Trend of Antihypertensive Medicine Use in the Baltic States between 2008 and 2018: A Retrospective Cross-National Comparison

High blood pressure is a major risk factor contributing to death and disability rates in the Baltic states. The aim of this study was to compare the utilization of antihypertensive medicines in Estonia, Latvia and Lithuania from 2008 to 2018. In this retrospective cross-national comparison, nationally representative wholesale data from the IQVIA National Retail Audit were analyzed. The utilization of inhibitors of the renin–angiotensin system, beta blockers, calcium channel blockers, diuretics and centrally acting antihypertensives by Defined Daily Doses per 1000 inhabitants and day (DDD/TID) was used to calculate utilization. Time series analysis was used to analyze trends. The utilization increased annually by 10.88, 8.04 and 6.42 DDD/TID in Estonia, Latvia and Lithuania, respectively, from 2008. The utilization of antihypertensive drugs in 2018 was 372, 267 and 379.5 DDD/TID, respectively. Inhibitors of the renin–angiotensin system were the most commonly used class in 2008 and 2018. From 2008, the utilization of beta blockers and fixed-dose combinations including renin–angiotensin system inhibitors increased substantially, while that of calcium channel blockers decreased. Country-specific utilization trends were noted; e.g., the utilization of centrally acting antihypertensives was 30.9 DDD/TID in Lithuania compared to 3.01 DDD/TID in Estonia and 16.17 DDD/TID in Latvia. The use of antihypertensive medicines increased over the study period, but the trends for the different drug classes differed between countries

Differences in utilisation rates between commercial and administrative databases : implications for future health economic and cross national studies

Comparative cross national (CNC) drug utilization studies are challenging. However, there can be concerns with the accuracy and robustness of the data collected with previous studies showing differences in utilisation rates between different databases. In addition, if utilisation rates vary appreciably between countries with no logical explanation. These studies have been carried out for the same class across countries. This has now been extended to compare utilisation rates between different databases among four high volume classes among administrative and commercial databases in one country (Lithuania) between 2004 and 2012 alongside health policies. There were appreciable differences in the utilisation of PPIs (5 to 7 fold) and statins (2 to 6 fold) between the different databases with limited differences for the other two classes. This could be explained by restricted reimbursement for the PPIs and statins, with similar utilisation of renin-angiotensin inhibitors in Lithuania between the databases and with Western European countries in the absence of prescribing restrictions. Low utilisation of anti-depressants in Lithuania versus Western European countries also explained by ongoing policies. Essential to always record the database content in CNC studies alongside health policies otherwise the findings could be misinterpreted. Joint reporting should become standard for future CNC studies

Non-persistence to antihypertensive drug therapy in Lithuania

Purpose: Poor persistence to antihypertensive therapy is an important cause of treatment failure. Investigating persistence is especially important in countries with a high cardiovascular mortality, like Lithuania. The aim of this study was to describe the antihypertensive treatment at initiation, to determine the percentage of patients not being persistent with antihypertensive treatment after 1 year and to explore factors associated with non-persistence. Methods: In this cohort study, data on dispensed prescription medicines from the Lithuanian National Health Insurance Fund (NHIF) were used. All adult patients with a diagnosis of hypertension having first antihypertensive dispensed in 2018 were included. Descriptive statistics was used to determine the number of patients started with monotherapy and combination therapy. Treatment choice by Anatomical Therapeutic Chemical (ATC) and number of active pharmaceutical ingredient (API) was described. Non-persistence was assessed using the anniversary method. Multivariate logistic regression was used to explore factors associated with non-persistence. Results: A total of 72,088 patients were included into the study, 56% started on monotherapy treatment, with 49% being dispensed an angiotensin converting enzyme inhibitor, and 44% started on combination therapy. Overall, 57% of patients were non-persistent after 1 year. Patients’ gender and prescriber qualification showed no association with non-persistence. Younger patients, patients from rural area, patients started with monotherapy, and patients with no medication change had higher odds to become non-persistent. Conclusions: The majority of patients were initiated with treatment following hypertension management guidelines, but it is of concern that over half of the patients were non-persistent to antihypertensive therapy in the first year

Use of Generics—A Critical Cost Containment Measure for All Healthcare Professionals in Europe?

Pharmaceutical expenditures in ambulatory care rose rapidly in Europe in the 1990s and early 2000s. This was typically faster than other components of healthcare spending, leading to reforms to moderate future growth. A number of these centered on generic medicines with measures to lower reimbursed prices as well as enhance their prescribing and dispensing. The principal objective of this paper is to review additional measures that some European countries can adopt to further reduce reimbursed prices for generics. Secondly, potential approaches to address concerns with generics when they arise to maximize savings. Measures to enhance the prescribing of generics will also briefly be discussed. A narrative review of the extensive number of publications and associated references from the co-authors was conducted supplemented with known internal or web-based articles. In addition, health authority and health insurance databases, principally from 2001 to 2007, were analyzed to assess the impact of the various measures on price reductions for generic omeprazole and generic simvastatin vs. pre-patent loss prices, as well as overall efficiency in Proton Pump Inhibitor (PPI) and statin prescribing. The various initiatives generally resulted in considerable lowering of the prices of generics as well as specifically for generic omeprazole and generic simvastatin vs. pre-patent loss prices. At one stage in the UK, generic simvastatin was just 2% of the originator price. These measures also led to increased efficiency for PPI and statin prescribing with reimbursed expenditure for the PPIs and statins either falling or increasing at appreciably lower rates than increases in utilization. A number of strategies have also been introduced to address patient and physician concerns with generics to maximize savings. In conclusion, whilst recent reforms have been successful, European countries must continue learning from each other to fund increased volumes and new innovative drugs as resource pressures grow. Policies regarding generics and their subsequent impact on reimbursement and utilization of single sourced products will continue to play a key role to release valuable resources. However, there must continue to be strategies to address concerns with generics when they exist

Policies to Enhance Prescribing Efficiency in Europe: Findings and Future Implications

Introduction: European countries need to learn from each other to address unsustainable increases in pharmaceutical expenditures. Objective: To assess the influence of the many supply and demand-side initiatives introduced across Europe to enhance prescribing efficiency in ambulatory care. As a result provide future guidance to countries. Methods: Cross national retrospective observational study of utilization (DDDs – defined daily doses) and expenditure (Euros and local currency) of proton pump inhibitors (PPIs) and statins among 19 European countries and regions principally from 2001 to 2007. Demand-side measures categorized under the “4Es” – education engineering, economics, and enforcement. Results: Instigating supply side initiatives to lower the price of generics combined with demand-side measures to enhance their prescribing is important to maximize prescribing efficiency. Just addressing one component will limit potential efficiency gains. The influence of demand-side reforms appears additive, with multiple initiatives typically having a greater influence on increasing prescribing efficiency than single measures apart from potentially “enforcement.” There are also appreciable differences in expenditure (€/1000 inhabitants/year) between countries. Countries that have not introduced multiple demand side measures to counteract commercial pressures to enhance the prescribing of generics have seen considerably higher expenditures than those that have instigated a range of measures. Conclusions: There are considerable opportunities for European countries to enhance their prescribing efficiency, with countries already learning from each other. The 4E methodology allows European countries to concisely capture the range of current demand-side measures and plan for the future knowing that initiatives can be additive to further enhance their prescribing efficiency

Development of Risk Prediction Equations for Incident Chronic Kidney Disease

IMPORTANCE ‐ Early identification of individuals at elevated risk of developing chronic kidney disease  could improve clinical care through enhanced surveillance and better management of underlying health  conditions.  OBJECTIVE – To develop assessment tools to identify individuals at increased risk of chronic kidney  disease, defined by reduced estimated glomerular filtration rate (eGFR).  DESIGN, SETTING, AND PARTICIPANTS – Individual level data analysis of 34 multinational cohorts from  the CKD Prognosis Consortium including 5,222,711 individuals from 28 countries. Data were collected  from April, 1970 through January, 2017. A two‐stage analysis was performed, with each study first  analyzed individually and summarized overall using a weighted average. Since clinical variables were  often differentially available by diabetes status, models were developed separately within participants  with diabetes and without diabetes. Discrimination and calibration were also tested in 9 external  cohorts (N=2,253,540). EXPOSURE Demographic and clinical factors.  MAIN OUTCOMES AND MEASURES – Incident eGFR <60 ml/min/1.73 m2.  RESULTS – In 4,441,084 participants without diabetes (mean age, 54 years, 38% female), there were  660,856 incident cases of reduced eGFR during a mean follow‐up of 4.2 years. In 781,627 participants  with diabetes (mean age, 62 years, 13% female), there were 313,646 incident cases during a mean follow‐up of 3.9 years. Equations for the 5‐year risk of reduced eGFR included age, sex, ethnicity, eGFR, history of cardiovascular disease, ever smoker, hypertension, BMI, and albuminuria. For participants  with diabetes, the models also included diabetes medications, hemoglobin A1c, and the interaction  between the two. The risk equations had a median C statistic for the 5‐year predicted probability of  0.845 (25th – 75th percentile, 0.789‐0.890) in the cohorts without diabetes and 0.801 (25th – 75th percentile, 0.750‐0.819) in the cohorts with diabetes. Calibration analysis showed that 9 out of 13 (69%) study populations had a slope of observed to predicted risk between 0.80 and 1.25. Discrimination was  similar in 18 study populations in 9 external validation cohorts; calibration showed that 16 out of 18 (89%) had a slope of observed to predicted risk between 0.80 and 1.25. CONCLUSIONS AND RELEVANCE – Equations for predicting risk of incident chronic kidney disease developed in over 5 million people from 34 multinational cohorts demonstrated high discrimination and  variable calibration in diverse populations

Corrigendum to "Utilisation trend of long-acting insulin analogues including biosimilars across Europe: findings and implications"

In the article titled "Utilisation Trend of Long-Acting Insulin Analogues including Biosimilars across Europe: Findings and Implications" [1], the captions of Figures 3 and 4 were incorrect. The corrected captions for Figures 3 and 4 appear below

Discontinuation of antidepressants in suicides findings from the Friuli Venezia Giulia Region, Italy, 2005-2014

6siAlthough 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)partially_openembargoed_20200331Castelpietra, Giulio; Bortolussi, Luca; Gobbato, Michele; Arnoldo, Luca; Balestrieri, Matteo; Wettermark, BjornCastelpietra, Giulio; Bortolussi, Luca; Gobbato, Michele; Arnoldo, Luca; Balestrieri, Matteo; Wettermark, Bjor