Effectiveness of HMG-CoA reductase inhibitors is modified by the ACE insertion deletion polymorphism.
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Aged↗
Biomedical subjects
Anthonius de Boer
Publications and source records attributed to Anthonius de Boer.
Acenocoumarol stabilization is delayed in CYP2C93 carriers.
OBJECTIVE: Our objective was to assess whether there is an association between the presence of allelic variants of the gene for cytochrome P450 (CYP) 2C9 and anticoagulation problems during the initial 3 to 6 months of acenocoumarol treatment. METHODS: A prospective follow-up study was performed at 2 anticoagulation clinics in the Netherlands. Included subjects started with a standard dose regimen as follows: 6 mg on the first day, 4 mg on the second day, and 2 mg on the third day. CYP2C9 genotypes were assessed, and data on international normalized ratio (INR), comedication, and comorbidity were collected. RESULTS: The CYP2C9 genotype of 231 subjects was assessed. Of these, 147 (63.6%) were wild-type subjects (CYP2C9*1/*1), 38 (16.5%) were carriers of CYP2C9*2, and 46 (19.9%) were carriers of CYP2C9*3. Compared with wild-type subjects, carriers of the CYP2C9*3 allele had (1) a lower chance to achieve stability in the first 6 months of therapy (hazard ratio, 0.62; 95% confidence interval, 0.42-0.91; P <.05) and (2) an increased risk of severe overanticoagulation (INR >6.0) (hazard ratio, 3.80; 95% confidence interval, 1.54-9.39; P <.01). For both outcomes, there was no significant difference between carriers of the CYP2C9*2 allele and wild-type subjects. CONCLUSION: In carriers of the CYP2C9*3 allele more difficulties in terms of stabilization and overanticoagulation were found as compared with wild-type subjects or CYP2C9*2 carriers. CYP2C9 genotyping could be useful to identify potential candidates for more frequent INR controls to minimize problems with acenocoumarol anticoagulation status.
Acenocoumarol↗
Effects of cytochrome P450 2C9 polymorphisms on phenprocoumon anticoagulation status.
OBJECTIVE: Our objective was to assess whether there is an association between the presence of allelic variants of the gene for cytochrome P450 (CYP) 2C9 and anticoagulation problems during the initial phase of phenprocoumon treatment. METHODS: A prospective follow-up study was performed at 2 anticoagulation clinics in The Netherlands. Included subjects started phenprocoumon during the study period, had their first check of the international normalized ratio (INR) on the third or fourth day of therapy, and had an indication for the low therapeutic range (INR, 2.0-3.5). CYP2C9 genotypes ( CYP2C9*1 , CYP2C9*2 , and CYP2C9*3 ) were assessed, and data on indication, INR checks, comedication, and comorbidity were collected. RESULTS: After genotyping, 284 subjects were available for analysis. Of these, 186 (65.5%) were homozygous carriers of the CYP2C9 wild-type allele ( CYP2C9*1/*1 ), 61 (21.5%) were carriers of the CYP2C9*2 allele, and 37 (13.0%) were carriers of the CYP2C9*3 allele. Compared with homozygous CYP2C9*1/*1 subjects, carriers of CYP2C9*2 or *3 had an increased risk of severe overanticoagulation (INR >6.0). The hazard ratio for CYP2C9*2 versus CYP2C9*1/*1 was 3.09 (95% confidence interval [CI], 1.56 to 6.13; P=.001), and the hazard ratio for CYP2C9*3 versus CYP2C9*1/*1 was 2.40 (95% CI, 1.03 to 5.57; P=.042). Carriers of CYP2C9*2 also had a lower chance to achieve stability in the follow-up period. The hazard ratio for CYP2C9*2 versus CYP2C9*1/*1 was 0.61 (95% CI, 0.43 to 0.85; P=.003). Carriers of the CYP2C9*2 or *3 allele needed a significantly lower phenprocoumon dosage compared with homozygous CYP2C9*1/*1 subjects. CONCLUSION: The presence of at least 1 CYP2C9*2 or *3 allele in phenprocoumon users is associated with an increased risk of severe overanticoagulation. Similar to warfarin and acenocoumarol, phenprocoumon had a lower dosage requirement in carriers of CYP2C9*2 or *3 compared with that in CYP2C9 wild-type subjects.
Aged↗
Comparison of two methodologies to analyze exposure to statins in an observational study on effectiveness.
OBJECTIVE: Estimates of efficacy of drugs from clinical trials may differ from estimates in observational studies. To obtain valid results, the definition of exposure in an observational study is critical. The objective of our study was to compare different exposure definitions for assessing the effectiveness of statins. STUDY DESIGN AND SETTING: The study was performed in the Rotterdam Study, a population-based cohort study that included 7983 subjects of > or =55 years of age. We selected 3806 subjects who received antihyperlipidemic drug treatment (n=179) or had a total cholesterol > or =6.5 mmol/L at baseline. We conducted analyses with two different exposure definitions. RESULTS: Treatment with statins was assessed at baseline. The adjusted relative risk (RR) of myocardial infarction (MI) and stroke was 0.75 (95% confidence interval [CI] 0.41-1.37) and of total mortality was 1.34 (95% CI 0.66-2.74) in subjects treated with statins. We used pharmacy data, which give insight into drug use on a continuous basis. The adjusted RR of MI and stroke after 2 years of cumulative treatment was 0.63 (95% CI 0.34-1.15) and of total mortality was 0.91 (95% CI 0.59-1.39). CONCLUSION: Our results suggest that use of a time-dependent exposure definition is more accurate because estimates of effectiveness were more in agreement with results from randomized controlled trials of statin treatment.
Aged↗
Pre-randomization decisions and group stratification in a randomized controlled trial to improve prescribing.
OBJECTIVE: To select and evaluate characteristics of primary care practice groups relevant for stratification prior to randomization. METHOD: Structured telephone interviews and pre- and post-intervention prescription data. SETTING: Additional study in an RCT to rationalize prescribing in primary care, addressing groups of pharmacists and doctors. Representatives of 61 primary care practice groups in the Netherlands. MAIN OUTCOME MEASURES: Identification and evaluation of primary care practice group characteristics related to changes in prescribing. These characteristics were evaluated by estimation of incidence rate ratios (Poisson regression). RESULTS: Of practice groups 40 representatives (66%) participated in our study. Three characteristics were found to be most relevant for stratification: the purpose of the practice groups (whether they participated in information exchange (n = 14) or binding consensus on pharmacotherapy (n = 26)), the use of a formulary (22 practice groups did and 18 groups did not) and the use of feedback data (22 groups did and 18 groups did not). These characteristics strongly modified the effect of the program on prescribing behaviour. While the overall effect of the program was to significantly reduce the prescribing of the targeted drugs, this change was not consistent in all strata. CONCLUSION: Assessment of the characteristics of practice groups made it possible to define factors to be used for a stratified randomization of practice groups which in retrospect indeed modified the effect of an educational intervention directed to change prescribing. Such pre-randomization assessments can be a useful tool in interventions designed to improve practice patterns in groups of physicians.
Communication↗
Decrease of antiparkinsonian drugs before start of an antipsychotic in patients on levodopa treatment?
INTRODUCTION: Antiparkinsonian drugs can induce behavioural disturbances, which should be treated by first reducing antiparkinsonian drugs and/or starting a benzodiazepine. If this approach fails, then antipsychotics can be considered. The aim of this study was to determine how often antiparkinsonian drugs are decreased and benzodiazepines are started in levodopa users before start of an antipsychotic drug. METHODS: Data came from the PHARMO database, which includes drug dispensing records for all residents of six Dutch cities. All patients were selected who had started antipsychotic drug therapy at least 360 days later than, and 180 days before the earliest and the latest dispensing date for levodopa in PHARMO respectively. For each patient who started an antipsychotic drug we randomly selected 2 matched controls who used levodopa for at least 540 days and who did not start an antipsychotic. We determined how many persons had reduced antiparkinsonian drug treatment (i.e., dosage decrement or discontinuation of an antiparkinsonian agent) or had started a benzodiazepine in the 180 days before the start of the antipsychotic or before a randomly chosen index date in the controls. RESULTS: We identified 40 antipsychotic starters and 64 matched controls. The prescribed daily dose of antiparkinsonian drug treatment was reduced in 14 antipsychotic starters (37%) and in 17 controls prior to the index date (27%) (relative risk 1.27, 95% confidence interval 0.77-2.08). Of these, 2 antipsychotic starters (5%) and 5 controls (8%) had started with a benzodiazepine (relative risk 0.73; 0.22-2.96). A further 34 antipsychotic starters (85%) and 49 controls (77%) returned later than expected to their community pharmacy before the index date (relative risk 1.43; 0.70-2.96). CONCLUSION: Our study demonstrates that the advice to reduce the levodopa dose or to start with a benzodiazepine when behavioural disturbances occur during levodopa treatment prior to the start of an antipsychotic, is not followed in daily practice.
Aged↗
Pharmacogenetics in health-care practice.
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Humans↗
The association between compliance with antihypertensive drugs and modification of antihypertensive drug regimen.
BACKGROUND: Non-compliance is an important factor in lack of control of blood pressure. Uncontrolled blood pressure, as well as patients' complaints about the prescribed medication, may lead to modification of the initially prescribed antihypertensive drug regimen. The objective of this study was to assess the association between non-compliance and change in medication regimen. METHODS: A nested case-control study within a cohort of new users of antihypertensive drugs between 1 January 1999 and 31 December 2002. We used data from the PHARMO database, a record linkage system containing drug-dispensing records from community pharmacies and linked hospital discharge records of approximately 950,000 subjects. Cases were subjects whose initial drug regimen was modified. Controls did not undergo such a modification. Conditional logistic regression was used to calculate odds ratios (OR) and their 95% confidence intervals (CI), and to adjust for confounders. RESULTS: In a cohort of 39,714 new users of antihypertensive drugs, we identified 11,937 cases and 11,937 matched controls. The percentage of non-compliant patients (compliance < 80%) among cases and controls was 5.1 and 3.6%, respectively [OR 1.39 (95% CI: 1.22-1.58)]. The association is stronger in females [OR 1.64 (95%CI: 1.37-1.94)] than in males [OR 1.14 (95% CI: 0.94-1.40)] and stronger if the duration of episode of use is longer than 6 months. CONCLUSION: Non-compliance is significantly associated with the occurrence of change in antihypertensive medication regimen. Pharmacists and physicians can use pharmacy data, although data tend to overestimate actual compliance, to assess and improve compliance with antihypertensive drugs, before modifying treatment regimens.
Aged↗
Pharmacoeconomic evaluation of testing for angiotensin-converting enzyme genotype before starting beta-hydroxy-beta-methylglutaryl coenzyme A reductase inhibitor therapy in men.
This study aimed to assess the potential cost-effectiveness of screening men for their angiotensin-converting enzyme (ACE)-genotype before starting statin therapy. We used a combination of decision-analytic and Markov modelling techniques to evaluate the long-term incremental clinical and economic effects associated with genetic testing of men with hypercholesterolemia before starting treatment with statins. The study was performed from a health care payer perspective. We used data from the Rotterdam study, a prospective population-based cohort study in the Netherlands, which was started in 1990 and included 7983 subjects aged 55 years and older. Men treated with cholesterol-lowering drugs at baseline or with a baseline total cholesterol > or = 6.5 mmol/l were included. The ratio of difference in lifelong costs between the screening strategy and the no screening strategy to difference in life expectancy between these strategies was calculated. We also performed a cost-utility analysis. The base case was a 55-year-old man with hypercholesterolemia who was initially untreated. Several univariate sensitivity analyses were performed. All costs were discounted with an annual rate of 5%. Screening men for their ACE-genotype was the dominant strategy for the base case analysis, because the screening strategy saved money (851 Euro), but life expectancy was not changed. Screening was the dominant strategy for all age-groups in our cohort. Even in 80-year-old subjects, with the shortest life-expectancy, it was cheaper to screen than to give lifelong treatment to men with a DD genotype without success. Even if all DD subjects were treated with other (non-statin) cholesterol-lowering drugs, screening remained the cost-effective strategy. The results of the cost-utility analysis were similar. Discounting the effects with 5% per year also had no major impact on the conclusions. If other studies confirm that men with the DD genotype do not benefit from treatment with statins, screening for ACE genotype in men most likely will be a cost-effective strategy before initiating statin therapy.
Anticholesteremic Agents↗
Recent trends in (under)treatment of hypercholesterolaemia in the Netherlands.
AIM: To assess recent trends in undertreatment of hypercholesterolaemia (1998-2002). METHODS: Data were obtained from the third cross-sectional examination of the Monitoring Project on Risk Factors for Chronic Diseases (n = 4878; age 31-70 years), conducted in the Netherlands. Treatment eligibility was established according to Dutch guidelines. Data from the second examination (1993-1997) were used to assess time trends. The association between demographic variables, cardiovascular disease risk factors, drug use and lipid-lowering medication was assessed using multivariable logistic regression. RESULTS: Overall, 45.9%[95% confidence interval (CI) 41.4, 50.4] of respondents eligible for treatment were treated, and 17.4% (95% CI 13.9, 20.9) were both treated and controlled (1998-2002). Treatment increased significantly after 1995, showed a slight decrease in subsequent years until 2000, when treatment increased again. Subgroups less frequently treated for primary prevention included among others males [odds ratio (OR) = 0.08; 95% CI 0.03, 0.21], younger patients (OR = 0.93 per year; 95% CI 0.88, 0.98), diabetics (OR = 0.19; 95% CI 0.07, 0.56), untreated hypertensives (OR = 0.21; 95% CI 0.09, 0.49) and current smokers (OR = 0.09; 95% CI 0.03, 0.25). In secondary prevention, patients with a history of stroke were less likely to receive treatment (OR = 0.41; 95% CI 0.18, 0.94) compared with patients with a history of ischaemic heart disease. CONCLUSIONS: Treatment of hypercholesterolaemia has steadily increased over the past 10 years in the Netherlands. However, at present still less than one out of two eligible for treatment is treated, and only about one out of six is both treated and controlled.
Adult↗
Failure to continue lipid-lowering drug use following the withdrawal of cerivastatin.
BACKGROUND: Persistence with lipid-lowering drug use is important in order for patients to gain full treatment benefit. The withdrawal of cerivastatin from the market may have affected persistence due to the fear of serious adverse effects. OBJECTIVE: To assess failure of patients to continue lipid-lowering drug use following the withdrawal of cerivastatin. METHODS: A cohort study including 3.5 months follow-up after the withdrawal of cerivastatin in August 2001 was conducted using data from community pharmacies in The Netherlands, covering a population of approximately 600,000 subjects. Patients selected for inclusion in the index group were current users of cerivastatin on August 10, 2001 (the date that cerivastatin was withdrawn from the market). Reference patients were gender, age and pharmacy or region matched patients who were using any HMG-CoA reductase inhibitor other than cerivastatin on the same date. The main outcome measure was discontinuation of lipid-lowering drug use. To assess whether discontinuation had increased in the reference group, discontinuation rates were compared with discontinuation rates in the previous year. Data on these rates in 2000 were obtained from the population-based PHARMO record linkage system. RESULTS: A total of 31 pharmacies of the research network (response rate 86.1%) provided medication histories of 234 current users of cerivastatin and 431 matched patients using any other HMG-CoA reductase inhibitor. In addition, 352 current users of cerivastatin and 704 matched patients using any other HMG-CoA reductase inhibitor were obtained from the PHARMO database. Overall, 13.7% of subjects in the cerivastatin group (n=586) and 9.5% in the reference group (n=1135) discontinued lipid-lowering medication (adjusted odds ratio [OR] 1.44; 95% CI 1.04-2.00). The rate of discontinuation in the reference group was comparable to this rate in the previous year. Discontinuation was more prevalent in women who had been taking cerivastatin (adjusted OR 1.74; 95% CI 1.09-2.78), those receiving low doses of cerivastatin (adjusted OR 2.45; 95% CI 1.20-4.97), those who received their last cerivastatin prescription from a specialist (adjusted OR 1.92; 95% CI 1.02-3.60) and those who had recently started using cerivastatin (adjusted OR 2.80; 95% CI 0.98-7.98), although the latter was not statistically significant. CONCLUSIONS: Failure to continue lipid-lowering drug use was higher in patients using cerivastatin than in users of other HMG-CoA reductase inhibitors, especially in women, those using low doses of HMG-CoA reductase inhibitors and recent starters of lipid-lowering medication. The prevention of unwarranted discontinuation of drugs due to market withdrawal should be a joint task of healthcare providers, industry and regulatory bodies.
Adult↗
Polymorphic drug metabolism (CYP2D6) and utilisation of psychotropic drugs in hospitalised psychiatric patients: a retrospective study.
AIM: The aim of the current retrospective study was to assess the influence of polymorphic drug metabolism as assessed by genotyping, on the on the utilisation of psychotropic drugs in hospitalised psychiatric patients. The utilisation of psychotropic drugs was assessed using pharmacy records with emphasis on the number of prescriptions and prescriptions for possible side effects. METHODS: CYP2D6 genotype was assessed in 241 psychiatric patients by investigation for the five most common allelic variants ( CYP2D6*3, *4, *6, *7, *8) and the presence of gene duplication using allele-specific polymerase chain reaction. Data concerning the pharmacotherapy of the patients were retrieved from the pharmacy information system. Data was analysed on differences observed in pharmacy records concerning the different metabolic classes: ultra rapid metabolisers (UMs), extensive metabolisers (EMs) and poor metabolisers (PMs). RESULTS: For CYP2D6, 2.5% was UM (95% CI: 0.5-4.5%, n=6) and 8.3% was PM (95% CI: 4.8-11.8%, n=20). Drugs metabolised by CYP2D6 were less frequently prescribed in PMs than EMs (21.1% vs 33.6%, P=0.023). The average duration of prescriptions was significantly lower in PMs than EMs (54 days vs 106 days, P=0.010). Between UMs and EMs, no significant differences were found, although a similar tendency was observed. With regard to dose, no consistent differences were observed between the CYP2D6 genotype classes. Drugs against Parkinsonian-like side effects were given twice as frequently in PMs as EMs (6.9% vs 3.4%, P=0.045). CONCLUSIONS: Patients with impaired CYP2D6 metabolism received fewer CYP2D6 drugs. PMs were more prone to Parkinsonian-like side effects as evidenced by more prescriptions for drugs combating these side effects. Dose titrations were not often used to compensate for genetic polymorphisms. Pharmacy records might be a useful tool to detect differences related to polymorphic metabolism.
Adult↗
Repeated nitrate prescriptions as a potential marker for angina pectoris. A comparison with medical information from the Rotterdam Study.
OBJECTIVE: The objective of this study was to determine whether pharmacy records of nitrate prescriptions could be used as a marker of angina pectoris. METHOD: This study was conducted within the Rotterdam Study, a prospective follow-up study which started in 1991 and included 7983 elderly subjects. During follow-up, 1601 subjects filled a first prescription for a nitrate and later filled at least one other prescription for nitrates according to pharmacy records. After excluding subjects who started using nitrates in 1991 and who had less than one year of medication history, we took a random sample of 78 subjects (10%). We studied discharge and outpatient cardiologist letters and files from general practitioners for additional information on angina pectoris in these subjects, and allocated patients to one of three categories according to the possibility of the initial diagnosis of angina being correct. RESULTS: From the random sample of 78, additional information was available on 75 subjects. Definite angina pectoris was present in 33, probable angina pectoris in 18, and possible angina pectoris in 19 subjects. Five subjects had no angina pectoris. Therefore, 93% had at least a possible diagnosis while 68% had at least a probable diagnosis of angina pectoris. The positive predictive value of 2 nitrate prescriptions of which at least one was for rescue therapy was 94%. CONCLUSIONS: We conclude that the use of more than one nitrate prescription can be used as a marker for angina pectoris. This marker may be useful in epidemiological studies.
Aged↗
Adherence to and dosing of beta-hydroxy-beta-methylglutaryl coenzyme A reductase inhibitors in the general population differs according to apolipoprotein E-genotypes.
Discontinuation and poor adherence to therapy are major problems during long-term treatment, particularly with cholesterol lowering drugs. Several studies have indicated that the cholesterol lowering effect of statins differs according to apolipoprotein (apo)E genotypes. Low-density lipoprotein-cholesterol lowering capacity appears to be smaller in subjects with the epsilon(4) allele. To assess whether the use of statins in daily practice differs according to apoE genotypes, we used data from the Rotterdam Study, a population-based prospective cohort study in the Netherlands, which started in 1990 and included 7983 subjects aged 55 years or more. During follow-up, there were 798 subjects who started to use statins. We used a Cox proportional hazard model to determine the rate of discontinuation in the first 3 years of statin use. Subjects on statin therapy with epsilon(2)epsilon(2) and epsilon(4)epsilon(4) genotypes showed a trend towards higher dosages than subjects with the other genotypes. Relative to subjects with the epsilon(2)epsilon(3) genotype, those with the epsilon(4)epsilon(4) genotype had a risk of 2.28 [95% confidence interval (CI) 1.02-5.12] to discontinue statins within 3 years. In women, this relative risk was 1.70 (CI 0.53-5.42) versus 3.18 (CI 1.01-10.03) in men. The apoE genotype is associated with discontinuation of statins. This suggests that subjects who are genetically prone to develop hypercholesterolemia show the highest risk of discontinuation of treatment.
Apolipoproteins E↗
Oral antithrombotic use among myocardial infarction patients.
OBJECTIVE: To examine the use of oral antithrombotics (i.e., antiplatelet agents, oral anticoagulants) after myocardial infarction (MI) in the Netherlands from 1988 to 1998. METHODS: Retrospective follow-up of 3800 patients with MI, using data from the PHARMO Record Linkage System. RESULTS: From 1988 to 1998, oral antithrombotic treatment increased significantly from 54.0% to 88.9%. In 1998, only 75.8% of patients who experienced a MI in the late 1980s received oral antithrombotic treatment compared with 94.4% of those who experienced a recent MI. CONCLUSIONS: Oral antithrombotics were considerably underused in patients with a past history of MI. Therefore, these patients should be reviewed for antithrombotic therapy to assess whether their failure to use oral antithrombotics was right or wrong, and whether treatment should be initiated if possible.
Administration, Oral↗
Drug therapy for prevention of recurrent myocardial infarction.
OBJECTIVE: To provide an evidence-based overview of drug treatment for long-term secondary prevention of myocardial infarction (MI). DATA SOURCES: We conducted searches of MEDLINE (1966-August 2002), the Cochrane Controlled Trial Register, and the reference list of each identified study. STUDY SELECTION/DATA EXTRACTION: Trials and meta-analyses were included using the following criteria: (1) randomized trials, (2) description of identification procedure, inclusion criteria, outcome measures, and statistical methods, (3) confirmed MIs, (4) treatment continued for at least 1 month, and (5) all-cause mortality as primary outcome; other events as secondary outcomes. All authors interpreted the results from trials that met the inclusion criteria. DATA SYNTHESIS: In randomized clinical trials, low-dose aspirin, high-intensity oral anticoagulants, beta-blockers, angiotensin-converting enzyme (ACE) inhibitors, and statins decreased the risk of mortality and reinfarction after MI. Randomized clinical trials using calcium-channel blockers, antiarrhythmics, and hormone replacement therapy did not show benefits in patients with prior MI. Effects of the combined use of aspirin or oral anticoagulants with beta-blockers or ACE inhibitors plus statins must be derived from subgroup analysis of trials, but seem to be beneficial. CONCLUSIONS: The use of at least aspirin or an oral anticoagulant, a beta-blocker or an ACE inhibitor, plus a statin should be incorporated in the treatment routine. Clopidogrel treatment might be an alternative to aspirin. Standard addition of a beta-blocker to ACE inhibitor-treated patients without reduced left-ventricular ejection fraction seems to be untimely.
Evidence-Based Medicine↗
Genetic polymorphisms: importance for response to HMG-CoA reductase inhibitors.
Coronary artery disease is among the leading causes of death worldwide. Clinical trials show a protective effect of statins against the sequelae of coronary artery disease. The mean risk reductions for subjects using statins compared with placebo found in these trials is about 30%. These are average reductions for all patients included in the trials. Important factors in interpreting the variability in the outcome of drug therapy include the patient's health profile, prognosis, disease severity, quality of drug prescribing, compliance with prescribed pharmacotherapy and the genetic profile of the patient. This review aims to give an overview of the known polymorphisms (Cholesteryl Ester Transfer Protein polymorphism, Stromelysin-1 polymorphism, -455G/A and TaqI polymorphisms of the beta-fibrinogen gene, apoE4, Asp(9)Asn mutation in the lipoprotein lipase gene, the -514 CT polymorphism in the hepatic lipase gene and the ACE deletion type gene) that have an influence on the effects of statins in the general population. The expectation is that in the future a subject's genotype may determine whether he will be treated with statins or not. Determining the genotype will not deny therapy to a subject, but will help in deciding the therapy that will suit the patient best.
Apolipoprotein E4↗
Time trends in lipid lowering drug use in The Netherlands. Has the backlog of candidates for treatment been eliminated?
AIMS: To assess time trends in lipid lowering drug use in The Netherlands. METHODS: Data were obtained from the PHARMO-database, comprising pharmacy records of approximately 300 000 people in The Netherlands. In the period from 1991-98, we estimated prevalence of lipid lowering drug use on the first Wednesday of October. A patient was defined as incident user if (s)he filled a prescription for lipid lowering medication after a 360 days lipid lowering drug free interval. Both prevalence and incidence estimates were weighted for the sex and age distribution of the general Dutch population. RESULTS: From 1991 to 1998, the prevalence of lipid lowering drug use increased from 0.5% (95% confidence interval (CI): 0.5, 0.6) to 2.3% (95% CI: 2.2, 2.4) in women and from 0.6% (95% CI: 0.6, 0.6) to 2.9% (95% CI: 2.8, 3.0) in men. Prevalence increased with increasing age and was highest in the age category 60-69 years (in 1998: 9.9% (95% CI: 9.4, 10.4) in women and 11.6% (95% CI: 11.0, 12.1) in men). In 1992, the estimated incidence of lipid lowering drug use was 251(95% CI: 226, 277)/100,000 person years in women and 251(95% CI: 225, 276)/100,000 person years in men. The largest incidence estimates were observed in 1996 (685(95% CI: 644, 726)/100,000 person years in women and 881(95% CI: 834, 928)/100,000 person years in men). After 1996, incidence stabilized in 1997 and decreased in 1998 to 599(561, 637)/100,000 person years in women and 731(688, 773)/100,000 person years in men. Most of the patients (approximately 95%) were treated with one lipid lowering agent. Statins were used by over 90% of patients from 1996 onwards. In 1998, 35% of the patients started with a statin that was not a first choice drug (mainly atorvastatin). CONCLUSIONS: In the period from 1991-98, prevalence of lipid lowering drug use significantly increased in The Netherlands. However, incidence stabilized and decreased after 1996 which may be explained by the fact that the number of patients eligible for treatment was reached. The question remains whether lipid lowering medication was targeted to the appropriate patients.
Age Factors↗