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Cardiovascular diseases are the main causes of death, and statins can reduce the risk of major vascular events. Lithuania is among the European countries with the highest cardiovascular mortality despite a rapidly increasing use of statins. Previous reviews have shown the problem of poor patient adherence, but there are limited studies from Eastern European countries. The aim of this study was to evaluate treatment persistence in new users of statins in Lithuania and to investigate factors associated with persistence. Dispensed prescriptions from patients aged >18 years old initiated on statins in 2018-2019 were included, and data were obtained from a national health insurance fund. Persistence was assessed by the proportion of patients who still had statins dispensed 1 year after the first dispensing. Factors associated with persistence were assessed using logistic regression. A total of 104 726 patients (41.3% men) were initiated on statin treatment. Only 41% of them continued statin use 1 year after initiation. Factors associated with higher persistence rate were older age, higher dose of statin, use of other medicines and use of statins as secondary prevention. Low persistence to statin therapy needs to be recognized by healthcare workers, pharmacists and policy makers to address this problem., (© 2024 The Authors. Basic & Clinical Pharmacology & Toxicology published by John Wiley & Sons Ltd on behalf of Nordic Association for the Publication of BCPT (former Nordic Pharmacological Society).)

Purpose: Hypertension is an important risk factor for severe outcomes in patients with COVID-19, and antihypertensive drugs may have a protective effect. However, the pandemic may have negatively impacted health care services for chronic diseases. The aim of this study was to assess initiations of antihypertensive medicines in patients infected by COVID-19., Methods: A cohort study including all Swedish residents 20-80 years old with a COVID-19 positive test compared with an unexposed group without COVID-19 matched for age, sex, and index date (date of confirmed COVID-19). Data were collected within SCIFI-PEARL, a study including linked data on COVID tests, hospital diagnoses, dispensed prescriptions, and socioeconomic data from Swedish national registers. Initiations of different antihypertensive drugs were studied from March 2020 until October 2020. Associations between COVID-19 and initiation of antihypertensives were assessed by a multivariable Cox proportional hazards model., Results: A total of 224 582 patients (exposed and unexposed) were included. After adjusting for cardiovascular comorbidities and education level, ACEi was the most commonly initiated antihypertensive agent to patients with COVID-19. Hazard ratio and 95% confidence interval for initiation of drug therapy was 1.83 [1.53-2.19] for ACEi, followed by beta-blockers 1.74 [1.55-1.95], calcium channel blockers 1.61 [1.41-1.83], angiotensin receptor blockers 1.61 [1.40-1.86], and diuretics 1.53 [1.32-1.77]., Conclusion: All antihypertensive medicines were initiated more frequently in COVID-19 patients. This can either be associated with hypertension caused by the COVID-19 infection, more frequent diagnosis of hypertension among people with COVID-19 since they consult health care, or residual confounding factors not adjusted for in the study., (© 2022 The Authors. Basic & Clinical Pharmacology & Toxicology published by John Wiley & Sons Ltd on behalf of Nordic Association for the Publication of BCPT (former Nordic Pharmacological Society).)

Evidence-based recommendations for choice of antiepileptic drug (AED) in post-stroke epilepsy (PSE) are lacking. The aim of this study was to describe the use and persistence of AEDs when initiating treatment in men and women with PSE. An observational study based on individual-level patient data from a regional healthcare register in Stockholm, Sweden, was conducted. Adults (≥18 years) with a stroke diagnosis 2012-2016, a dispensed prescription of any AED within two years after the stroke, and with an epilepsy-related diagnosis were identified. Multinomial logistic regression and logistic regression were used to identify factors associated with choice of AED and discontinuation within 90 days, respectively. Of 9652 men and 9844 women with a stroke diagnosis, 287 men and 273 women had PSE and were dispensed AED. More than 60% of both men and women with PSE were treated with levetiracetam. Carbamazepine was the second most common drug followed by lamotrigine and valproic acid. There were significant differences in AED choice depending on for instance sex, age and renal impairment. Levetiracetam had the highest persistence in both men and women. Choice of AED, oral anticoagulant use and percutaneous endoscopic gastrostomy (PEG) showed an association with the persistence to therapy. We conclude that in both men and women with PSE, levetiracetam was the most used AED for initiation of treatment and also had the highest persistence., (© 2021 The Authors. Basic & Clinical Pharmacology & Toxicology published by John Wiley & Sons Ltd on behalf of Nordic Association for the Publication of BCPT (former Nordic Pharmacological Society).)

In 2016, all prescription drugs included in the reimbursement system in Sweden were made available for children (age 0-17 years) without any patient fees. Our aim was to estimate the association between this intervention and the dispensing patterns of asthma medications among children. Dispensing data on asthma medications for all children living in Stockholm County during 2014-2017 were selected to include two years before (January 2014-December 2015) and after (January 2016-December 2017) the intervention. In an uncontrolled before and after study, the measures of utilization were as follows: the proportion of children with at least one dispensed asthma medication (prevalence); the number of children initiated on treatment after an 18-month drug-free period (incidence); the number of defined daily doses (DDDs) dispensed per child; and the number of children with at least two prescriptions with controller medication (inhaled corticosteroid or leukotriene receptor antagonist) dispensed during 18 months (persistence). In an interrupted time series (ITS) analysis, all measures were included except for persistence. Socio-economic status was defined using Mosaic data. The prevalence increased after the intervention (from 11.9% to 13.0%). However, the ITS analysis showed a positive trend already before the intervention, and consequently, the increase was not attributable to the intervention. For incidence, similar patterns were observed. There was an increase in dispensed volumes related to the intervention, 46.3 DDDs/child/month before and 51.1 after the intervention (P-value 0.01). The proportion of children with persistent asthma medication increased from 46.0% to 51.9% in children with low socio-economic status. In conclusion, the intervention was only modestly associated with changes in the dispensing patterns of asthma medication, with the volume dispensed per child increasing slightly, particularly in children with low socio-economic status., (© 2019 Nordic Association for the Publication of BCPT (former Nordic Pharmacological Society).)

The aim of this population-based, cross-sectional study was to analyse the prevalence of renally inappropriate medicines (RIMs) in older people with renal impairment. We included 30 372 people aged ≥65 years with chronic kidney disease (CKD) stage 3, and 2161 with stage 4 attending primary care in Stockholm, Sweden. We used data derived from SCREAM, a database linking patient-specific data on demography, morbidity, healthcare consumption and dispensed drugs to creatinine measurements. Estimated glomerular filtration rate was calculated with CKD-EPI based on the first non-hospital serum creatinine in 2010. RIMs were defined as medicines needing dose adjustment or being contra-indicated in CKD stage 3 or 4 with reference to Swedish "Janusmed Drugs and Renal function." Dispensed prescription drugs were analysed during 1 year after creatinine assessment. Drug doses were considered as excessive if their mean volume dispensed per day exceeded the recommended dose. Contra-indicated medicines were regarded as inappropriate if dispensed at least once during 1 year. Excessive dosing was present in 42.5% of older people with CKD stage 3 and in 58.1% with stage 4. The prevalence of contra-indicated medicines was 9.4% and 38.0%, respectively. A limited number of RIMs accounted for the majority of excessive dosing, such as drugs acting on the renin-angiotensin-aldosterone system, betablockers and opioids. Commonly dispensed contra-indicated substances were NSAIDs and antidiabetics. We conclude that the prevalence of RIMs in older people with renal impairment is considerably high. Still, RIM use may be manageable as only a limited number of RIMs are frequently used., (© 2018 Nordic Association for the Publication of BCPT (former Nordic Pharmacological Society).)

Although continued use of antidepressants (AD) has been found to be associated with a lower risk of suicide, AD discontinuation is reported repeatedly. The aim of this case-control study, thus, was to assess whether discontinuation to AD was associated with an increased risk of suicide, according to different genders and age groups. The Social and Health Information System of Friuli Venezia Giulia Region, Italy, was used to collect data on suicides, diagnoses and AD use from 2005 to 2014. We selected, as cases, all suicides that had at least one prescription of AD in the 730 days before death (N = 876), and we matched with regard to age and sex each case with five controls from the general population. Conditional logistic regression analyses were used to assess the association between suicide and modifications of AD treatment. We found that 70% of suicides and controls from the general population discontinued AD in the 2 years before the index date. In two-thirds of them, discontinuations were two or more. Discontinuation of AD, however, did not represent a significant risk factor for suicide. More appropriate care of depression, particularly by primary care physicians who widely prescribe AD, should be fostered in order to prevent suicide. However, more research is needed to assess to which extent AD discontinuation can affect suicidal risk., (© 2018 Nordic Association for the Publication of BCPT (former Nordic Pharmacological Society).)

Aim: To explore the feasibility of the electronic assessment of potentially inappropriate medication (PIM) criteria in a large administrative database and to explore the validity of the cardiovascular subset of PIM criteria, by studying the association with relevant outcome., Method: A cohort study using administrative data from Stockholm County, Sweden (VAL database). Eligible for inclusion were community-dwelling older people (≥65 years), alive in Stockholm County on 31 December 2015. We applied PIM criteria pertaining to the cardiovascular medication group (first-level ATC C group), and we assessed the association between PIM use and mortality and hospitalisation., Results: Patients' (n = 315 120) mean age was 74.0 years (range 65-114), and 54.7% were women. There were 111 cardiovascular PIM criteria in the repository, from which 44 were not registered or prescribed in our population. We excluded another 43 requiring information not available in the database, or duplicates, resulting in 24 applicable criteria. The prevalence of polypharmacy (≥ five medications) was 25.5% and the prevalence of at least one PIM use was 8.3%, including 2.8% underuse and 5.3% misuse. Patients with intake of ≥10 medications had 38% increased mortality risk compared to those with 0-4 medications. Unplanned hospitalisation and emergency department visits were positively associated with underuse (12% and 25%, respectively) and misuse (13% and 12%, respectively)., Conclusion: It was feasible to select a subset of cardiovascular PIM criteria originating from different PIM lists and to apply this subset in an administrative database. Additionally, by applying this subset, we showed significant associations with clinical outcome., (© 2018 Nordic Association for the Publication of BCPT (former Nordic Pharmacological Society).)

This study aimed to investigate the utilization of antiepileptic drugs (AEDs) in children and adolescents with epilepsy and other diagnoses in a nationwide population between 2007 and 2014. Data on dispensed prescriptions of AEDs were collected from the Swedish Prescribed Drug Register and linked to diagnosis data from the National Patient Register covering all in- and outpatient consultations from Swedish hospitals. Children aged 0-17 years who had received at least one prescription for AEDs were selected. We calculated proportions of patients stratified by indication, sex and type of AED. A total of 18,131 patients (mean age 9.5 years, 50% boys) were initiated on AED treatment between January 2007 and December 2014. Epilepsy was the most frequent diagnosis (46%) recorded within the year prior to the first AED dispensing. Psychiatric and pain diagnoses were more common in girls (sex distribution 70/30 and 59/41, respectively). In epilepsy, the most frequently initiated AED was valproic acid in boys and lamotrigine in girls. Lamotrigine was the most frequently initiated drug in psychiatry, in both boys and girls. This nationwide study provides new knowledge on AED use in children and adolescents. The use of AEDs during the study period was mainly restricted to epilepsy, and the individual AEDs used seems to be in accordance with approved indications. However, the use of AED on non-epilepsy diagnoses, especially pain disorders, raises concerns., (© 2018 Nordic Association for the Publication of BCPT (former Nordic Pharmacological Society).)

The aim of this study was to quantify and characterize the scientific output from the Swedish Prescribed Drug Register (SPDR) the first decade after its establishment. A systematic literature search was performed in Medline, EMBASE and PubMed (2005-2014). Additional publications were identified by personal knowledge, reference lists, contact with active authors and a citation search in Web of Sciences. Publications using SPDR data were included in the analysis and characterized regarding study type, presence of patient-level record linkage, target population and topic. A total of 719 publications were identified in the literature search and an additional 148 by other strategies. Three hundred and thirty-eight studies fulfilled the inclusion criteria. The majority were analytic (n = 166; 49.1%) or descriptive (n = 100; 29.5%). The remaining studies focused on validation (n = 20; 5.9%), health economics (n = 16; 4.7%) or miscellaneous (n = 36; 10.7%). The analytic studies investigating effects of drug exposure focused mainly on safety (n = 46) and/or effectiveness (n = 24). The first publications appeared in 2007 (n = 6), and in 2014, 90 articles using SPDR were published. Over the years, linkage with other registers using the personal identity number increased (0-88.9% of the publications). The population was often selected by age (49.7%), condition (45.0%) and/or drug (22.8%) and concerned predominantly psychiatric (29.0%) and cardiovascular (20.4%) diseases. In conclusion, this study illustrates that the establishment of a nationwide individual-based register on dispensed prescription drugs facilitates an encouraging development of pharmacoepidemiological research, both regarding the number of publications and the scientific level of the analyses., (© 2016 The Authors. Basic & Clinical Pharmacology & Toxicology published by John Wiley & Sons Ltd on behalf of Nordic Association for the Publication of BCPT (former Nordic Pharmacological Society).)

Quality indicators are increasingly used as a tool to achieve safe and quality clinical care, cost-effective therapy, for professional learning, remuneration, accreditation and financial incentives. A substantial number focus on drug therapy but few address the introduction of new medicines even though this is a burning issue. The objective was to describe the issues and challenges in designing and implementing a transparent indicator framework and evaluation protocol for the introduction of new medicines and to provide guidance on how to apply quality indicators in the managed entry of new medicines. Quality indicators need to be developed early to assess whether new medicines are introduced appropriately. A number of key factors need to be addressed when developing, applying and evaluating indicators including dimensions of quality, suggested testing protocols, potential data sources, key implementation factors such as intended and unintended consequences, budget impact and cost-effectiveness, assuring the involvement of the medical professions, patients and the public, and reliable and easy-to-use computerized tools for data collection and management. Transparent approaches include the need for any quality indicators developed to handle conflict of interests to enhance their validity and acceptance. The suggested framework and indicator testing protocol may be useful in assessing the applicability of indicators for new medicines and may be adapted to healthcare settings worldwide. The suggestions build on existing literature to create a field testing methodology that can be used to produce country-specific quality indicators for new medicines as well as a cross international approach to facilitate access to new medicines., (© 2014 Nordic Association for the Publication of BCPT (former Nordic Pharmacological Society).)

There is limited experience and methods for extractions of drug therapy data from electronic health records (EHR) in the hospital setting. We have therefore developed and evaluated completeness and consistency of an automatic versus a semi-automatic extraction procedure applied on prescribing and administration of the TNF inhibitor infliximab using a hospital EHR system in Karolinska University Hospital, Sweden. Using two different extraction methods (automatic and semi-automatic), all administered infusions of infliximab between 2007 and 2010 were extracted from a database linked to the EHR system. Extracted data included encrypted personal identity number (PIN), date of birth, sex, time of prescription/administration, healthcare units, prescribed/administered dose and time of admission/discharge. The primary diagnosis (ICD-10) for the treatment with infliximab was extracted by linking infliximab infusions to their corresponding treatment episode. A total of 13,590 infusions of infliximab were administered during the period of 2007 to 2010. Of those were 13,531 (99.6%) possible to link to a corresponding treatment episode, and a primary diagnosis was extracted for 13,530 infusions. Information on encrypted PIN, date of birth, time of prescription/administration, time of admission/discharge and healthcare unit was complete. Information about sex was missing in one patient only. Calculable information about dosage was extracted for 13,300 (98.3%) of all linked infusions. This methodological study showed the potential to extract drug therapy data in a hospital setting. The semi-automatic procedure produced an almost complete pattern of demographics, diagnoses and dosages for the treatment with infliximab., (© 2013 Nordic Pharmacological Society. Published by John Wiley & Sons Ltd.)

The aim was to present and evaluate the impact of a comprehensive strategy over 10 years to select, communicate and achieve adherence to essential drug recommendations (EDR) in ambulatory care in a metropolitan healthcare region. EDRs were issued and launched as a 'Wise List' by the regional Drug and Therapeutics Committee in Stockholm. This study presents the concept by: (i) documenting the process for selecting, communicating and monitoring the impact of the 'Wise List'; (ii) analysing the variation in the number of drug substances recommended between 2000 and 2010; (iii) assessing the attitudes to the 'Wise List' among prescribers and the public; (iv) evaluating the adherence to recommendations between 2003 and 2009. The 'Wise List' consistently contained 200 drug substances for treating common diseases. The drugs were selected based on their efficacy, safety, suitability and cost-effectiveness. The 'Wise List' was known among one-third of a surveyed sample of the public in 2002 after initial marketing campaigns. All surveyed prescribers knew about the concept and 81% found the recommendations trustworthy in 2005. Adherence to recommendations increased from 69% in 1999 to 77% in 2009. In primary care, adherence increased from 83% to 87% from 2003 to 2009. The coefficient of variation (CV%) decreased from 6.1% to 3.8% for 156 healthcare centres between these years. The acceptance of the 'Wise List' in terms of trust among physicians and among the public and increased adherence may be explained by clear criteria for drug recommendations, a comprehensive communication strategy, electronic access to recommendations, continuous medical education and involvement of professional networks and patients.

The Nordic countries have a long tradition of registry-based epidemiological research. Many population-based health registries were established in the 1960s, with use of unique personal identifiers facilitating linkage between registries. In recent years, each country has established a national database to track prescription drugs dispensed to individuals in ambulatory care. The objectives were to present an overview of the prescription databases established in the Nordic countries, as well as to elaborate on their unique potential for record linkage and cross-national comparison of drug utilization. Five Nordic countries collect drug exposure data based on drugs dispensed at pharmacies and have the potential to link these data to health outcomes. The databases together cover 25 million inhabitants (Denmark: 5.5 million; Finland: 5.3 million; Iceland: 0.3 million; Norway: 4.8 million; and Sweden: 9.2 million). In 2007, the registries encompassed 17 million prescription drug users (68% of the total population). We provide examples of how these databases have been used for descriptive drug utilization studies and analytical pharmacoepidemiological studies linking drug exposure to other health registries. Comparisons are facilitated by many similarities among the databases, including data source, content, coverage and methods used for drug utilization studies and record linkage. There are, however, some differences in coding systems and validity, as well as in some access and technical issues. To perform cross-national pharmacoepidemiological studies, resources, networks and time are needed, as well as methods for pooling data. Interpretation of results needs to account for inter-country heterogeneity and the possibility of spurious relationships. The Nordic countries have a unique potential for collaborative high-quality cross-national pharmacoepidemiological studies with large populations. This research may assist in resolving safety issues of international interest, thus minimizing the risk of either over-reacting on possible signals or underestimating drug safety issues.