Reimbursement and use of oral anticoagulants during 2014-2022 - A register-based study.

Background: Vitamin K antagonists, warfarin in particular, have been the mainstay of anticoagulation therapy, but their use has declined in many countries since direct oral anticoagulants (DOACs) have entered the market. Objective: To examine utilization trends of oral anticoagulants (OACs) in Finland considering the reimbursement of DOACs and changes to national treatment guidelines for the treatment of atrial fibrillation (AF). Methods: Both public, aggregated data on reimbursed OAC dispensations and individual-level data on electronic dispensations during 2014-2022 were applied. Data on electronic dispensations during 2015-2016 were used to study OAC initiations. Data on entitlements to reimbursement for DOACs came from public data. Results: In 2014, there were almost 20,000 DOAC users, rising to 214,000 in 2022. The number of warfarin users declined since 2015 from over 181,000 to around 59,000 users in 2022, DOACs exceeding warfarin in the number of users in 2019. The total DOAC costs were higher than warfarin costs each year. Rivaroxaban was the most widely used DOAC during 2014-2018, and apixaban during 2019-2022. In 2015, there were more warfarin (56.7%) than DOAC (43.3%) initiators, but the result was opposite for 2016 (warfarin 39.4%, DOACs 60.6%). The number of individuals entitled to reimbursement for DOACs has increased steadily, and in 2022, there were over 196,000 individuals entitled to this reimbursement due to AF. Conclusions: The uptake of DOACs in Finland appears to have been gradual and slower than in many other countries. During the 2010s, the treatment guidelines for AF were more cautious in recommending DOACs than the European guidelines. The use of DOACs increased as their reimbursement became less restrictive.

Success and failure factors of patient recruitment for industry-sponsored clinical trials and the role of the electronic health records-a qualitative interview study in the Nordic countries.

BACKGROUND: Patient recruitment for clinical trials is challenging-only approximately one third of all trials recruit their participants as planned. The pharmaceutical industry's views on recruitment success have not been comprehensively investigated, although the industry globally conducts almost one third of all clinical drug trials. This study explored patient recruitment success and failure factors and the role of electronic health records (EHR) in the recruitment of trial participants in the Nordic countries. METHODS: A descriptive qualitative interview study was conducted with 21 representatives of the pharmaceutical industry or contract research organizations operating in Finland, Sweden, Denmark, and Norway. The interviews covered 34 clinical pre-market drug trials. Qualitative data were analyzed using inductive content analysis. RESULTS: Four main categories were derived to represent both success and failure factors, whereas a fifth category represented only failure factors: (1) sponsor-related (protocol and trial preparation and feasibility evaluations), (2) site/investigator-related (access to patients, motivation, commitment and resources), (3) patient-related recruitment factors (medical need, patients' role in their care and attitudes towards trials), (4) Sponsor-sites-patients collaboration factors, and (5) start-up related factors. EHR was the most important source of recruitment, utilized in 29 out of 34 trials discussed. Revision of the legislation regulating the secondary use of EHR was highlighted as the most effective measure to facilitate the use of EHR in recruitment of trial participants. CONCLUSIONS: The industry representatives recognized quite well their own role in contributing to the success or failure of the recruitment: to facilitate recruitment of trial participants, many obstacles can be avoided with better trial preparation and proper feasibility evaluations. As access to patients represents one of the key success or failure factors of recruitment, and as the EHR is regarded the main source of searching for and finding patients, the development of EHR utilization appears to represent a powerful tool to improve patient recruitment.

Clinical trial site identification practices and the use of electronic health records in feasibility evaluations: An interview study in the Nordic countries.

INTRODUCTION: Feasibility evaluations are performed to create the best possible starting point for the set-up and execution of a clinical trial, and to identify any obstacles for successful trial conduct. New digital technologies can provide various types of data for use in feasibility evaluations. There is a need to identify and compare such data sources for trial site identification and for evaluating the sites' patient recruitment potential. Especially, information is needed on the use of electronic health records. We investigated how different data sources are used by pharmaceutical companies operating in the Nordic countries for identifying trial sites and for evaluating their potential to recruit trial participants. METHODS: This was a semi-structured qualitative interview study with 21 participants from pharmaceutical companies and contract research organizations operating in Finland, Sweden, Denmark and Norway. Qualitative content analysis was applied. RESULTS: For identifying countries and trial sites on a global level, the trial sponsors mostly used databases on previous trial performance. The use of electronic health record data was very limited. Sites' and investigators' visibility in various databases was seen as fundamental for their countries becoming selected into new clinical trials. For estimating the sites' recruitment projections, most sites were seen to base their patient count estimates solely on their previous experience. Some sites had reviewed their electronic health record data, which was considered to increase the accuracy of their recruitment estimates and these sites' attractivity. Along with dialogs with investigators, the sponsors used various data sources to validate the investigators' estimates. Legislative obstacles were seen to hinder the use of electronic health record queries for estimation of patient counts. CONCLUSION: Visibility in the databases used by trial sponsors is crucial for the countries and sites to be identified. Site selection appears to be based on trust and relationships built from experience, but electronic data provide the support upon which the trust is based. Estimation of the number of potential trial participants is a complex and time-consuming process for both investigators and sponsors. Sponsors seem to favour sites who could support their patient count estimates with electronic health record data as they were quicker in providing the estimates and more reliable than sites with no electronic health record evidence. The patient count evaluation process could be simplified, accelerated and made more reliable with more systematic use of electronic health record evidence in the feasibility evaluation phase. This would increase the accuracy of the patient count estimates and, on its part, contribute to improved recruitment success.

Assessing an Electronic Health Record research platform for identification of clinical trial participants.

Electronic health records (EHR) are a potential resource for identification of clinical trial participants. We evaluated how accurately a commercially available EHR Research Platform, InSite, is able to identify potential trial participants from the EHR system of a large tertiary care hospital. Patient counts were compared with results obtained in a conventional manual search performed for a reference study that investigated the associations of atrial fibrillation (AF) and cerebrovascular incidents. The Clinical Data Warehouse (CDW) of Turku University Hospital was used to verify the capabilities of the EHR Research Platform. The EHR query resulted in a larger patient count than the manual query (EHR Research Platform 5859 patients, manual selection 2166 patients). This was due to the different search logic and some exclusion criteria that were not addressable in structured digital format. The EHR Research Platform (5859 patients) and the CDW search (5840 patients) employed the same search logic. The temporal relationship between the two diagnoses could be identified when they were available in structured format and the time difference was longer than a single hospital visit. Searching for patients with the EHR Research Platform can help to identify potential trial participants from a hospital's EHR system by limiting the number of records to be manually reviewed. EHR query tools can best be utilized in trials where the selection criteria are expressed in structured digital format.

Frailty and Co-Prescribing of Potentially Interacting Drugs in New Users of Warfarin.

BACKGROUND: Warfarin is underutilised in frail older people because of the fear of bleeding complications. Drug interactions are an independent bleeding risk factor. However, the extent to which potential drug interactions are taken into account at warfarin therapy initiation in frail patients is not known. OBJECTIVE: The objective of this study was to investigate the use of potentially interacting drugs increasing the bleeding risk before and after warfarin initiation in frail and non-frail patients. METHODS: We conducted an observational study including inpatients aged ≥ 60 years initiated on warfarin in a tertiary hospital in Adelaide, South Australia. Frailty status was assessed with the Reported Edmonton Frail Scale. Medication charts were reviewed before and after warfarin initiation. RESULTS: In total, 151 patients (102 non-frail and 49 frail) were included. Before warfarin initiation, the use of clopidogrel and acetaminophen was more common in frail patients compared with non-frail patients (25.5% vs 10.2%, p = 0.0135, 63.8% vs 35.7% p = 0.0014, respectively). The use of non-steroidal anti-inflammatory drugs, 9.2% in non-frail patients and 6.4% in frail patients before warfarin initiation, was completely stopped after warfarin initiation in both groups. The use of antiplatelet drugs decreased from 56.1% in non-frail patients and 66.0 % in frail patients to 12.2% and 14.9%, respectively. Instead, the use of drugs affecting the metabolism of warfarin or vitamin K increased in both groups. No statistically significant difference was seen in the exposure to interacting drugs between study groups after warfarin initiation. Acetaminophen, senna glycosides and cytochrome P450 2C9 inhibiting drugs were the most common interacting drugs at discharge used in 49.0%, 18.4% and 20.4% of non-frail patients and 53.2%, 29.8% and 19.1% of frail patients, respectively. CONCLUSIONS: The overall frequency of potential drug interactions was moderate and frail patients were not exposed to warfarin drug interactions more often than non-frail patients. Further studies in larger study populations are required to verify these results.

First insight to the Finnish nationwide electronic prescription database as a data source for pharmacoepidemiology research.

BACKGROUND: Since 1994, the Finnish Prescription Register (FPR) has been the main data source for pharmacoepidemiology research in Finland. However, the FPR data are limited to reimbursed dispensations only. Implementation of electronic prescribing started in 2010 and after a stepwise extension, electronic prescribing became mandatory in all healthcare settings in 2017. Prescriptions issued and dispensed electronically are stored in the Prescription Centre of the nationwide Kanta database. OBJECTIVES: To describe the contents of the Kanta database and to compare the coverage of Kanta with the FPR, using prescriptions and dispensations of oral anticoagulants (OACs) as an example. METHODS: All prescriptions, dispensations, and their cancellations and corrections for OACs recorded in Kanta were retrieved for the period 2012-2016. RESULTS: In 2016, the total number of valid electronic prescriptions for OACs was 249 139 and the number of valid electronic OAC dispensations was 765 745. The number of identified direct oral anticoagulant (DOAC) users was higher in Kanta compared to the FPR since 2014, although more users of all OACs were identified from the FPR during 2012-2015. In 2016, an indication was identified in 44.7% of OAC prescriptions and dosing instructions in 99.5% of DOAC prescriptions. CONCLUSIONS: The Kanta database is a promising source of data on medication exposure. Because of reimbursement restrictions, use of DOACs was under-ascertained through the FPR.

Physicians' views on patient participation in choice of oral anticoagulants in atrial fibrillation-a qualitative study.

Direct oral anticoagulants provide an alternative to vitamin K antagonists for the anticoagulation therapy in atrial fibrillation (AF). The availability of several treatment options with different attributes makes shared decision-making appropriate for the choice of anticoagulation therapy. The aim of this study was to understand how physicians choose an oral anticoagulant (OAC) for patients with AF and how physicians view patients' participation in this decision. Semi-structured interviews with 17 Finnish physicians (eight general practitioners and nine specialists) working in the public sector were conducted. An interview guide on experience, prescribing and opinions about oral anticoagulants was developed based on previous literature. The data were thematically analysed using deductive and inductive approaches. Based on the interviews, patient's opinion was the most influential factor in decision-making when there were no clinical factors limiting the choice between OACs. Of patient's preferences, the most important was the attitude towards co-payments of OACs. Patients' opinions on monitoring of treatment, dosing and antidote availability were also mentioned by the interviewees. The choice of an OAC in AF was patient-centred as all interviewees expressed that patient's opinion affects the choice.

Statins do not Increase the Rate of Bleeding Among Warfarin Users.

Clinical significance of potential interaction between warfarin and statins is unclear. Our objective was to determine whether use of statins as a class or use of simvastatin modulates the rate of bleeding requiring hospitalization among new warfarin users. Using Finnish healthcare databases, we identified a cohort of 101,588 warfarin initiators between 1 January 2009 and 30 June 2012. By the end of 2012, these patients accumulated 92,695 person-years of exposure to warfarin-only and 60,253 years of exposure to warfarin-with-statin. The outcome was a composite of gastrointestinal, intracranial or other bleeding leading to hospitalization. A Poisson generalized estimating equation model was employed to estimate rate ratios (RR) and their 95% confidence intervals (CI) for exposure to warfarin-with-statin compared to warfarin-only and to allow multiple episodes per patient and time-dependent covariates. In multivariable models, we found no difference in the bleeding rate in association with exposure to any statin (multivariable-adjusted RR = 0.98, 95% CI 0.89-1.07) or to simvastatin (RR = 1.01, 95% CI 0.91-1.11) with warfarin compared to exposure to warfarin-only. We conclude that concomitant use of statins and warfarin was not associated with an increased rate of bleeding requiring hospitalization.

Low serum adiponectin levels in childhood and adolescence predict increased intima-media thickness in adulthood. The Cardiovascular Risk in Young Finns Study.

INTRODUCTION: Low adiponectin levels may predict the development of atherosclerosis. We examined the association of childhood adiponectin with preclinical carotid atherosclerosis that is defined as plaque and/or high (≥95th percentile) intima-media thickness (IMT) at the carotid bifurcation in adulthood. METHODS: The Cardiovascular Risk in Young Finns Study is a cohort study on cardiovascular risk factors. We used risk factor data from the baseline study (1980) and ultrasound findings from the follow-ups (2001 and 2007). The study population included 1708 participants, aged 3-18 years at baseline. RESULTS: In multivariate analysis, childhood adiponectin was inversely associated with preclinical carotid atherosclerosis: odds ratio 0.68, 95% confidence interval (CI) 0.53-0.86, p = .001, for 1-SD increase in childhood adiponectin after adjusting for childhood non-high-density lipoprotein cholesterol, body mass index, and blood pressure. When examining the incremental predictive ability, we observed that compared to an approach utilizing only conventional risk factors, the model additionally including adiponectin levels improved c-statistics area under curve from 0.733 (95% Cl 0.694-0.771) to 0.748 (95% Cl 0.710-0.786), p = .02. CONCLUSIONS: Childhood adiponectin levels improve the prediction of carotid atherosclerosis in adulthood over conventional risk factors. This supports the idea that low adiponectin levels may have a role in the development of preclinical atherosclerosis. Key messages Childhood adiponectin levels improve the prediction of increased carotid intima-media thickness in adulthood over conventional cardiovascular risk factors. These results suggest that adiponectin levels measured in childhood may have a role in the atherosclerotic process.

Socioeconomic Inequalities in Statin Adherence Under Universal Coverage: Does Sex Matter?

BACKGROUND: Previous research shows that low socioeconomic position (SEP; especially low income) is associated with statin nonadherence. We investigated the relationship between SEP and statin adherence in a country with universal coverage using group-based trajectory modeling in addition to the proportion of days covered. METHODS AND RESULTS: Using data from Finnish healthcare registers, we identified 116 846 individuals, aged 45 to 75 years, who initiated statin therapy for primary prevention of cardiovascular disease. We measured adherence as proportion of days covered over an 18-month period since initiation and identified different adherence patterns based on monthly adherence with group-based trajectory modeling. When adjusted for age, marital status, residential area, clinical characteristics, and copayment, low SEP was associated with statin nonadherence (proportion of days covered <80%) among men (eg, lowest versus highest income quintile: odds ratio, 1.41; 95% confidence interval, 1.32-1.50; basic versus higher-degree education: odds ratio, 1.18; 95% confidence interval, 1.13-1.24; unemployment versus employment: odds ratio, 1.17; 95% confidence interval, 1.10-1.25). Among women, the corresponding associations were different (P<0.001 for sex-by-income quintile, sex-by-education level, and sex-by-labor market status interactions) and mainly nonsignificant. Results based on adherence trajectories showed that men in low SEP were likely to belong to trajectories presenting a fast decline in adherence. CONCLUSIONS: Low SEP was associated with overall and rapidly increasing statin nonadherence among men. Conversely, in women, associations between SEP and nonadherence were weak and inconsistent. Group-based trajectory modeling provided insight into the dynamics of statin adherence and its association with SEP.

Predictors of first-year statin medication discontinuation: A cohort study.

BACKGROUND: The discontinuation of statin medication is associated with an increased risk of cardiovascular and cerebrovascular events and, among high-risk patients, all-cause mortality, but the reasons for discontinuation among statin initiators in clinical practice are poorly understood. OBJECTIVE: To examine factors predicting the early discontinuation of statin therapy. METHODS: In this prospective cohort study, participants with baseline measurements before the initiation of statin treatment were linked to national registers and followed for the discontinuation of statins during the first year of treatment (no filled prescriptions after statin initiation within the subsequent 12 months). RESULTS: Of all the 9285 statin initiators, 12% (n = 1142) were discontinuers. Obesity, overweight, vascular comorbidities, and older age were independently associated with a reduced risk of discontinuation [odds ratios (OR) = 0.82 (95% confidence interval [CI], 0.69-0.99), 0.85 (95% CI, 0.73-0.98), 0.80 (95% CI, 0.68-0.93), and 0.82 (95% CI, 0.68-0.99), respectively]. In contrast, high-patient cost-sharing was associated with an increased odds (OR = 1.29; 95% CI, 1.03-1.62) for discontinuation. The only significant difference between the sexes (P = .002) was observed among the participants with risky alcohol use, which was associated with a decreased odds for discontinuation among the men (OR = 0.69; 95% CI, 0.49-0.98) and an increased odds among the women (OR = 1.28; 95% CI, 1.02-1.62). CONCLUSIONS: The discontinuation of statin therapy during the first year after initiation is common. Lowering out-of-pocket expenditures and focusing on low-risk patient groups and women with risky alcohol use could help maintain the continuation of medication.

Statin adherence and risk of acute cardiovascular events among women: a cohort study accounting for time-dependent confounding affected by previous adherence.

OBJECTIVES: Previous studies on the effect of statin adherence on cardiovascular events in the primary prevention of cardiovascular disease have adjusted for time-dependent confounding, but potentially introduced bias into their estimates as adherence and confounders were measured simultaneously. We aimed to evaluate the effect when accounting for time-dependent confounding affected by previous adherence as well as time sequence between factors. DESIGN: Retrospective cohort study. SETTING: Finnish healthcare registers. PARTICIPANTS: Women aged 45-64 years initiating statin use for primary prevention of cardiovascular disease in 2001-2004 (n=42 807). OUTCOMES: Acute cardiovascular event defined as a composite of acute coronary syndrome and acute ischaemic stroke was our primary outcome. Low-energy fractures were used as a negative control outcome to evaluate the healthy-adherer effect. RESULTS: During the 3-year follow-up, 474 women experienced the primary outcome event and 557 suffered a low-energy fracture. The causal HR estimated with marginal structural model for acute cardiovascular events for all the women who remained adherent (proportion of days covered ≥80%) to statin therapy during the previous adherence assessment year was 0.78 (95% CI: 0.65 to 0.94) when compared with everybody remaining non-adherent (proportion of days covered <80%). The result was robust against alternative model specifications. Statin adherers had a potentially reduced risk of experiencing low-energy fractures compared with non-adherers (HR 0.90, 95% CI 0.76 to 1.07). CONCLUSIONS: Our study, which took into account the time dependence of adherence and confounders, as well as temporal order between these factors, is support for the concept that adherence to statins in women in primary prevention decreases the risk of acute cardiovascular events by about one-fifth in comparison to non-adherence. However, part of the observed effect of statin adherence on acute cardiovascular events may be due to the healthy-adherer effect.

Natural history of bleeding and characteristics of early bleeders among warfarin initiators - a cohort study in Finland.

AIMS: The demand for oral anticoagulant therapy will continue to increase in the future along with the aging of the population. This study aimed to determine the rate of bleeding requiring hospitalization and to characterize early bleeders among persons initiating warfarin therapy. Characterization of those most susceptible to early bleeding is important in order to increase the safety of warfarin initiation. PATIENTS AND METHODS: Using data from nationwide health registers, we identified persons initiating warfarin therapy between January 1, 2009 and June 30, 2012, n=101,588, and followed them until hospitalization for bleeding, death, or administrative end of the study (December 31, 2012). We defined early bleeders as persons with a bleeding requiring hospitalization within 30 days since warfarin initiation. RESULTS: The rate of hospitalization for bleeding during a median follow-up of 1.9 years was 2.6% per person-year (95% confidence interval [CI] 2.5%-2.7%), with a peak within the first 30 days of warfarin initiation (6.5% per person-year, 95% CI 6.0%-7.1%). In a multivariable Cox proportional hazards regression analysis, early bleeders were characterized by prior bleeding (<180 days before initiation, hazard ratio [HR] =13.7, 95% CI 10.9-17.1; during 180 days-7 years before initiation, HR =1.48, 95% CI 1.15-1.90), male sex (HR =1.32, 95% CI 1.10-1.57), older age (HR =1.13, 95% CI 1.04-1.22, per 10-year increase), venous thrombosis (HR =1.83, 95% CI 1.44-2.34), pulmonary embolism (HR =1.46, 95% CI 1.11-1.91), alcohol abuse (HR =1.59, 95% CI 1.08-2.35), rheumatic disease (HR =1.40, 95% CI 1.07-1.83), and exposure to drugs with dynamic interaction mechanism with warfarin (HR =1.43, 95% CI 1.20-1.71). In age-adjusted models, Charlson comorbidity index and number of drugs predicted a graded increase in the hazard of early bleeding. CONCLUSION: The rate of hospitalizations for bleeding peaked in the beginning of warfarin therapy. Early bleeders were characterized by venous thrombosis, pulmonary embolism, and factors that increase bleeding risk without affecting the international normalized ratio.

Adherence to statin therapy and the incidence of ischemic stroke in patients with diabetes.

PURPOSE: We aimed to quantify for the first time the relationship between statin adherence and ischemic stroke (IS) in patients with diabetes. METHODS: Using Finnish health registers, we assembled a cohort of 52 868 statin initiators with diabetes in 1995-2006. We conducted a nested case-control analysis matching cases with IS with up to four controls for age, sex, date of statin initiation and follow-up duration. Adjusted rate ratios for IS were estimated with conditional logistic regression. Additional potential confounders were considered with inverse probability weighting and the role of unmeasured confounding using external adjustment. Statin adherence was measured as the proportion of days covered (PDC). RESULTS: Among 1703 cases and 6799 controls, good adherence to statins (PDC ≥ 80%) was associated with a 23% decreased incidence of IS (95%CI 14-32%) compared with poor adherence (PDC < 80%). This association remained broadly unchanged when stratified by sex, age, history of atherosclerotic cardiovascular disease or IS. There was a dose-response relationship between adherence level and the risk of IS (RR 0.63 [0.53-0.75] for PDC ≥ 80% versus PDC < 20%, P for trend <0.0001). Among patients with good adherence, those initiating with low intensity statin therapy had a 15% lower incidence (95%CI 2-27%) and those initiating with moderate intensity therapy a 29% lower incidence (16-41%) of IS compared with those with poor adherence who initiated with low intensity therapy. Our sensitivity analyses supported the robustness of the results. CONCLUSIONS: In diabetes, poor statin adherence may considerably increase the risk of IS both in primary and secondary prevention of IS.

Factors associated with nursing students' medication competence at the beginning and end of their education.

BACKGROUND: In previous studies, deficiencies in nursing students' medication competence have been highlighted. However, the focus of research has been limited especially to medication calculation competence and factors associated with it. In order to develop undergraduate nursing education and research, an understanding of the individual and learning environmental factors associated with medication competence from a broader approach is warranted. Our aim was therefore to evaluate the theoretical, practical and decision-making competence of nursing students and to identify factors associated with their medication competence at the beginning and end of their education. METHODS: We used a descriptive, correlational study design with a structured instrument including a set of potential associated factors, knowledge test, medication calculation test and patient vignettes. The participants were nursing students at the beginning (n = 328) and at the end of their education (n = 338). Data were analyzed statistically. RESULTS: In the evaluation of theoretical medication competence, the students' mean score over the semesters was 72 % correct answers in a knowledge test. In the evaluation of practical medication competence, the mean score was 74 % correct answers in a medication calculation test. In the evaluation of decision-making competence, the mean score was 57 % correct answers on deciding the best action in the situation given in patient vignettes. At the end of their education, students were able to solve patient vignettes significantly better. Individual factors were most evidently associated with medication competence. At the beginning of their education, students' previous academic success had a stronger association with medication competence. However, at the end of the education students' abilities in self-regulated learning and study motivation were more significant factors. CONCLUSION: The core elements of medication competence are significantly interrelated, highlighting the need to provide integrated and comprehensive medication education throughout the undergraduate education. Students' learning style is associated with medication competence. There is a need for methods to identify and support students having difficulties to self-regulate their learning. To increase the safety of medication care of patients, research focusing on the development of effective teaching methods is needed. This study produced information for future nursing education research in this field, especially for interventional studies.

Central Anticholinergic Adverse Effects and Their Measurement.

Drugs with anticholinergic properties are widely used. However, they may evoke a variety of adverse reactions (such as dry mouth and constipation, but also drowsiness and confusion), and therefore unnecessary use of drugs with anticholinergic properties should be avoided. In particular, older people are particularly vulnerable to the central anticholinergic effects of drugs. However, monitoring of drug-induced anticholinergic effects and drug concentrations in serum is challenging. In addition to the 'pure' anticholinergics such as atropine and oxybutynin, several other drugs whose principal mode of action is not anticholinergic, possess anticholinergic properties, thus increasing the risk of anticholinergic adverse effects. In this paper, we focus on the central anticholinergic effects of drugs, and on the usefulness of the serum anticholinergic assay (SAA) in the prediction of anticholinergic effects. Results on the anticholinergic effects of drugs on cognition are mixed. This may be because of differences in the populations as well as in the drugs used. In addition, the clinical conditions of the patients may affect the results. The SAA has been used in an attempt to measure anticholinergic burden. However, the results are variable and the SAA levels do not necessarily reflect the medication used by the patient. Therefore, its usefulness in determining anticholinergic adverse reactions is questionable.

Impact of Statin Adherence on Cardiovascular Morbidity and All-Cause Mortality in the Primary Prevention of Cardiovascular Disease: A Population-Based Cohort Study in Finland.

OBJECTIVES: To assess the extent to which adherence to statins is associated with the incidence of cardiovascular (CV) events and all-cause mortality in the primary prevention of CV diseases and whether different analytical approaches influence the observed associations. METHODS: This population-based cohort study used data from Finnish registers. The cohort included 97,575 new statin users aged 45 to 75 years in 2001 to 2004 with no CV diseases at baseline. Exposure was defined as adherence to statins (proportion of days covered [PDC]). The primary outcome was any CV event or death during a 3-year follow-up. Different analytical approaches, including multivariable-adjusted Cox regression, inverse probability weighting with time-varying adherence, and propensity score calibration, were used. RESULTS: During the first year of follow-up, 53% displayed good (PDC ≥80%), 26% had intermediate (PDC 40%-79%), and 21% exhibited poor (PDC <40%) adherence. After adjustment for sociodemographic and clinical covariates, a 25% relative risk reduction (hazard ratio [HR] 0.75; 95% confidence interval [CI] 0.71-0.79) was observed in the rate of any CV event or death among good versus poor adherers. Good adherers also had a lower incidence than poor adherers of acute coronary syndrome (HR 0.56; 95% CI 0.49-0.65) and acute cerebrovascular disease events (HR 0.67; 95% CI 0.60-0.76). The different analytical approaches achieved comparable results for all the outcomes. CONCLUSIONS: The incidence of CV events and mortality was higher in poor versus good adherers. Different analytical methods that took into account changes in adherence and confounding at baseline did not appreciably affect the results.

Analgesic use before and after oral anticoagulant initiation--a population-based study in Finland.

PURPOSE: Due to potential drug-drug interactions and subsequent bleeding risk, analgesic use should be reviewed when an oral anticoagulant is initiated. The aim of this study was to compare use of non-steroidal anti-inflammatory drugs (NSAIDs) and other analgesics before and after oral anticoagulant initiation. METHODS: All individuals who initiated warfarin, dabigatran, or rivaroxaban between January 2012 and September 2013 were identified from the Finnish Prescription Register. Prevalence of analgesic use during 3 months after oral anticoagulant initiation was compared to analgesic use during 4 months before initiation. Analgesics included were NSAIDs, paracetamol, paracetamol in doses ≥ 2 g/day, tramadol, and other opioids. Conditional logistic regression was used to calculate odds ratios (OR) with 95% confidence intervals (CI). RESULTS: In total, 54,025 initiated warfarin, 16,894 rivaroxaban, and 1569 dabigatran. The odds of NSAID use decreased among warfarin initiators (odds ratio (OR) 0.10; 95% confidence interval (CI) 0.09-0.10); 2.6% used NSAID after initiation. In contrast, the odds of NSAID use increased among rivaroxaban (OR 3.56; 95% CI 3.37-3.75) and dabigatran initiators (OR 1.44; 95% CI 1.16-1.78). The proportions using NSAIDs after the initiation were 69 and 32%, respectively. However, NSAID use decreased among dabigatran initiators with confirmed atrial fibrillation (OR 0.46; 95% CI 0.23-0.92) and among rivaroxaban initiators with a daily dose of ≥ 15 mg (OR 0.28; 95% CI 0.19-0.40). CONCLUSIONS: The use of NSAIDs decreases extensively among warfarin initiators which is encouraging. However, the use of NSAIDs increases among rivaroxaban and dabigatran initiators. This is a concern as the bleeding risk may increase due to potential pharmacodynamic interactions.

Accumulation of cardiovascular and diabetes medication among apparently healthy statin initiators.

PURPOSE: To characterize accumulation of drug-modifiable cardiovascular (CV) risk factors in statin initiators who had no prior medication or hospitalizations for CV disease or diabetes. METHODS: A cohort of 45-75-year-old statin initiators in Finland with no prior CV diseases, diabetes or medication for these conditions was followed up for 24 months after statin initiation for accumulation of CV and diabetes drugs. The number of drugs was measured semi-annually since the first statin purchase and analyzed by growth mixture modeling. RESULTS: Of the 11 948 apparently healthy statin initiators, 34% purchased at least one additional CV or diabetes drug during the subsequent 24 months. Of those, 20% redeemed no other CV or diabetes drugs at statin initiation but started to accumulate them after 18 months of follow-up, receiving on average 1.3 other drugs at 24 months. The majority, 59%, redeemed on average 0.5 drugs at statin initiation and accumulated 1.5 drugs by the end of 24-month follow-up. Seventeen percent received 1 additional drug at statin initiation, accumulating on average 3 drugs. The remaining 4% with an average of 2 CV or diabetes drugs at statin initiation redeemed 3.5 additional drugs during the follow-up. CONCLUSIONS: Two years after statin initiation, 2 in 3 apparently healthy initiators could still be defined as such as reflected by CV and diabetes medication use.