Effect of persistent use of antihypertensives on blood pressure goal attainment.

OBJECTIVE: Discontinuation rates with antihypertensive drugs in real life are high. The present study investigates the relationship between persistence with antihypertensive drugs (AHT) and blood pressure (BP) goal attainment in daily clinical practice. METHODS: In the PHARMO Record Linkage System, which includes drug dispensing and hospital records for > 2 million inhabitants in the Netherlands, new users of AHT > or = 18 years were identified for the period 1999-2004. Patients with elevated blood pressure (systolic BP > or = 140 and/or diastolic BP > or = 90 mmHg) within 6 months prior to onset of AHT treatment and a BP measurement within 6-12 months of treatment onset were included in the study cohort. Persistent AHT use was determined by summing the number of days of continuous treatment (gap between dispensings < 30 days) from start of treatment onwards. Patients with a BP below 140/90 mmHg at the first BP measurement within 6-12 months of treatment onset were defined as having attained goal. RESULTS: The study included 1271 patients with a mean systolic BP of 174 +/- 22 mmHg and a mean diastolic BP of 100 +/- 12 mmHg. Persistent AHT use was associated with a 40% increased chance of BP goal attainment (RR(adj) = 1.41; 95% CI: 1.08-1.85) after adjustment for gender, age, systolic blood pressure at start, and time to the BP measurement. CONCLUSION: Persistent use of AHT leads to increased blood pressure goal attainment in daily clinical practice.

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

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 > or = 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.

Treatment with inhaled corticosteroids in asthma is too often discontinued.

PURPOSE: To study persistence with inhaled corticosteroids (ICS) and its determinants in asthma-patients. METHODS: From the PHARMO database, asthma-patients (age < 35 years) with a first dispensing for ICS in 1999-2002 and > or = 2 dispensings in the first year were included. Persistence during the first year was defined as the number of days from start to time of first failure to continue renewal of the initial ICS. Potential determinants of persistence were assessed at ICS-start and 1 year before. RESULTS: The study-cohort included 5563 new users of single ICS and 297 of fixed-combined ICS. Less than 10% of patients using single ICS and 15% of patients using fixed-combined ICS were persistent at 1 year. Similar persistence-rates were observed when stratified for age (children/adolescents: 0-18 years and adults: 19-34 years). Increased persistence with single ICS was observed with the type of ICS (budesonide), prescriber (specialist), prior use of long-acting beta-agonists, previous hospitalization for asthma, metered-dose inhaler, low starting-dose and once-daily dosing regimen at start. Persistence with fixed combined ICS-treatment increased with younger age and was decreased in patients having high starting-dose of ICS and prior use of antibiotics. CONCLUSION: New users of both single and fixed combined ICS have alarming low persistence rates with ICS-treatment in the first year of follow-up. Persistence was mainly related to patient factors, such as severity of disease, and to treatment-related factors, such as once-daily dosing frequency.

Incidence of cardiovascular events in breast cancer patients receiving chemotherapy in clinical practice.

PURPOSE: To assess the incidence of cardiovascular events among breast cancer patients after chemotherapy. METHODS: Women > or =18 years with a breast tumour who received chemotherapy in 1992-2003 were selected from the PHARMO RLS. Chemotherapy with anthracyclines, a combination of anthracyclines and taxanes or second line treatment with trastuzumab was classified as cardiotoxic. Cardiovascular events were determined based on drug use and hospital admissions. Incidence rates of cardiovascular events and hazard ratios (HR) for the cardiotoxic versus non-cardiotoxic chemotherapy group were assessed during the first year and total follow-up. RESULTS: Of 648 patients with breast cancer included in the study cohort, 353 (54%) received cardiotoxic chemotherapy. At baseline, patients who received cardiotoxic chemotherapy compared with patients receiving non-cardiotoxic chemotherapy, received less anticoagulants/haemostatics (5 vs. 11%; p = 0.012) and had been less often hospitalised for cardiovascular disease (1 vs. 5%; p = 0.007) 2 years before the cohort entry date. After 1-year follow-up, the incidence rate of cardiovascular events was 69/1000 person years (py) for patients with cardiotoxic chemotherapy and 98/1000 py for patients with non-cardiotoxic chemotherapy, which did not differ significantly (HR 0.74 95% confidence interval (CI): 0.39, 1.41). After total follow-up, this was 81/1000 py for patients with cardiotoxic and 92/1000 py for patients with non-cardiotoxic chemotherapy (HR 0.81, 95%CI: 0.54, 1.20). CONCLUSIONS: This study showed similar cardiovascular incidence rates during follow-up for breast cancer patients treated with cardiotoxic and non-cardiotoxic chemotherapy. Specialists seemed to take pre-existing cardiovascular diseases into account when treating the breast cancer patient.

The effect of discontinuation of antihypertensives on the risk of acute myocardial infarction and stroke.

OBJECTIVE: Adherence to antihypertensive drug treatment is suboptimal. The present study investigates the effect of early treatment discontinuation with antihypertensive drugs on the risk of acute myocardial infarction (AMI) or stroke in daily clinical practice. METHODS: In the PHARMO Record Linkage System, which includes all records of drug dispensings and hospitalisations for > or = 2 million subjects in the Netherlands, new users of antihypertensive (AHT) drugs > or = 18 years of age were studied during the period 1 January 1993 - 1 October 2002 to determine the risk of AMI or stroke related to persistence with AHT. Patients were initially followed for 2 years to determine persistence with AHT, and then for a further 2 years or until the first hospital admission for AMI or stroke, death, or end of the study period. Patients using AHT for secondary prevention of cardiovascular disease were excluded from the study cohort. RESULTS: The study cohort included 77 193 AHT users. The percentage of non-persistent patients was 55% at 2 years, with the lowest non-persistence rates for angiotensin-receptor blockers (ARBs) and ACE-inhibitors (40%) and the highest rates for beta-blockers, calcium-channel blockers (CCBs) and diuretics (54-61%). Non-persistent AHT use was associated with a 15% increased risk of AMI (RR 1.15; 95% CI 1.00-1.33) and a 28% increased risk of stroke (RR 1.28; 95% CI 1.15-1.45). CONCLUSIONS: The results of this study show that in daily clinical practice early discontinuation of antihypertensive drug treatment in primary prevention increases the risk of subsequent AMI or stroke.

Enhanced persistence with tiotropium compared with other respiratory drugs in COPD.

BACKGROUND: Tiotropium is a once-daily inhaled anticholinergic maintenance treatment with demonstrated effectiveness in chronic obstructive pulmonary disease (COPD). OBJECTIVE: To compare persistence of tiotropium-use with other inhaled respiratory drugs in COPD in current clinical practice. METHODS: The PHARMO database includes, among others, drug-dispensing and hospital discharge records for 2> or = million subjects in the Netherlands. All probable COPD-patients were identified by new respiratory drug use (age >54 years) or COPD-hospitalisations. New users of tiotropium, ipratropium, long-acting beta-agonists (LABAs), or fixed combination of LABA and inhaled corticosteroids (LABA+ICS), in 1998-2003, were included in the study. Persistence was assessed quarterly during the first year of follow-up. Patients with a proportion of days covered (PDC) > or =80% were considered persistent. Persistence was analysed using generalised estimating equations model. RESULTS: About 37% of new users of tiotropium continued treatment for 1 year, compared with 14% for ipratropium, 13% for LABA, and 17% for LABA+ICS. Multivariate analyses showed that tiotropium-users were 2-3 times more persistent with their therapy than patients using ipratropium (relative risk [RR]: 2.0; 95% confidence interval [CI]: 1.8-2.3), LABA (RR: 2.9; 95% CI: 2.4-3.6), or LABA+ICS (RR: 2.4; 95% CI: 2.1-2.8), respectively. Sub-analyses in patients with a prior hospitalisation for COPD showed that 1-year persistence rates were increased for all treatments (varying from 33% for patients using LABA+ICS to 61% for patients using tiotropium), while persistence with tiotropium was again 2-3 times higher compared with other treatments. CONCLUSION: Persistence with tiotropium was higher compared to other inhaled respiratory drugs in COPD in clinical practice.

Higher persistence with valsartan compared with enalapril in daily practice.

OBJECTIVE: To compare persistence with valsartan and enalapril in daily practice. METHODS: The PHARMO Record Linkage System includes various data registries including drug dispensing and hospitalizations for > or =2 million subjects in the Netherlands. Patients newly treated with valsartan or enalapril in the period of 1999-2002 were selected. Persistence was calculated by summing up the number of days of continuous treatment. Patients who remained on therapy with valsartan or enalapril for 12 or 24 months were defined as persistent at 1 or 2 years, respectively. RESULTS: 3364 patients received valsartan and 9103 patients received enalapril. About 62% of patients treated with valsartan and 55% of patients treated with enalapril remained on therapy at 12 months after the initial dispensing, while 48% of patients treated with valsartan and 43% of patients treated with enalapril were persistent at 24 months. Patients treated with valsartan were about 20% more likely to stay on treatment than patients treated with enalapril (1 year RR(adj): 1.23, 95% CI: 1.16-1.32; 2 years RR(adj): 1.16, 95% CI: 1.11-1.23). CONCLUSIONS: Real-life persistence is higher with valsartan than with enalapril. The results of this and other studies on persistence in daily practice should be taken into account when deciding upon drug treatment for hypertension.

Persistence with antihypertensives related to formulation: the case of nifedipine.

BACKGROUND: Controlled-release dosage forms may enhance persistence with therapy because of reduced dosing frequency and fewer adverse effects. OBJECTIVE: To assess the differences in persistent use of nifedipine between once-daily nifedipine gastrointestinal therapeutic system (GITS) and twice-daily nifedipine retard formulations. METHODS: Incident nifedipine users were selected from January 1992 to December 2001 from the PHARMO database, including drug-dispensing records and hospital records of more than one million subjects in the Netherlands. Patients with unaltered formulation and dosing frequency of nifedipine in the first year of follow-up with at least 2 prescriptions were included in the cohort. Persistence with different formulations was assessed using Cox's proportional hazard analyses. Covariates included in the analysis were, among others, hospitalizations and comedication for cardiovascular diseases. RESULTS: In total, 5889 incident users of nifedipine were included. The median duration of the first treatment episode was 133 days for nifedipine retard and 262 days for nifedipine GITS. One-year persistence with nifedipine increased from 32% in patients using retard formulations to 44% in patients using nifedipine GITS. Multivariate analyses showed that patients using nifedipine GITS were 1.3 times (RR 1.33; 95% CI 1.22 to 1.46) more persistent than those using retard formulations of nifedipine. Persistent patients more often used other antihypertensive drugs and were more often hospitalized for cardiovascular diseases. CONCLUSIONS: Patients using once-daily nifedipine GITS are more persistent with therapy than patients using twice-daily retard formulations.

Selective prescribing of atypical antipsychotics.

PURPOSE: The aim of the study was to investigate whether the most recent introduced atypical antipsychotics olanzapine and risperidone were preferentially prescribed to patients susceptible to develop extrapyramidal side effects (EPS) and those not responding adequately to typical antipsychotics. METHODS: Data were obtained from the Dutch PHARMO system that includes complete medication and hospital admission records of 675 000 residents of 14 Dutch cities. A total number of 129 new users of olanzapine and 142 new users of risperidone as well as 507 new users of typical antipsychotic drugs were identified from our database in the period of 1996-1998. The prevalence of markers of EPS, therapy resistance and therapy non-compliance were assessed in the period of 1 year prior to a new start of an antipsychotic. RESULTS: New use of olanzapine and risperidone was significantly associated with previous use of other antipsychotics (odds ratio 4.0, 95%CI: 2.5-6.7 and odds ratio 3.0, 95%CI: 2.0-4.7, respectively). New use of olanzapine and risperidone was also associated with previous use of anticholinergic drugs compared to users of typical antipsychotics (over three and two times more, respectively). This effect diminished when adjusted for previous use of antipsychotics. CONCLUSIONS: In particular olanzapine and also risperidone were selectively prescribed to patients formerly treated with other antipsychotics and to those susceptible for EPS. If not recognised or controlled for, observational studies comparing different antipsychotic drugs may produce biased results on efficacy or frequency of side effects for the different types of antipsychotics.

Treatment patterns and health care costs of mebeverine-treated IBS patients: a case-control study.

BACKGROUND: Irritable bowel syndrome (IBS) is a functional disorder affecting the quality of life of patients. In the Netherlands, mebeverine is currently the only medical treatment registered for IBS, although its efficacy is considered disputable. OBJECTIVE: To assess treatment patterns and associated health care cost in mebeverine users relative to matched controls. METHODS: A matched case-control study was performed using pharmacy data. Cases were mebeverine users as proxy for IBS patients. Controls were non-mebeverine users and matched to cases by age, gender and pharmacy. Prevalence and incidence of mebeverine use, concomitant drug use and hospitalizations were assessed in 3431 cases and 3431 controls. Concomitant drug use and hospitalizations was also assessed in a subgroup of 1222 users of mebeverine and laxatives (proxy for constipation-IBS) and their controls. RESULTS: Twelve per 1000 residents were ever-dispensed mebeverine in 1998. One-third of these mebeverine users used laxatives concomitantly. Concomitant drug use and hospitalizations were increased in mebeverine users. The odds ratio for hospitalizations for gastrointestinal reasons was increased predominantly in mebeverine users with concomitant laxative use (OR:8.7; 95%CI [4.3-17.3]). Excess yearly costs for all concomitant medications were 94 Euros [95%CI 79 Euros-109 Euros] and for hospital admissions 120 Euros [74 Euros-166 Euros] per mebeverine user. In mebeverine users with concomitant laxative use these costs were 136 Euros and 251 Euros respectively. CONCLUSIONS: In treated IBS patients, concomitant drug use and hospitalizations are increased relative to matched controls. Medical resource use and associated health care costs are particularly increased in mebeverine users using laxatives. The total mean excess cost per patient per year is 482 Euros.