Joëlle A. Erkens

Drug Treatment of Benign Prostatic Hyperplasia and Hospital Admission for BPH-Related Surgery

OBJECTIVE To investigate whether there is a difference in the risk of progressing to BPH-related prostatic surgery between patients using alpha-blockers and patients using the 5-alpha-reductase inhibitors (5-ARIs). METHODS A population-based cohort study was conducted, using data from the PHARMO Record Linkage System. We identified 5671 patients (> or =50 years old, no history of using both alpha-blockers and 5-ARIs, more than one year of database history prior to the first date of BPH drug-dispensing), who filled at least one prescription for either alpha-blockers (alfuzosin, tamsulosin, terazosin) or 5-ARIs (finasteride). The incidence of BPH-related surgery was compared between patients treated with alpha-blockers and patients treated with 5-ARIs. RESULTS The cumulative incidence of BPH-related prostatic surgery was 15.2% and mainly involved transurethral resection of the prostate (TURP) (13.4%). Patients using alpha-blockers had a significantly increased risk of BPH-related prostatic surgery compared to patients using 5-ARIs, which remained after adjusting for age, calendar time, type of prescriber and chronic disease score (adjusted HR: 1.52, 95% CI: 1.24-1.88). The difference between alpha-blockers and 5-ARIs was sustained after stratification of time period (<1995, > or =1995) and exclusion of patients with prostatic surgery within one month of treatment initiation. CONCLUSIONS It is concluded that alpha-blocker treated patients had a higher risk of BPH-related surgery compared to 5-ARI treated patients. Additional research on the long-term outcomes and risk factors for the natural progression of BPH is necessary to identify the optimal medical treatment for BPH patients according to their baseline characteristics.

Determinants of non-compliance with bisphosphonates in women with postmenopausal osteoporosis

ABSTRACT Objective: To identify determinants of non-compliance with bisphosphonates in women with postmenopausal osteoporosis. By considering the year of the introduction of weekly bisphosphonates important additional information is obtained. Methods: New female users of daily or weekly alendronate or risedronate between 1999 and 2004, aged ≥ 45 years were identified from PHARMO RLS, including drug-dispensing and hospitalisation data of > 2 million residents of the Netherlands. One-year compliance with bisphosphonates was measured using the Medication Possession Ratio (MPR). To identify determinants of non-compliance, non-compliant women (MPR < 50%) were compared to compliant women (MPR ≥ 80%). The effect of patient age, prescriber, initial dosing regimen, gastrointestinal adverse events, co-medication and fractures on non-compliance was investigated. Results: The study cohort included 8822 new users of bisphosphonates, of whom 5079 (58%) were compliant and 2720 (31%) were non-compliant after 1 year. Only 1023 women (11%) had a MPR between ≥ 50% and < 80%. Daily dosing at start, increased number of co-medications and new use of intestinal agents in the year after starting bisphosphonates were independently associated with an increased odds of non-compliance. In contrast, higher age, first prescription from a specialist, osteoporosis related hospitalisation and use of NSAIDs in the year preceding bisphosphonate therapy decreased the odds of non-compliance. Conclusion: This study revealed several determinants of non-compliance with bisphosphonates, the best controllable being the type of initial bisphosphonate, with daily dosing leading to more non-compliance than weekly dosing. However, compliance for both regimens is suboptimal, pointing to an unmet medical need.

Treatment with inhaled corticosteroids in asthma is too often discontinued

To study persistence with inhaled corticosteroids (ICS) and its determinants in asthma‐patients.

Extent of uncontrolled disease and associated medical costs in severe asthma--a PHARMO study.

ABSTRACT Objective: Asthma is a major public health problem with considerable economic impact. The highest costs being observed in patients with severe asthma. Furthermore, despite the use of recommended therapies, asthma control can still be poor. Therefore, the objective of this study was to assess the extent of uncontrolled disease and associated medical costs in severe asthma. Methods: The PHARMO Record Linkage System includes among others drug dispensing and hospitalizations for ≥ 2 million subjects in The Netherlands. Severe asthma patients used long-acting beta-agonists and inhaled corticosteroids for over 200 days and short-acting beta-agonists for at least 100 days in 2004. Severe uncontrolled asthma was defined as a hospitalization for asthma or use of multiple short courses of oral corticosteroids assessed in 2004. Reimbursed costs of asthma drugs and hospitalizations were calculated during this year. A matched nested-case control study was performed to identify treatment-related risk factors for uncontrolled disease. Information on clinical diagnosis of (severity of) asthma was not available. Results: About 17% of patients with severe asthma aged 12–49 years (N = 1158) showed lack of control. Excess drug costs for severe uncontrolled asthma with hospitalization mounted up to 700 Euro per patient per year and 300 Euro per patient per year for patients without hospitalization. Including hospital admission costs, excess costs mounted up to over 10 000 Euro per patient per year. Lack of control did not seem to be caused by under-treatment. Conclusion: Poor control of severe asthma leads to disproportionately increased direct costs compared to severe controlled asthma, especially when hospital admission is required.

Effect of non-persistent use of oral glucose-lowering drugs on HbA1c goal attainment

ABSTRACT Objectives: The aim of this study was to quantify the effect of non-persistence with oral glucose-lowering drugs (OGLD) on HbA1c goal attainment (< 7%) in daily practice. Methods: From the PHARMO Record Linkage System comprising among others linked drug dispensing and clinical laboratory data from approximately 2.5 million individuals in the Netherlands, new users of OGLD in the period 1999–2004 were identified. Patients with a baseline HbA1c ≥ 7% and at least one HbA1c measurement in the period of 6–12 months after treatment onset were included in the study cohort. Persistence with OGLD in the first year of treatment was determined using the method of Catalan. In case the first treatment episode overlapped the first HbA1c measurement within 6–12 months after treatment onset, a patient was considered persistent at that measurement. Patients with a HbA1c < 7% were defined as having attained goal. Results: The study cohort included 2023 patients with a mean baseline HbA1c of 8.9 ± 1.8%. Three-quarters (1512 patients) were persistent with any OGLD at the first HbA1c measurement within 6–12 months after treatment onset; of these, 861 (57%) were at goal. Of the 511 non-persistent patients, 239 (47%) were at goal. Non-persistent patients were about 20% less likely to attain goal (RRadj 0.82; 95%CI 0.74–0.91), compared to persistent OGLD users. Conclusion: Non-persistent use of OGLD leads to a 20% decreased probability of HbA1c goal attainment in daily practice. This effect of non-persistence seems modest, but represents around 12 000 new and 10 000 prevalent OGLD users a year in the Netherlands in whom OGLD use could be better controlled.

Cardiovascular risk factors and diseases precede oral hypoglycaemic therapy in patients with type 2 diabetes mellitus

Although patients with type 2 diabetes mellitus and cardiovascular disease share common risk factors, the link between these diseases remains largely unexplained. In this case-control study, the earlier use of cardiovascular drugs (before the diagnosis of diabetes) was investigated among cases with type 2 diabetes mellitus and controls without diabetes. Using the PHARMO database, we identified 4,864 patients who were prescribed oral hypoglycaemic agent (OHA) therapy between 1985-1998 in the Netherlands. For each case, two controls matched on age, sex and pharmacy were randomly selected. Controls had not received insulins or OHA therapy. There were 2,656 (55.0%) cases compared with 2,727 (28.1%) controls who used cardiovascular drugs at the start of OHA therapy. Cases had a 3.5-fold increased risk of cardiovascular drug use (OR(95% CI) = 3.5 [3.2-3.8]) compared to controls. Differences in cardiovascular drug use were noted as early as 7 years before the start of OHA therapy, distinguishing cases from controls. Our finding that patients with type 2 diabetes mellitus were more likely to receive treatment for cardiovascular disease several years before they start diabetes therapy supports the hypothesis of a common underlying mechanism of these two disorders and stresses the importance of the pre-diabetic state.

Initiation of glucose-lowering therapy in Type 2 diabetes mellitus patients in general practice

Aim  The purpose of this study was to investigate which factors determine the initiation of glucose‐lowering therapy in patients with Type 2 diabetes mellitus in general practice and their future glycaemic control.

PCV5 NON-PERSISTENT USE OF ANTIHYPERTENSIVE DRUGS INCREASES RISK OF HOSPITALIZATIONS FOR STROKE BY NEARLY 20%

PCV5 NON-PERSISTENT USE OF ANTIHYPERTENSIVE DRUGS INCREASES RISK OF HOSPITALIZATIONS FOR STROKE BY NEARLY 20% Breekveldt-Postma NS, Siiskonen SJ, Penning-van Beest FJA, Erkens JA,Vincze G, Falvey H, Herings RMC PHARMO Institute, Utrecht,The Netherlands, Novartis Pharma AG, Basel, Switzerland OBJECTIVES: Low persistence with antihypertensive drug treatment (AHT) is expected to limit patient’s benefits in terms of a reduction of cardiovascular and cerebrovascular disease. This study investigated the relationship between persistence with antihypertensive drugs and the risk of stroke in clinical practice. METHODS: From the PHARMO Record Linkage System comprising, among others, linked drug-dispensing and hospital records of >2 million inhabitants in The Netherlands, new users of AHT were identified in the period 1993–2002. Persistence with AHT was determined by summing the number of days of continuous treatment (gaps between dispensings of <60 days). Patients were classified as persistent if they remained on AHT for at least two years. The outcome of interest was the first hospital admission for stroke occurring two or more years after initiation of AHT therapy. Patients were classified as high, intermediate or low cardiovascular risk based on other cardiovascular drug use and hospitalizations during the first two years of follow-up. RESULTS: The study included 98,485 patients of whom 16% were at high cardiovascular risk. About 50% (n = 48,548) of all patients were persistent with AHT for two years, and 2.1% (n = 2093) were hospitalized for stroke in the period of two or more years after initiation of AHT therapy. Multivariate analyses showed that non-persistent users of AHT had a 16%–19% increased risk for stroke compared to persistent users (Low/intermediate risk group RRadj = 1.19; 95% CI: 1.07–1.32; high risk group RRadj = 1.16; 95% CI: 0.97–1.39). CONCLUSION: In clinical practice antihypertensive drug treatment is used over too short a time interval to have maximum benefit from preventing stroke.

PDB69 DETERMINANTS OF STOPPING TREATMENT WITH ORAL ANTIDIABETIC DRUGS IN DAILY CLINICAL PRACTICE

DETERMINANTS OF STOPPINGTREATMENTWITH ORAL ANTIDIABETIC DRUGS IN DAILY CLINICAL PRACTICE Koerselman J, van der Bij S, Erkens JA, Kessabi S, Groot MT, Penning-van Beest FJA, Herings RMC PHARMO Institute, Utrecht, Utrecht,The Netherlands, Novartis Pharma AG, Basel, Switzerland, Novartis Pharma B.V, Arnhem,The Netherlands OBJECTIVES: In daily practice many Type 2 Diabetes Mellitus (T2DM-)patients discontinue treatment. Therefore, the aim of this study was to investigate the determinants of (non-) persistence with oral antidiabetic drugs (OADs) in daily clinical practice. METHODS: From the PHARMO record linkage system, comprising among others linked drug-dispensing, and hospital data for >2.3 million subjects in The Netherlands, new users of OADs were identified in the period 1999–2005. Patients with 1 year of follow-up, were included in the study-cohort. Persistence with OAD-treatment in the first year of therapy was determined using the method of Catalan. Potential determinants of (non-)persistence included patient-characteristics, type of initial OAD-therapy, and cardiovascular co-morbidity. RESULTS: The study included 33,299 new users of OADs. One year after start, 42% of new T2DM-patients had stopped using any OAD. The risk of non-persistence was decreased with male gender (HR: 0.97; 95% CI: 0.94–1.00), and cardiovascular drug use (HR: 0.91; 95% CI: 0.86–0.97). Regarding age, compared to patients 76 years, the age-group 55–75 years had a 16% lower risk, and the age-group 30–44 years had a 32% increased risk of non-persistence. Patients starting on combined metformin + SU had a lower risk of non-persistence with any OAD; compared to patients starting on metformin monotherapy, the risk was 23% lower (HR: 0.77; 95% CI: 0.70–0.85). The risk of nonpersistence was increased with a specialist as first prescriber (HR: 1.20; 95% CI: 1.15–1.26), higher initial daily dose (HR: 1.09; 95% CI: 1.00–1.22), and higher initial daily dosing frequency (HR: 1.10; 95% CI: 1.02–1.20). CONCLUSION: In daily clinical practice about 40% of new T2DM-patients stop OADtherapy within one year. Determinants of stopping OADmedication were male gender, age-group, specialist as first prescriber, dosing, cardiovascular drug-use, and type of initial OAD-treatment.