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Anthonius de Boer

Publications and source records attributed to Anthonius de Boer.

At least 19 recordsLinked to original sources

The influence of the alpha-adducin G460W polymorphism and angiotensinogen M235T polymorphism on antihypertensive medication and blood pressure.

Despite the availability of a variety of effective antihypertensive drugs, inadequate control of blood pressure is common in hypertensive patients. The aim of this study was investigate whether the alpha-adducin G460W polymorphism or angiotensinogen M235T polymorphism has an effect on the mean difference in blood pressure in subjects using antihypertensive drugs. Data from the Rotterdam Study, a population-based prospective cohort study in the Netherlands, was used. This study started in 1990 and included 7983 subjects of 55 years and older. Data from three examination rounds were used. Subjects were included when their blood pressure was elevated at 1 or more examinations and/or a diuretic, beta-blocker, calcium antagonist, or ACE inhibitor was used. A marginal generalized linear model was used to assess the drug-gene interaction. In total, 3025 hypertensives were included. No drug-gene interaction on blood pressure levels was found. The mean difference in systolic blood pressure (SBP) between subjects with the W-allele and GG genotype of the alpha-adducin gene was for diuretic users 1.25 mmHg (95% CI:-2.86 to 5.35), for beta-blockers 0.02 mmHg (95% CI:-3.39 to 3.42), for calcium antagonists -0.70 mmHg (95% CI:-5.61 to 4.21), and for ACE inhibitors -3.50 mmHg (95% CI:-9.02 to 2.02). The mean difference in SBP between subjects with the TT and MM genotype was for diuretic users -2.33 mmHg (95% CI:-8.32 to 3.66), for beta-blocker -0.06 mmHg (95% CI:-4.91 to 4.79), for calcium antagonist 0.59 mmHg (95% CI:-5.95 to 7.13), and for ACE inhibitor -2.33 mmHg (95% CI:-9.66 to 5.01). The G460W polymorphism and the M235T polymorphism did not modify the difference in blood pressure levels among subjects who used diuretics, beta-blockers, calcium antagonists, or ACE inhibitors.

Adrenergic beta-Antagonists↗

Drug-gene interaction between the insertion/deletion polymorphism of the angiotensin-converting enzyme gene and antihypertensive therapy.

BACKGROUND: Despite the availability of a variety of effective drugs, inadequate control of blood pressure is common. There are some indications that the angiotensin-converting enzyme (ACE) gene modifies the response to antihypertensive drugs, but the results have been inconclusive. OBJECTIVE: To investigate whether the insertion/deletion polymorphism of the ACE gene modifies blood pressure differences among subjects using diuretics, beta-blockers, calcium-channel antagonists, or ACE inhibitors. METHODS: Data were used 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 older. Data from 3 subsequent cross-sectional investigations were used, as well. Subjects were included if they had high blood pressure during one or more examinations and/or used monotherapy with a diuretic, beta-blocker, calcium-channel antagonist, or ACE inhibitor. A marginal, generalized, linear model was used to assess the association between the mean difference in systolic/diastolic blood pressure and antihypertensive classes stratified by the 3 genotypes. RESULTS: In total, 3025 hypertensive individuals were included, and 6500 measurements of blood pressure were taken. The percentages of DD, ID, and II genotypes were 28.3%, 51.4%, and 20.3%, respectively. The mean differences in systolic blood pressure between the II and DD genotypes were 0.23 mm Hg (95% CI -5.48 to 5.94) for diuretics, -2.41 mm Hg (95% CI -6.72 to 1.90) for beta-blockers, 2.12 mm Hg (95% CI -4.64 to 8.89) for calcium-channel antagonists, and -2.01 mm Hg (95% CI -9.82 to 5.79) for ACE inhibitors. CONCLUSIONS: The adjusted mean difference in diastolic and systolic blood pressure among diuretic, beta-blocker, calcium-channel antagonist, or ACE inhibitor users was not modified by the ACE insertion/deletion polymorphism.

Aged↗

Initial non-compliance with antihypertensive monotherapy is followed by complete discontinuation of antihypertensive therapy.

PURPOSE: Discontinuation with treatment is a major problem in the treatment of hypertension. The objective of our study was to assess the association between non-compliance and discontinuation in patients who started using antihypertensive monotherapy. METHODS: A nested case-control study within a cohort of new users of antihypertensive drugs between 1st January 1999 and 31st December 2002 was performed. 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 discontinued their use of antihypertensive monotherapy and were not switched to other antihypertensive treatment, controls stayed on their initially prescribed monotherapy. Conditional logistic regression was used to calculate odds ratios (OR) and their 95% confidence intervals (CI). RESULTS: In a cohort of 39,714 new users of antihypertensive drugs, we identified 9111 cases and 9111 matched controls. The percentage of non-compliant patients (compliance < 80%) among cases and controls was 14.0% and 5.8%, respectively [OR 2.86 (95%CI: 2.52-3.24)]. Patients who used less than 90 days had a higher risk on discontinuation [OR 3.10 (95%CI: 2.67-3.59)] than patients who used more than 90 days [OR 2.28 (95%CI: 1.79-2.92)]. The association was generally similar among males and females, among the different types of antihypertensives and among the different age groups. CONCLUSION: In patients who start antihypertensive monotherapy, non-compliance is often followed by discontinuation of this antihypertensive treatment. The pharmacy medication history is a valuable tool for physicians to identify patients who have a high risk on discontinuation with antihypertensive treatment.

Adolescent↗

Discrepancies between medication records of anticoagulation clinics and pharmacy records.

PURPOSE: To determine whether there were discrepancies between with coumarin anticoagulants interacting medications recorded in medical files of anticoagulation clinics (AC-records) and computerized records of community pharmacies (pharmacy records). METHODS: A descriptive study was conducted at two Dutch anticoagulation clinics (AC's). Records of with coumarin anticoagulants interacting drugs at the AC's were compared with the pharmacy records. A drug registered in the pharmacy records but not in the AC-records, was recorded as a discrepancy, while a drug registered in AC-records as well as in pharmacy records, was recorded as a match. RESULTS: Of the 117 identified interacting drugs registered in pharmacy records 32 (27%) were not registered in the AC-records. In four out of seven patients of whom the use of a pharmacokinetically interacting drug was not registered in the AC-records, several INR-values exceeded the upper therapeutic range. CONCLUSION: This study demonstrates that a substantial percentage of drugs of which an interaction with coumarin anticoagulants can be expected, is not registered in the medical files of anticoagulation clinics.

Aged↗

VKORC1 and CYP2C9 genotypes and acenocoumarol anticoagulation status: interaction between both genotypes affects overanticoagulation.

OBJECTIVE: Our objective was to assess the effects of VKORC1 and CYP2C9 genotypes on severe overanticoagulation and time to achieve stability and their contributions to dose requirement during the initial phase of acenocoumarol treatment. METHODS: A prospective follow-up study was conducted at 2 anticoagulation clinics in The Netherlands. We assessed the CYP2C9 genotype (CYP2C9*2 and CYP2C9*3 polymorphisms) and the VKORC1 C1173T genotype of the subjects and collected data on international normalized ratio, dose, comedication, and comorbidity. RESULTS: Of the 231 patients in the cohort, 150 (64.9%) had a VKORC1 C1173T polymorphism and 84 (36.4%) had a CYP2C9*2 or CYP2C9*3 allele. Only carriers of a combination of a CYP2C9 polymorphism and a VKORC1 polymorphism had an increased risk of severe overanticoagulation compared with subjects with no polymorphism or only 1 polymorphism (hazard ratio, 3.83 [95% confidence interval, 1.62-9.05]). The time to achieve stability was associated with the possession of the CYP2C9 genotype, not with the VKORC1 genotype (hazard ratio for CYP2C9*3 allele compared with CYP2C9 wild type, 0.59 [95% confidence interval, 0.40-0.87]). Patients with a VKORC1 polymorphism required significantly lower doses than VKORC1 CC wild-type patients. A larger part of the variability in dose requirement was explained by the VKORC1 genotype than by the CYP2C9 genotype (21.4% and 4.9%, respectively). CONCLUSION: Being a carrier of a combination of polymorphisms of VKORC1 and CYP2C9, rather than of one of these polymorphisms, is associated with severe overanticoagulation. The time to achieve stability is mainly associated with the CYP2C9 genotype.

Acenocoumarol↗

Instrumental variables: application and limitations.

To correct for confounding, the method of instrumental variables (IV) has been proposed. Its use in medical literature is still rather limited because of unfamiliarity or inapplicability. By introducing the method in a nontechnical way, we show that IV in a linear model is quite easy to understand and easy to apply once an appropriate instrumental variable has been identified. We also point out some limitations of the IV estimator when the instrumental variable is only weakly correlated with the exposure. The IV estimator will be imprecise (large standard error), biased when sample size is small, and biased in large samples when one of the assumptions is only slightly violated. For these reasons, it is advised to use an IV that is strongly correlated with exposure. However, we further show that under the assumptions required for the validity of the method, this correlation between IV and exposure is limited. Its maximum is low when confounding is strong, such as in case of confounding by indication. Finally, we show that in a study in which strong confounding is to be expected and an IV has been used that is moderately or strongly related to exposure, it is likely that the assumptions of IV are violated, resulting in a biased effect estimate. We conclude that instrumental variables can be useful in case of moderate confounding but are less useful when strong confounding exists, because strong instruments cannot be found and assumptions will be easily violated.

Bias↗

Prescribing behaviour according to Dutch and European guidelines on the management of hypercholesterolaemia (1992-1999).

BACKGROUND: The success of the full implementation of a new guideline may depend on the observed discrepancy between daily medical practice developed before the release of the guideline and new treatment recommendations issued by the guideline. AIM: To assess whether the initiation of statin treatment for primary prevention of cardiovascular disease in an elderly population was in agreement with guidelines. METHODS: Data were obtained from the Rotterdam Study, a prospective population-based cohort study consisting of 7983 subjects aged>or=55 years. In the period 1992-1999, all patients starting statins for primary prevention were selected. Treatment eligibility was established according to Dutch guidelines based on considerations of cost effectiveness (1998) and European guidelines based on clinical effectiveness (1998 and 2003). RESULTS: Only 5.7% [95% confidence interval (CI) 3.1, 8.3] of the 299 subjects starting statins for primary prevention met the eligibility criteria of the Dutch guidelines. Most patients (92.0%, 95% CI 88.9, 95.1) met the criteria of the 2003 European guidelines. Patients who did not meet any eligibility criteria were female and had one or less cardiovascular risk factor, except for two patients with total cholesterol levels<5 mmol l-1 prior to start of statin therapy. CONCLUSIONS: The use of statins was in agreement with the most recent European guidelines in over 90% of elderly patients who started statins for primary prevention, but in only 6% of these patients according to the Dutch guidelines. As long as existing guidelines are as discrepant as they are now, variation in agreement between physicians' prescribing and guideline recommendations is unavoidable.

Adult↗

Improving pharmacotherapy after myocardial infarction by group academic detailing using feedback data on a patient level.

STUDY OBJECTIVE: To develop and evaluate a peer review group (PRG) meeting using feedback data on a patient level to improve the quality of drug therapy for prevention of recurrent myocardial infarction. DESIGN: Prospective follow-up study. DATA SOURCE: General practitioners' computerized patients records (intervention patients) and the PHARMO record linkage system (controls). PATIENTS: Forty patients in the intervention group and 1030 control patients; both groups had documented myocardial infarction. INTERVENTION: The intervention, which was based on the principles of group academic detailing, consisted of scoring current cardiovascular treatment on separate forms for each patient, presenting an overview of, and discussing, evidence-based treatment after myocardial infarction, defining the target population, formulating a binding consensus, and identifying patients who were eligible for improvement of pharmacotherapy. MEASUREMENTS AND MAIN RESULTS: Drug therapy and adherence to the newly formulated PRG consensus were assessed at baseline and 1 year after the intervention. Of the patients who received the intervention and were not treated according to the PRG consensus at baseline, 40% received treatment according to the consensus 12 months after the PRG meeting. In the control group, the proportion of patients was 9.5% (prevalence ratio 4.2, 95% confidence interval 1.8-9.7). CONCLUSION: Peer review group meetings can be a valuable tool for improving pharmacotherapy after myocardial infarction.

Aged↗

A comparison of two multiple-characteristic decision-making models for the comparison of antihypertensive drug classes: Simple Additive Weighting (SAW) and Technique for Order Preference by Similarity to an Ideal Solution (TOPSIS).

BACKGROUND: Multiple-characteristics decision-making (MCDM) models can be used to calculate a score, based on a set of characteristics, for a number of alternative drugs or drug classes to allow comparison between them and thus enhance evidence-based pharmacotherapy. OBJECTIVE: To compare two MCDM models, Simple Additive Weighting (SAW) and Technique for Order Preference by Similarity to an Ideal Solution (TOPSIS), in determining first-line antihypertensive drug class. METHODS: Five different classes of antihypertensive drugs were analyzed: diuretics, beta-adrenoceptor antagonists (beta-blockers), dihydropyridine calcium channel blockers (DHP-CCBs), ACE inhibitors, and angiotensin II type 1 receptor antagonists (angiotensin receptor blockers [ARBs]). Four characteristics were deemed relevant for the determination of first-line antihypertensive drug class: effectiveness, persistence with treatment as a measure of tolerability, cost, and clinical experience. Weight factors were determined by sending questionnaires to cardiologists, pharmacists, general practitioners (GPs), and internists in The Netherlands. Absolute scores for the characteristics were determined from literature (effectiveness and persistence) and health insurance data (costs and clinical experience). RESULTS: Ninety-two cardiologists (33% of those sent the questionnaire), 90 GPs (31%), 87 internists (31%), and 123 pharmacists (43%) completed the questionnaire. Among all professions, according to both SAW and TOPSIS, ACE inhibitors were ranked as the first-line antihypertensive drug class, typically followed by beta-blockers. CONCLUSION: Both SAW and TOPIS analyses, using weight factors assigned by cardiologists, pharmacists, GPs, and internists from The Netherlands, rank ACE inhibitors as the first choice among antihypertensive drug classes for the treatment of uncomplicated hypertension. Both methods are valuable tools in the development of evidence-based pharmacotherapy.

Adrenergic beta-Antagonists↗

Generic substitution of antihypertensive drugs: does it affect adherence?

BACKGROUND: Generic substitution is an important opportunity to reduce the costs of pharmaceutical care. However, pharmacists and physicians often find that patients and brand-name manufacturers have doubt about the equivalence of the substituted drug. This may be reflected by decreased adherence to therapy. OBJECTIVE: To assess the association between generic substitution and nonadherence to antihypertensive drugs. METHODS: We conducted a matched cohort study between January 1, 1999, and December 31, 2002. Data were obtained from PHARMO, a record linkage system containing drug-dispensing records from community pharmacies and linked hospital discharge records of approximately 950,000 people in The Netherlands. Residents of 30 medium-sized cities who initiated antihypertensive drug therapy were potential subjects. Refill adherence with antihypertensive drugs after substitution was determined; those with refill adherence below 80% were considered nonadherent. RESULTS: Four hundred sixty-three patients with a substitution in therapy and 565 controls, matched on age, gender, therapy start date, duration of use, and generic product code, were identified. Of the patients who switched from brand-name to generic formulations ("substituted"), 13.6% were nonadherent, and of the non-substituted patients (those who did not switch to generic), 18.7% were nonadherent (OR 0.68; 95% CI 0.48 to 0.96). The association was absent in males. None of the patients discontinued the medication. No differences in hospitalizations for cardiovascular disease in the 6 months after the substitution were observed. CONCLUSIONS: Generic substitution of antihypertensive drugs does not lead to lower adherence or more discontinuation and cardiovascular disease-related hospitalizations compared with brand-name therapy. When a less-expensive antihypertensive generic equivalent becomes available, generic substitution should be considered to achieve economic benefits.

Adult↗

Refill persistence with chronic medication assessed from a pharmacy database was influenced by method of calculation.

BACKGROUND AND OBJECTIVES: In literature, different methods of calculating persistence are used. In this study, the effect of using these different methods on persistence and the association of patients characteristics and persistence are assessed. METHODS: The PHARMO record linkage system was used to calculate persistence with antihypertensive drugs for a cohort of 14,466 new users of antihypertensives. Three different types of methods were used to define the maximum gap allowed between two prescriptions that a patient may have to be defined as a continuous user, one based on a defined number of days (varying from 9-365 days), the second based on the duration of the last prescription (varying from 0.1-4 times the duration), the third based on a combination of both methods, whichever leads to the lowest number of days. RESULTS: Refill persistence varied between 19.7-86.4% (method 1), between 27.9-90.2% (method 2), and between 19.7-86.4% (method 3). Furthermore, patient characteristics associated with persistence differed between and within the three different methods. CONCLUSION: The method used and the variation within a method influenced both persistence and the association between patient characteristics and persistence. Results of persistence studies are highly influenced by the researchers' method of the maximum allowed treatment gap.

Adolescent↗

Effectiveness of interventions by community pharmacists to improve patient adherence to chronic medication: a systematic review.

OBJECTIVE: To systematically review the impact of interventions by community pharmacists on patients' adherence with chronic medication. DATA SOURCES: A MEDLINE search (1966-November 30, 2003) and a review of reference sections were done to identify all pertinent English- and German-language journal articles. Search terms included compliance, adherence, persistence, discontinuation, pharmacist, and intervention. STUDY SELECTION AND DATA EXTRACTION: From each relevant study, the following data were extracted: study design, country, disease, number of patients, patients' age and gender, type of intervention, duration of follow-up, method of measurement of adherence and adherence rate, and data concerning the quality of the included studies. DATA SYNTHESIS: A total of 162 studies were identified, of which 18 matched our inclusion criteria. Twelve were randomized controlled trials and 6 were non-crossover single-group trials. Eight studies showed significant improvement of adherence at one or more time points. Eight studies did not show any effect, 7 of which were randomized controlled trials. In most studies, adherence rates at baseline were high compared with rates reported in the general population. Counseling, monitoring, and education during weekly or monthly appointments showed some effect. However, these same types of interventions showed no effect in other studies. The overall quality of the included studies was low. CONCLUSIONS: Currently, it is impossible to identify an overall successful adherence-improving strategy performed by pharmacists. More well-designed and well-conducted studies on the effectiveness of interventions by a community pharmacist to improve patient adherence to chronic medication need to be performed.

Community Pharmacy Services↗

Discontinuation of rivastigmine in routine clinical practice.

BACKGROUND: Rivastigmine is used for symptomatic treatment of mild-to-moderately severe Alzheimer's Dementia (AD). We investigated the frequency of and reasons for rivastigmine discontinuation in clinical practice and possible predictive factors for discontinuation within the first six months after starting therapy. METHODS: A retrospective cohort study was performed in rivastigmine users, who started therapy in a naturalistic setting. A nurse supported a part of the studied cohort, as this was introduced during the study period. Reasons for discontinuation were investigated, including therapy discontinuation if the Maximum Achieved Dose (MAD) was below 6 mg daily. Predictors of discontinuation within the first half year were investigated by logistic regression analysis. RESULTS: Baseline Mini-Mental-State-Examination (MMSE) of included patients (n = 154) was 20.1, mean age was 78.4 years and 70% was female. Within 6 months, 61 users (39.6%) discontinued therapy, primarily (59.0%) for adverse events. Thereafter, the main reason for discontinuation was non-response according to clinimetrics. A MAD during the titration phase of 1.5-4.5 mg/day and absence of nurse support are significantly related to discontinuation within 6 months. CONCLUSIONS: Rivastigmine is primarily discontinued within the first six months for intolerable adverse events and thereafter mainly for ongoing deterioration. A MAD of 1.5-4.5 mg/day and the absence of nurse support are independently related to discontinuation of rivastigmine within the initial 6 months.

Aged↗

Cardiovascular drug use and differences in the incidence of cardiovascular mortality in elderly Serbian men.

OBJECTIVE: To assess whether the difference in risk of cardiovascular mortality between urban and rural areas of Serbia could be explained by differences in the use of cardiovascular medication. METHODS: The Serbian cohorts of the Seven Countries Study, Velika Krsna (VK), Zrenjanin (ZR) and Belgrade (BG), were enrolled in 1962-1964 and were followed up for 25 years. The survivors of these cohorts were re-examined in 1987, 1988 and 1989, respectively. This second examination of elderly men aged 65 to 84 years included a questionnaire about current use of cardiovascular medication, risk factors and diseases and a physical examination. All subjects were followed until death or the predefined censor date (10 years after baseline). The Cox proportional hazards model was used to calculate the risk of cardiovascular mortality in the rural cohorts compared to the urban cohort and to adjust for confounding. MAIN OUTCOME MEASURE: Cardiovascular death. RESULTS: A total of 227 men from VK, 184 men from ZR and 287 men from BG were followed for a mean duration of 7.4 years and was complete for all subjects. After exclusion of 13 subjects with missing medication data, the incidences of cardiovascular mortality in VK, ZR, and BG were 60, 74, and 26 per 1,000 person-years, respectively. The prevalence of cardiovascular medication use was 38% in VK, 52% in ZR, and 59% in BG. The greatest difference in use of specific medication was observed for betablockers (0% in VK and ZR, 13% in BG). After adjustment for cardiovascular risk factors, diseases and age, the relative risks (RRs) of cardiovascular mortality were 2.12 [95% CI: 1.44-3.12], and 2.27 [95% CI: 1.56-3.30] in VK, and ZR compared to BG. Additional adjustment for the use of cardiovascular medication increased these RRs to 2.40 [95% CI: 1.61-3.60] and 2.55 [95% CI: 1.72-3.78], respectively. CONCLUSION: The variation in cardiovascular medication use could not explain the excess risk of mortality in the rural Serbian cohorts compared to urban Belgrade.

Aged↗

Preventive drug use in patients with a history of nonfatal myocardial infarction during 12-year follow-up in The Netherlands: a retrospective analysis.

BACKGROUND: Myocardial infarction (MI) is a common cause of death in developed countries. Long-term preventive pharmacotherapy has been shown to decrease mortality and morbidity after MI. Based on a literature search, studies of these therapies to date have estimated the use of monotherapy, whereas many patients are prescribed combination therapy. Thus, assessment of long-term combination drug use after MI is timely. OBJECTIVE: The aim of this study was to assess the use of oral antithrombotics, beta-blockers, angiotensin-converting enzyme (ACE) inhibitors, hydroxymethyl-glutaryl coenzyme A reductase inhibitors ("statins"), and their combinations after MI at discharge and during 12-year follow-up. METHODS: This community-based, retrospective data analysis was conducted at Utrecht University, Utrecht, The Netherlands. Data from patients aged > or =18 years at hospital admission who experienced nonfatal acute MI between 1991 and 2000 and had a duration of follow-up > or =30 days were included in the analysis. Data were retrieved from the Pharmo Record Linkage System database, which links pharmacies' dispensation records to hospitals' discharge records on an individual patient level, allowing the investigator to observe individual patients' medication use over time. Primary outcome measures were the use of preventive medicines (oral antithrombotics, beta-blockers, ACE inhibitors, and statins) at discharge, overall use, and persistence during 12-year follow-up. RESULTS: Of 330,000 patients in the database, 4007 were included in the analysis (2828 men, 1179 women; mean [SD] age, 63.5 [12.5] years). Use at discharge and overall use of oral antithrombotics and statins increased significantly between 1991 and 2000, whereas use of beta-blockers and ACE inhibitors increased mainly in patients discharged in the latter years of the follow-up period. Therapy with any combination of drugs increased strikingly from 1991 to 2000, from 47% to 90%. At 1 year after discharge, 32% of patients had discontinued their first-prescribed combination treatments. At 5 years after discharge, this rate increased to 57%, suggesting a low rate of persistence CONCLUSIONS: Based on the results of this retrospective data analysis, the use of MI-preventive drug treatment at and after discharge increased significantly in this population in The Netherlands during the 1990s. Combination therapy increased strikingly. However, persistence with combination therapy was low.

Adrenergic beta-Antagonists↗

Rate and determinants of 10-year persistence with antihypertensive drugs.

OBJECTIVE: To assess the proportion of patients starting with antihypertensive drug treatment who continued treatment for at least 10 years. DESIGN: A retrospective cohort study. SETTING: The PHARMO record linkage system containing drug dispensing records from community pharmacies and linked hospital discharge records of approximately 950 000 subjects. PARTICIPANTS: Patients who started using antihypertensive drugs (two or more prescriptions) in 1992 and did not receive a prescription for any antihypertensive drug in the 365 days preceding the first prescription. MAIN OUTCOME MEASURE: Persistence with antihypertensive drugs until 10 years. RESULTS: Among a total of 2325 patients who started using antihypertensive drugs, 39% used continuously during the 10 years of follow-up. Approximately 22% temporarily discontinued and restarted treatment, whereas 39% of patients discontinued permanently. Older patients were more persistent than younger patients [20-39 years: odds ratio (OR) 2.08; 95% confidence interval (CI) 1.52-2.84; 40-59 years: (reference), > or = 60 years: OR 0.69; 95% CI 0.54-0.89]. More patients who started with diuretics (reference) and beta blockers (OR 1.15; 95% CI 0.87-1.52) discontinued compared with those who started with dihydropyridine calcium antagonists (OR 0.54; 95% CI 0.34-0.84), and angiotensin-converting enzyme (ACE) inhibitors (OR 0.38; 95% CI 0.27-0.55). Patients who started with combination therapy (OR 0.29; 95% CI 0.14-0.54 compared with diuretics) or patients who were initially treated by a cardiologist (OR 0.82; 95% CI 0.61-0.97) or internist (OR 0.80; 95% CI 0.62-0.98 compared with general practitioners) also showed higher persistence. CONCLUSION: Long-term persistence in daily practice is low compared with persistence observed in randomized clinical trials and should be considered in the choice of a first-line antihypertensive agent.

Adrenergic beta-Antagonists↗

Suboptimal choices and dosing of statins at start of therapy.

AIM: To assess dosing and determinants of the choice of statins among starters of statins. METHODS: Data were obtained from the PHARMO database comprising pharmacy and linked hospital discharge records of approximately 300 000 subjects in the Netherlands. All new users of statins in 1998 were selected. Patient characteristics and drug regimens were compared between starters of different statins. Odds ratios (OR) and 95% confidence intervals (CI) were calculated using polytomous logistic regression modelling, using the start of simvastatin therapy as reference category. RESULTS: In 1998, 1738 patients started using simvastatin (41.1%), pravastatin (23.1%), fluvastatin (11.9%), atorvastatin (22.8%) or cerivastatin (1.0%). Compared with starters with simvastatin [mean dose 1.02 +/- 0.39 defined daily doses (DDDs)], starters with pravastatin (1.27 +/- 0.56 DDDs) and atorvastatin (1.43 +/- 0.59 DDDs) received higher doses (P < 0.001), whereas users of fluvastatin (0.78 +/- 0.37 DDDs) and cerivastatin (0.81 +/- 0.30 DDDs) received lower doses (P < 0.001). Patients already using CYP3A4 inhibitors more frequently received fluvastatin (OR = 1.80; 95% CI 1.11, 2.94), metabolized by non-CYP3A4 pathways, and atorvastatin (OR = 1.62; 95% CI 1.06, 2.47), which is metabolized by CYP3A4, than simvastatin. Statin doses were not adjusted when prescribed to patients using CYP3A4 inhibitors. CONCLUSIONS: Many patients starting statin therapy did not receive a statin of first choice. The coadministration of potentially interacting drugs may have led to a change in statin choice, but not in dosage lowering. These findings suggest that the quality of statin therapy could be improved.

Choice Behavior↗