Leena K. Saastamoinen

Long-Term Persistence with Statin Therapy: A Nationwide Register Study in Finland

BACKGROUND Preventive statin therapy is often recommended as lifelong treatment. OBJECTIVE The aim of this study was to analyze persistence with statin therapy over a decade of use and to identify factors associated with its discontinuation. METHODS Persistence with therapy among new users of statins in 1995 was followed up until December 31, 2005, in Finland using the nationwide drug reimbursement register. Cumulative persistence was analyzed using Kaplan-Meier analysis. A Cox regression model was applied to analyze associations of various baseline covariates with discontinuation. We further modeled the association of time-specific covariates by stratifying the duration of therapy in years and using a logistic regression in which those continuing therapy until the end of follow-up (persistent users) formed the reference group. Adherence, defined as the proportion of days covered by statins, stratified by the timing of discontinuation, was computed for the respective groups. RESULTS Of the 18,072 new statin users, 73.3% (n =13,254) were aged >54 years and 54.8% (n =9908) were men. Of this cohort, 43.9% (n = 7926) were using statins throughout and at the end of the tenth year. Sex was not associated with persistence at any point. In the Cox model, persons aged 45 to 74 years at initiation were more likely to continue statin use than younger or older age groups. Among those who still used statins after the fifth year of observation, the age difference was not observed in the logistic regression model. The use of 1, 2, 3, or > or =4 cardiovascular drugs before the initiation predicted continuation relative to no cardiovascular drug use (hazard ratio for discontinuation significantly <1.00 in all comparisons). Adherence was best (median 93.9%) among the persistent users. CONCLUSIONS The 10-year persistence with statin use in this general population was approximately 44%. Persons aged 45 to 74 years at initiation and those with at least 1 prescription for another cardiovascular medication were the most likely to continue statin therapy up to the fifth year.

Impact of restricted reimbursement on the use of statins in Finland: a register-based study.

Objectives:New and expensive medicines are a driving force behind growth in medicine costs, and policies promoting use of less expensive products have been widely introduced. This study investigated the short-term consequences of the restricted reimbursement of expensive statins (atorvastatin and rosuvastatin) on the use of statins in Finland. Methods:Data on patients purchasing atorvastatin, rosuvastatin, or simvastatin in 2002–2007 were retrieved from the nationwide Prescription Register. Outcome measures included the time trend in the numbers of purchasers and initiators of different statins, the morbidities of new users before and after the new policy, and the proportion of users of expensive statins switching to other statins. Results:After the restriction, the numbers of purchasers of atorvastatin and rosuvastatin dropped, and atorvastatin and rosuvastatin were seldom prescribed as first-line therapy. Before the restriction, 20.9% of new users of atorvastatin and 18.4% of those of rosuvastatin had either coronary artery disease or familial hyperlipidemia. After the restriction the corresponding figures were 28.7% and 26.8%. After the restriction new users of atorvastatin and rosuvastatin were also more likely to use other cardiovascular medicines or antidiabetics or to have previous statin purchases. A total of 57.6% of those using atorvastatin and 49.2% of those using rosuvastatin before the restriction switched to a less expensive statin. Conclusions:Restricted reimbursement of expensive statins decreased their use. It seems that after the policy new statin treatments have channeled appropriately. Although it is likely that the cost-containment aim of the policy was reached, health and long-term effects are not known.

International trends in clozapine use: a study in 17 countries

There is some evidence that clozapine is significantly underutilised. Also, clozapine use is thought to vary by country, but so far no international study has assessed trends in clozapine prescribing. Therefore, this study aimed to assess clozapine use trends on an international scale, using standardised criteria for data analysis.

Measurement of statin exposure in the absence of information on prescribed doses

Letter to the editor Pharmacoepidemiological studies on statin use and effectiveness frequently use pharmacy-claims databases as a source of drug exposure data. A variety of methods have been developed to estimate adherence and persistence based on pharmacy-claims databases [1–3]. In each method, theoretical duration of prescriptions is estimated by dividing the quantity dispensed by the prescribed dose. However, many pharmacyclaims databases, including all databases in the Nordic countries, do not include information on days’ supply or prescribed doses in a structured format [4]. Therefore, theoretical duration of statin prescriptions is often estimated based on assumed doses, such as one unit per day [5, 6] or a dose equal to defined daily dose (DDD) per day [7]. In this study, we evaluated the validity of the dosage assumptions of one unit per day and DDD per day for estimating the theoretical duration of statin prescriptions. We identified all statin prescriptions (Anatomical Therapeutic Chemical classification code C10AA [8]) dispensed in May 2007 from the Finnish Prescription Register. We converted free-text dosing instructions into numerical form and analyzed the proportions of prescriptions in which the prescribed daily dose deviated from one unit and DDD, using DDDs available in 2014 [8]. In addition, we described the distribution of prescribed daily doses of statins with means, standard deviations, medians and interquartile ranges. Of all statin prescriptions (n=153,664), 4.2 % were prescribed with a dose other than one unit per day (Table 1). The proportion varied from 0.7 to 12.9 % across individual statins. In contrast, 90.5% of statin prescriptions were prescribed with a dose other than DDD per day. Among individual statins, the proportion varied from 21.8 to 100 %, being 99.2 % for simvastatin. The proportion was similar (99.9 % of simvastatin prescriptions) if the former version of the DDD (15mg) was applied. Our study indicated that the duration of statin prescriptions can be validly estimated by assuming a daily dose of one unit. Our finding is in accordance with two previous studies showing that at least ∼95 % of statin prescriptions are prescribed with a daily dose of one unit [9, 10]. Furthermore, we showed that only one in ten statin prescriptions may be prescribed with a dose equal to DDD per day, indicating that assumed dose of DDD per day would most likely either overor underestimate the duration of statin prescriptions. This would lead to misclassifications of adherence and persistence levels and consequently biased measures of association when studying health outcomes associated with adherence to and discontinuation of statin therapy. Despite the fact that prescribed doses of statins have shown some differences between European countries [11] and seem to have increased over time [11–13], we believe that our finding about lack of validity of the dosage assumption of DDD per day is generalizable to other countries and time periods because statins are unlikely to be prescribed with a dose equal to DDD only. In addition, for statins other than atorvastatin and rosuvastatin, DDD is an average of two T. Romppainen : E. Aarnio School of Pharmacy, University of Eastern Finland, Kuopio, Finland

An intervention to develop repeat prescribing in community pharmacy

Background:  Lack of review of patients’ medications in repeat prescribing is common. This and other problems in repeat prescribing need to be addressed. Community pharmacists could be more proactive in the review of chronic medications.

Impact of Regulatory Safety Warnings on the Use of Antidepressants among Children and Adolescents in Finland

OBJECTIVE The aim of this study was to analyze changes in the prevalence and incidence of antidepressant use among children and adolescents in Finland post October, 2003. METHOD The sample comprised all children and adolescents in Finland aged < or =19.0 years (n = 27,676) who collected one or more reimbursed prescriptions for an antidepressant in noninstitutional and nonhospital settings between January, 1998, and December, 2005. Time-series models were used to compare antidepressant use 60 months before and 24 months after the health advisory issued by the Food and Drug Administration (FDA) in October, 2003. RESULTS The annual prevalence (users/1,000 youths) of antidepressant use increased from 5.24 in 2002 to 5.93 in 2005. There was an increase in the monthly incidence (users = 1,000 youths) of selective serotonin reuptake inhibitors (SSRIs) use (+0.02498), fluoxetine use (+0.00691), and sertraline use (+0.00727) post October, 2003. When considering preadvisory trends in antidepressant use, only fluoxetine use was higher than the predicted post October 2003, use (<0.001). The use of all other SSRIs was significantly lower than predicted. CONCLUSIONS In contrast to many other countries, the use of antidepressants continued to increase among children and adolescents in Finland post October, 2003. While the rate of fluoxetine use increased, there was a decline in the rate at which all other SSRIs were used.

Repeat prescribing in primary care: a prescription study

Objective There is limited knowledge on repeat prescribing of different drug groups in cases where the physician does not see the patient. This study aimed to investigate the frequency of repeat prescribing of different drug groups both with and without consultation. Method The study was a nationwide prescription database study performed in Finnish primary care in 2001. Each physician in a sample of 400 physicians was asked to report all patient contacts over a specified period of five consecutive working days once over a period of six months, and another sample of 400 physicians did the same for the next six months. Copies of physicians’ prescriptions were collected and data on the drugs and type of prescriptions were recorded. Repeat prescriptions issued with and without a consultation were included. ResultsAbout 19% of all prescriptions were issued without direct contact between the physician and the patient. In the different drug groups, the range was from 2% of antibiotics to 57% of antipsychotics. Psychotropics including hypnotics and tranquillizers, cardiovascular drugs and drugs for elderly patients were most often issued without consultation. Conclusion Repeat prescribing without consultation is common especially for elderly patients and users of psychotropics and cardiovascular drugs, and this may contribute to suboptimal therapy.

International trends in antipsychotic use : A study in 16 countries, 2005-2014

The objective of this study was to assess international trends in antipsychotic use, using a standardised methodology. A repeated cross-sectional design was applied to data extracts from the years 2005 to 2014 from 16 countries worldwide. During the study period, the overall prevalence of antipsychotic use increased in 10 of the 16 studied countries. In 2014, the overall prevalence of antipsychotic use was highest in Taiwan (78.2/1000 persons), and lowest in Colombia (3.2/1000). In children and adolescents (0-19 years), antipsychotic use ranged from 0.5/1000 (Lithuania) to 30.8/1000 (Taiwan). In adults (20-64 years), the range was 2.8/1000 (Colombia) to 78.9/1000 (publicly insured US population), and in older adults (65+ years), antipsychotic use ranged from 19.0/1000 (Colombia) to 149.0/1000 (Taiwan). Atypical antipsychotic use increased in all populations (range of atypical/typical ratio: 0.7 (Taiwan) to 6.1 (New Zealand, Australia)). Quetiapine, risperidone, and olanzapine were most frequently prescribed. Prevalence and patterns of antipsychotic use varied markedly between countries. In the majority of populations, antipsychotic utilisation and especially the use of atypical antipsychotics increased over time. The high rates of antipsychotic prescriptions in older adults and in youths in some countries merit further investigation and systematic pharmacoepidemiologic monitoring.

Register-based indicators for potentially inappropriate medication in high-cost patients with excessive polypharmacy†

Excessive polypharmacy is often associated with inappropriate drug use. Because drug expenditures are heavily skewed and a considerable share of patients in the top 5% of the cost distribution have excessive polypharmacy, the appropriateness of their drug use should be reviewed.

Measuring psychotropic drug exposures in register-based studies – validity of a dosage assumption of one unit per day in older Finns

Pharmacoepidemiological studies provide valuable information on the relationships between psychotropic drug use and adverse outcomes in older people. To minimize the influence of misclassification bias in pharmacoepidemiological studies, more emphasis should be given to methodological aspects of exposure assessment. This study evaluated the validity of a dosage assumption of one unit per day for measuring legend duration of psychotropic drug exposures among older people. Using data from the Finnish Prescription Register, the study analysed 62,320 psychotropic drug prescriptions dispensed for people aged ≥ 75 years (n = 52,729) in September 2009. The proportions of prescriptions in which the prescribed dose deviated from one unit per day were assessed for categories and subcategories of psychotropic drugs. The prescription was considered misclassified (a) if the prescribed drug was intended for “as needed” use, (b) if the prescription included a dose range, or (c) if the prescribed dose was below or above one unit per day. Among antidepressants, less than every fourth (23.7%) prescription was misclassified. The proportions of misclassification varied substantially across subcategories, being 13.1% for selective serotonin reuptake inhibitors (SSRIs), 25.3% for other antidepressants and 53.8% for tricyclic antidepressants. Of the benzodiazepine and antipsychotic prescriptions, 79.9% and 57.6%, respectively, were misclassified. In conclusion, the dosage assumption of one unit per day is valid for measuring the legend duration of SSRI and other antidepressant exposures among older people. Among other psychotropic drugs, the dosage assumption is likely to lead to severe exposure misclassification. Copyright