mostly without a rationale (23/39). Year 2022 (odds ratio (OR) 0.104; 95% confidence interval (CI), 0.012-0.878) was the sole determinant for underdosing. No significant differences were found with respect to appropriateness (p=0.533) or anticoagulant class (p=0.479) over time. CONCLUSION: Most geriatric inpatients received a justified reduced DOAC dose. A significant proportion was managed inappropriately with underdosing (= unjustified reduced dose) being most common. Frequently no rationale was provided for deviating from trial-tested doses.

Agreement Between a Colorimetric Assay and Ultra-Performance Liquid Chromatography-Tandem Mass Spectrometry for Quantifying Paracetamol Plasma Concentrations.

Special populations, like geriatric patients, experience altered paracetamol pharmacokinetics (PK), complicating pain management. More PK research is essential to optimize paracetamol (acetaminophen) dosing. Yet, the reference method ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) is not readily available. Therefore, we aimed to evaluate the agreement between UPLC-MS/MS and the more accessible colorimetric Roche acetaminophen (ACETA) assay in quantifying paracetamol plasma concentrations, to facilitate PK studies and therapeutic drug monitoring for pain management. Patient data and plasma samples were obtained from a prospective study including geriatric patients admitted to the geriatric wards. ACETA and UPLC-MS/MS assays were performed in two separate laboratories. Bland-Altman plot and Passing-Bablok regression were used to assess agreement. Accuracy was evaluated using the McNemar test for a threshold value of 10 mg/L. Population PK modeling was employed to bridge PK data obtained from both methods (NONMEM 7.5). A total of 242 plasma sample pairs were available from 40 geriatric patients (age range, 80-95 years). Paracetamol plasma concentrations from ACETA (median 9.8 [interquartile range 6.1-14.4] mg/L) and UPLC-MS/MS (9.5 [6.2-14.8] mg/L) did not differ significantly (P > 0.05). No significant proportional nor additive bias was observed between both assay methods. The classification accuracy (at threshold 10 mg/L) was 85% (P = 0.414). The conversion factor between ACETA and UPLC-MS/MS was estimated at 1.06 (relative standard error 5%), yet with a 13.4% (relative standard error 23%) interindividual variability. ACETA assay showed no systematic bias in comparison with the UPLC-MS/MS assay in determining paracetamol exposure in geriatric blood samples despite the imprecision.

Therapy and guideline adherence at a multidisciplinary hypertension clinic: A prospective, observational study.

BACKGROUND: Hypertension is highly prevalent and remains one of the most frequent and preventable causes of cardiovascular morbidity and mortality. Yet, suboptimal blood pressure control is common. Hypertension clinics might play an important role in improving target attainment, by targeting drug therapy adherence, improving guideline compliance and by involving pharmacists. OBJECTIVES: We aimed to characterize patient drug therapy adherence, prescriber guideline compliance and pharmacist interventions at the hypertension clinic. METHODS: A prospective observational study was performed at the hypertension clinic of a large, academic hospital. Adult Dutch-speaking patients were eligible for inclusion. Following data were collected: patient demographics, medication use, patient adherence to prescribed antihypertensive drug therapies according to the BAASIS tool and prescriber compliance to the 2018 European Society of Cardiology (ESC) hypertension guidelines. RESULTS: A cohort of 108 patients was included with 51.9% male and aged 65 (IQR: 52-75) years. In total, 104 patients took at least 1 antihypertensive drug and 46 patients (44.2%) were classified as non-adherent with regard to their antihypertensive treatment; 82 patients (78.8%) had suboptimal blood pressure control. Compliance with the ESC guidelines was 66.3% prior to the consultation at the clinic and significantly increased to 77.9% thereafter (p = 0.0015). The clinical pharmacist performed a medication review for 27 patients with a total of 44 recommendations and an acceptance rate of 59.1%. CONCLUSION: A visit to the multidisciplinary hypertension clinic improved prescriber guideline compliance and the use of single pill combinations. Involvement of a clinical pharmacist could be beneficial to further improve patient drug therapy adherence and guideline compliance.

Predictors for unplanned hospital admissions in community dwelling adults: A dynamic cohort study.

BACKGROUND: Polypharmacy and inappropriate medication use are associated with unplanned hospital admissions. Targeted interventions might reduce the hospitalization risk. Yet, it remains unclear which patient profiles derive the largest benefit from such interventions. OBJECTIVE: The aim of this study was to determine independent risk factors, among which polypharmacy, for unplanned hospital admissions in a cohort of community dwelling adults. METHODS: A retrospective study was performed using a large general practice registry and an insurance database in Flanders, Belgium. Community dwelling adults aged 40 years or older with data for 2013-2015 were included. The index date was the last general practitioner contact in 2014. Determinants were collected during the preceding year. Unplanned hospital admissions were determined during the year after the index date. Univariable logistic regression models were fitted on each risk factor for an unplanned hospital admission as the primary outcome. Two multivariable models were derived. RESULTS: In total, 40411 patients were included and 2126 (5.26%) experienced an unplanned hospital admission. Mean age was 58.3 (±12.3) years. The two models identified the following determinants for an unplanned hospital admission: excessive polypharmacy, older age, male sex, number of comorbidities, atrial fibrillation, chronic obstructive pulmonary disease or stroke, low hemoglobin, use of hypnotics, antipsychotics, antidepressants or antiepileptics and prior hospital and general practitioner visits. Prior hospital visits was the largest determinant. CONCLUSIONS: In our study we identified and confirmed the presence of known determinants for unplanned hospital admissions in community dwelling adults, most of which align with a geriatric phenotype. Our findings can inform the allocation of interventions aiming to reduce unplanned hospital admissions.

The impact of a pharmacist intervention on post-discharge hypnotic drug discontinuation in geriatric inpatients: a before-after study.

BACKGROUND: Chronic use of hypnotic agents is prevalent in older adults, who as a result are at increased risk for certain adverse events, such as day-time drowsiness and falls. Multiple strategies to discontinue hypnotics have been tested in geriatric patients, but evidence remains scarce. Hence, we aimed to investigate a multicomponent intervention to reduce hypnotic drug use in geriatric inpatients. METHODS: A before-after study was performed on the acute geriatric wards of a teaching hospital. The before group (= control group) received usual care, while intervention patients (= intervention group) were exposed to a pharmacist-led deprescribing intervention, comprising education of health care personnel, access to standardized discontinuation regimens, patient education and support of transitional care. The primary outcome was hypnotic drug discontinuation at one month after discharge. Secondary outcomes among others were sleep quality and hypnotic use at one and two weeks after enrolment and at discharge. Sleep quality was assessed using the Pittsburgh Sleep Quality Index (PSQI) upon inclusion, two weeks after enrolment and one month after discharge. Determinants for the primary outcome were identified using regression analysis. RESULTS: A total of 173 patients were enrolled, with 70.5% of patients taking benzodiazepines. Average age was 85 years (interquartile range 81-88.5) and 28.3% were male. A higher discontinuation rate at one month after discharge was observed in favour of the intervention (37.7% vs. 21.9%, p = 0.02281). No difference in sleep quality was found between both groups (p = 0.719). The average sleep quality was 8.74 (95% confidence interval (CI): 7.98-9.49) and 8.57 (95% CI: 7.75-9.39) in the control and intervention groups respectively. Determinants for discontinuation at one month were: the intervention (odds ratio (OR) 2.36, 95% CI: 1.14-4.99), fall on admission (OR 2.05; 95% CI: 0.95-4.43), use of a z-drug (OR 0.54, 95% CI: 0.23-1.22), PSQI score on admission (OR 1.08, 95% CI: 0.97-1.19) and discontinuation prior to discharge (OR 4.71, 95% CI: 2.26-10.17). CONCLUSIONS: A pharmacist-led intervention in geriatric inpatients was associated with a reduction of hypnotic drug use one month after discharge, without any loss in sleep quality. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT05521971 (retrospectively registered on 29th of August 2022).

Guideline-Directed Medical Therapies for Heart Failure with a Reduced Ejection Fraction in Older Adults: A Narrative Review on Efficacy, Safety and Timeliness.

Heart failure is a prevalent syndrome among older adults, with a major impact on morbidity and mortality. Higher age is correlated with underuse of guideline-directed medical therapies which, in turn, has been linked to worse clinical outcomes. Importantly, most evidence so far has been collected in adults who were younger, less multi-morbid and polymedicated compared with those who are commonly treated in daily clinical practice. Hence, we aimed to assess and describe the evidence base for pharmacotherapy in older adults with heart failure with a reduced ejection. First, a narrative review was undertaken using Medline, from inception to January 2023. Four foundational therapies were selected based on the latest European Society of Cardiology clinical practice guideline: angiotensin-converting enzyme inhibitors/angiotensin receptor neprilysin inhibitors, beta blockers, mineralocorticoid receptor antagonists and sodium-glucose cotransporter-2 inhibitors. Post hoc analyses from landmark heart failure drug trials were searched and included if they contained data on the impact of age on efficacy, safety and/or timeliness of therapies in the management of heart failure with a reduced ejection fraction. Second, a proposal was developed to support and promote the use of evidence-based heart failure pharmacotherapy in complex, older adults. In total, 11 articles were selected: 4 meta-analyses, 6 post hoc analyses and 1 review paper. No attenuation of efficacy for any of the foundational agents was found in older adults. Regarding safety, dedicated analyses showed that beta blockers, mineraloid receptor antagonists, sacubitril-valsartan, dapagliflozin and empagliflozin retained their overall benefit-risk profile regardless of age. Time to benefit was short and occurred generally within 1 month. Consensus was achieved on a five-step proposal to manage complex medication regimens in older adults suffering from heart failure. In conclusion, older adults suffering from heart failure with a reduced ejection fraction should not be denied treatment based on their age.

Community pharmacists' perceptions on multidisciplinary heart failure care: an exploratory qualitative study.

BACKGROUND: Heart failure (HF) is an important health problem and guidelines recommend multidisciplinary management. The pharmacist is an important member of the multidisciplinary heart failure team, both in the hospital and community setting. This study aims to explore the perceptions of community pharmacists on their role in HF care. METHODS: We conducted a qualitative study based on face-to-face semi-structured interviews with 13 Belgian community pharmacists between September 2020 and December 2020. We used the Qualitative Analysis Guide of Leuven (QUAGOL) method as guidance for data analysis until data saturation was reached. We structured interview content into a thematic matrix. RESULTS: We identified two major themes: heart failure management and multidisciplinary management. Pharmacists feel responsible for the pharmacological and non-pharmacological management of heart failure, citing easy access and pharmacological expertise as important assets. Diagnostic uncertainty, lack of knowledge and time, disease complexity and difficulties in communication with patients and informal care providers are barriers to optimal management. General practitioners are the most important partners in multidisciplinary community heart failure management, although pharmacists perceive a lack of appreciation and cooperation and deplore communication difficulties. They feel intrinsically motivated to provide extended pharmaceutical care in HF but cite the lack of financial viability and information sharing structures as important barriers. CONCLUSION: The importance of pharmacist involvement in multidisciplinary heart failure teams is undisputed by Belgian pharmacists, who cite easy access and pharmacological expertise as important assets. They point out several barriers impeding evidence-based pharmacist care for outpatients with heart failure: diagnostic uncertainty and disease complexity, lack of multidisciplinary information technology and insufficient resources. We recommend that future policy should focus on improved medical data exchanges between primary and secondary care electronic health records as well as the reinforcement of interprofessional relationships between locally affiliated pharmacists and general practitioners.

Pharmacokinetic drug-drug interactions with direct anticoagulants in the management of cancer-associated thrombosis.

Drug-drug interactions (DDIs) are common in cancer management and complicate the choice of anticoagulation in cancer-associated thrombosis. Cancer confers an increased risk of thrombotic events. Also, more bleeding events are observed in those who receive anticoagulation compared to those without cancer. In the treatment of cancer-associated thrombosis, direct oral anticoagulants (DOACs) have been found to be at least as effective as low-molecular weight heparins, which became the standard of care after several trials demonstrated superiority over vitamin K antagonists. Non-inferiority compared to low-molecular weight heparins has been shown for rivaroxaban, edoxaban and apixaban with a signal of fewer recurrent thrombotic events, albeit with an increase in bleeding events. Yet, potentially major pharmacokinetic drug-drug interactions have been identified as a reason to withhold DOACs and to rather choose an alternative. Practical guidance on what constitutes a major pharmacokinetic interaction and/or how to deal with these interactions in clinical practice is limited. Hence, here we have provided a framework to allow clinicians to better deal with pharmacokinetic drug-drug interactions between DOACs and cancer therapies in the management of cancer-associated thrombosis. In this review we have discussed the current literature, how the pharmacokinetic profile links to the label information on DDI, and have provided a practical proposal, applied to a clinical case.

Insights into the Pharmacokinetics and Pharmacodynamics of Direct Oral Anticoagulants in Older Adults with Atrial Fibrillation: A Structured Narrative Review.

Older adults, the fastest growing population, represent almost 50% of all users of direct oral anticoagulants (DOACs). Unfortunately, we have very little relevant pharmacological and clinical data on DOACs, especially in older adults with geriatric profiles. This is highly relevant as pharmacokinetics and pharmacodynamics (PK/PD) often differ substantially in this population. Hence, we need to obtain a better understanding of the PK/PD of DOACs in older adults, to ensure appropriate treatment. This review summarises the current insights into PK/PD of DOACs in older adults. A search was undertaken up to October 2022 to identify PK/PD studies of apixaban, dabigatran, edoxaban, and rivaroxaban, that included older adults aged ≥ 75 years. This review identified 44 articles. Older age alone did not influence exposure of edoxaban, rivaroxaban and dabigatran, while apixaban peak concentrations were 40% higher in older adults than in young volunteers. Nevertheless, high interindividual variability in DOAC exposure in older adults was noted, which can be explained by distinctive older patient characteristics, such as kidney function, changes in body composition (especially reduced muscle mass), and co-medication with P-gp inhibitors, which is in line with the current dosing reduction criteria of apixaban, edoxaban, and rivaroxaban. Dabigatran had the largest interindividual variability among all DOACs since its dose adjustment criterion is only age, and thus it is not a preferable option. Additionally, DOAC exposure, which fell outside of on-therapy ranges, was significantly related to stroke and bleeding events. No definite thresholds linked to these outcomes in older adults have been established.

Should vericiguat be initiated in geriatric inpatients with heart failure with reduced ejection fraction and a worsening heart failure event prior to discharge?

Heart failure (HF) occurs predominantly in older adults. HF patients have an increased risk for an acute exacerbation, which commonly requires hospitalisation. Such a worsening HF (WHF) event has an impact on prognosis. Vericiguat is a novel agent which has been shown to reduce the HF hospitalisation risk in patients with a recent WHF event. It is not fully clear how to position this novel agent in geriatric HF inpatients.

Age is just a number: the concept of time to benefit in older adults.

A female nursing home resident aged >70 years was admitted to the geriatric ward with de novo dysphagia 6 days after being discharged from the stroke unit. Metformin and ezetimibe had been added to her treatment regimen which already consisted of clopidogrel, atorvastatin, denosumab, calcium and vitamin D. At the geriatric ward a multidisciplinary team involving clinical pharmacists reviewed all treatments and appraised the time to benefit, ascertaining whether there was sufficient time left to experience therapeutic benefits. As a result, metformin, ezetimibe, denosumab, calcium and vitamin D were discontinued. This case report illustrates that both mortality risk assessment and evaluation of the time to benefit should be part of any medication review in frail older adults. Conversely, with limited available data pertaining to the concept of time to benefit, we advocate a broader awareness among pharmacists and a systematic assessment in future clinical trials.