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Biomedical subjects

Dick de Zeeuw

Publications and source records attributed to Dick de Zeeuw.

At least 37 records · Page 2Linked to original sources
PubMed2006

Pharmacoeconomics of angiotensin II antagonists in type 2 diabetic patients with nephropathy: implications for decision making.

Angiotensin II receptor antagonists (angiotensin II receptor blockers; ARBs) are a class of antihypertensive drugs that are generally considered comparable to ACE inhibitors in the prevention of heart and kidney failure. However, these two classes of agents do interfere in different stages of the renin-angiotensin system. In patients with type 2 diabetes mellitus, advantages for ARBs over conventional (non-ACE inhibitor) therapy on progression from micro- to macroalbuminuria and overt nephropathy and end-stage renal disease have been shown in clinical trials. In patients with type 2 diabetes and end-stage renal disease, the need for dialysis and/or transplantation results in the use of major healthcare resources. This paper reviews the available economic evidence on treatment with ARBs in type 2 diabetic patients with advanced renal disease.Within-trial analytic and Markov model economic evaluations of the RENAAL (Reduction of Endpoint in Non-insulin dependent diabetes mellitus with Angiotensin II Antagonist Losartan), IDNT (Irbesartan Diabetic Nephropathy Trial) and IRMA (IRbesartan in type 2 diabetes with MicroAlbuminuria)-2 studies suggest that treatment with ARBs in patients with type 2 diabetes with overt or incipient nephropathy confers health gains and net cost savings compared with conventional (non-ACE inhibitor) therapy. For reimbursement and reference pricing decisions, there is a need for a head-to-head comparison of an ACE inhibitor with ARBs to model all possible costs and effects of ACE inhibitors and ARBs. This will result in a proper pharmacoeconomic outcome, where both types of drugs can be compared for healthcare decisions.

Angiotensin II Type 1 Receptor Blockers↗
PubMed2005

Physicians' attitudes towards treatment guidelines: differences between teaching and nonteaching hospitals.

OBJECTIVE: To investigate whether physicians' attitudes towards treatment guidelines for primary and secondary care differ between teaching and nonteaching hospitals shortly before and 4 years after the guidelines' introduction. METHODS: Possible barriers and facilitators of joint treatment guidelines were obtained by self-administered questionnaires twice during the study period. Questionnaires were distributed among all internists and cardiologists in the Groningen region of The Netherlands. RESULTS: Physicians from teaching and nonteaching hospitals differed in attitude regarding the content and usefulness of the guidelines. Physicians from nonteaching hospitals more often believed that the guidelines are too restrictive (64% vs. 18%) and too rigid to apply to individual patients (14% vs. 6%) and that they oversimplify medical practice (79% vs. 35%). Physicians from teaching hospitals more often agreed that good recommendations for first-choice drugs had been made (76% vs. 50%) and that these guidelines are a convenient source of advice (94% vs. 57%), can facilitate communication with general practitioners (94% vs. 71%), and can improve the quality of pharmacotherapeutic care (88% vs. 43%). Four years later, a larger proportion of physicians from both hospital settings had a negative attitude towards the usefulness of the guidelines, but the difference in attitude between teaching and nonteaching hospitals remained the same. CONCLUSION: Physicians from nonteaching hospitals were less positive about the usefulness of joint treatment guidelines than physicians from teaching hospitals were. Results from studies on the implementation of guidelines in teaching hospitals can therefore not be transferred to nonteaching settings.

Attitude of Health Personnel↗
PubMed2005

Uptake of angiotensin II receptor blockers in the treatment of hypertension.

OBJECTIVE: To examine trends in prescribing of angiotensin II receptor blockers (ARBs) as initial and second-line treatment of hypertension. METHODS: We performed a cohort study in the Integrated Primary Care Information database, a general practice research database in The Netherlands. We included hypertensive patients who were newly treated with antihypertensive drugs between 1996 and 1999. Initial treatment was defined as the first prescribed antihypertensive drug after diagnosis of hypertension. As second-line treatment, we considered prescriptions of a second antihypertensive drug class, either as switch or addition. We used logistic regression and Cox proportional hazard analysis to estimate time trends in use of ARBs as initial or second-line treatment. RESULTS: In total, 8% of the 3,102 newly treated hypertensive patients received ARBs as initial treatment. Initial ARB use increased significantly from 4% to 10% during the period 1996-1999, whereas calcium channel blocker and angiotensin-converting enzyme inhibitor (ACE-I) use decreased. ARBs were used as second-line treatment in less than 4% of 2,544 patients who were initially treated with an antihypertensive drug other than an ARB: 2% switched to an ARB (mostly from ACE-Is) and 1% received ARBs as add-on treatment. Diuretics and beta-blockers were used five to ten times more often as add-on treatment than ARBs. CONCLUSION: ARBs achieved a position in the treatment of hypertension as initial rather than second-line therapy.

Adolescent↗
PubMed2005

Importance of baseline distribution of proteinuria in renal outcomes trials: lessons from the reduction of endpoints in NIDDM with the angiotensin II antagonist losartan (RENAAL) study.

A key issue in the analysis of outcome trials is the adjustment for baseline covariates that influence the primary outcome. Imbalance of an important covariate between treatment groups at baseline is of considerable concern if one treatment group is favored over another with respect to the hypothesis testing outcome. With the use of the Reduction of Endpoints in NIDDM with the Angiotensin II Antagonist Losartan (RENAAL) study database as an example, the influence of baseline proteinuria on the primary composite endpoint, ESRD, and ESRD or death after adjusting for baseline proteinuria as a continuous covariate was examined. Increasing baseline proteinuria was associated with increased risk for renal events, confirming that proteinuria is an important covariate for renal outcomes. When the randomization was stratified according proteinuria <2000 mg/g or >/=2000 mg/g, within the higher proteinuria stratum (>/=2000 mg/g), patients in the losartan group had a higher baseline mean proteinuria value. When the imbalance was adjusted, an increase in the magnitude and the significance of the risk reduction with losartan for each outcome was observed. No apparent interaction between treatment effect and baseline proteinuria was found, and there was no heterogeneity in the treatment response in patients with different baseline proteinuria levels. After proteinuria was adjusted as a continuous variable, greater treatment effects were observed in the RENAAL study. This effect was due solely to the imbalance in baseline proteinuria. Considering the importance of proteinuria as a risk factor, adjustment for baseline proteinuria as a continuous covariate should be prespecified in the design and analysis of clinical trials involving renal outcomes, even when patients are stratified on the basis of level of proteinuria.

Adult↗
PubMed2005

Microalbuminuria and C-reactive protein: similar messengers of cardiovascular risk?

C-reactive protein (CRP) and urinary albumin excretion are both determinants of cardiovascular risk. The first is closely related to systemic and vascular low-grade inflammation, the latter is considered to be a marker of endothelial dysfunction. Because of these properties, one might presume them to be closely interrelated. In this article, we review the available evidence concerning the relationships of CRP and urinary albumin excretion, with each other and with other cardiovascular risk markers and factors. Should they be considered as dependent or independent risk markers, and which risk markers might be present in the cardiovascular risk estimation formula of the near future? The reasons that this formula might or should include CRP and urinary albumin excretion, rather than diabetes mellitus and the metabolic syndrome, are discussed.

Albuminuria↗
PubMed2005

Rationale--Trial to Reduce Cardiovascular Events with Aranesp Therapy (TREAT): evolving the management of cardiovascular risk in patients with chronic kidney disease.

BACKGROUND: Patients with chronic kidney disease (CKD) have a high burden of mortality and cardiovascular morbidity. Additional strategies to modulate cardiovascular risk in this population are needed. Data suggest that anemia is a potent and potentially modifiable risk factor for cardiovascular disease in patients with CKD, but these data remain unsubstantiated by any randomized controlled trial (RCT). Furthermore, the clinical practice guidelines for anemia management in patients with CKD are based on limited data. The need for new RCTs to address critical knowledge deficits, particularly with regard to the impact of anemia therapy on cardiovascular disease and survival, is recognized within the guidelines and independent comprehensive reviews of the existing published trial data. STUDY DESIGN: The Trial to Reduce Cardiovascular Events with Aranesp (Amgen Inc, Thousand Oaks, Calif) (darbepoetin alfa) Therapy (TREAT) is a 4000-patient, multicenter, double-blind RCT, designed to determine the impact of anemia therapy with darbepoetin alfa on mortality and nonfatal cardiovascular events in patients with CKD and type 2 diabetes mellitus. Subjects will be randomized in a 1:1 manner to either darbepoetin alfa therapy to a target hemoglobin (Hb) of 13 g/dL or control, consisting of placebo for Hb > or =9 g/dL or darbepoetin alfa for Hb <9 g/dL until Hb is again Hb > or =9 g/dL. TREAT is event-driven and has a composite primary end point comprising time to mortality and nonfatal cardiovascular events, including myocardial infarction, myocardial ischemia, stroke, and heart failure. TREAT will provide data that are critical to evolution of the management of cardiovascular risk in this high-risk population.

Anemia↗
PubMed2005

Beneficial effects of add-on hydrochlorothiazide in rats with myocardial infarction optimally treated with quinapril.

BACKGROUND: The antihypertensive and renoprotective effects of ACE inhibitor (ACEi) therapy are enhanced by inducing a negative sodium balance. Whether this strategy also improves outcome of chronic ACEi treatment after myocardial infarction (MI) is unknown. Therefore, we investigated whether hydrochlorothiazide (HCTZ) or dietary sodium restriction further improves survival in ACEi-treated rats with MI. METHODS: MI was induced by coronary ligation. After 2 weeks rats were randomised to quinapril (QUI), HCTZ added to quinapril (QUI+HCTZ), or low sodium diet added to quinapril (QUI+LS). Survival was monitored for 62 weeks, after which left ventricular (LV) pressures were measured and blood for neurohumoral characterisation was collected. A separate group of rats, subjected to the same procedure, was evaluated after 35 weeks. RESULTS: After 62 weeks, mortality was comparable in all groups. However, survival was improved by HCTZ until 35 weeks. This effect on survival was paralleled by decreased proteinuria and LV end-diastolic pressures in QUI+HCTZ rats at 35, but not 62 weeks. Plasma renin activity was significantly decreased in QUI+HCTZ rats at 35 weeks. Contrary to HCTZ, LS added to QUI caused no benefit. CONCLUSIONS: Adding HCTZ, but not LS, to quinapril improved survival, neurohumoral status, and proteinuria during the early chronic phase of experimental post-MI LV dysfunction. Since no adverse effects were observed, HCTZ may safely be used to improve ACEi therapy.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed2005

The angiotensin II receptor antagonist telmisartan reduces urinary albumin excretion in patients with isolated systolic hypertension: results of a randomized, double-blind, placebo-controlled trial.

OBJECTIVE: To examine the effect of telmisartan or hydrochlorothiazide on the control of urinary albumin excretion (UAE) in patients with isolated systolic hypertension (ISH) unselected for albuminuria in a pre-planned substudy of a large, multicentre, double-blind, placebo-controlled, randomized study. METHODS: The Angiotensin II Receptor Antagonist Micardis in Isolated Systolic hypertension (ARAMIS) study compared the antihypertensive efficacy after 6 weeks of once-daily fixed doses of telmisartan 20, 40 or 80 mg versus hydrochlorothiazide 12.5 mg or placebo in patients (n = 1039, aged 35-84 years) with ISH (seated blood pressure 150-179/< 90 mmHg). The prospective substudy analysed UAE using spot morning samples. RESULTS: Urinary albumin (> 2.2-901.6 mg/l) was detected at baseline in 614 out of 918 patients who were included in the substudy analysis. In the telmisartan group (n = 354, all doses combined), a median reduction in UAE from a baseline of 14.1% [95% confidence interval (CI) 7.3, 21.8] was observed versus 1.1% (95% CI -13.5 to 16.0) and 2.7% (95% CI -0.9 to 19.9) in the hydrochlorothiazide (n = 140) and placebo (n = 120) groups, respectively. The difference between telmisartan and hydrochlorothiazide was significant (P = 0.017). Reductions in UAE with telmisartan were observed in patients with baseline normoalbuminuria, microalbuminuria or macroalbuminuria. Telmisartan and hydrochlorothiazide produced comparable reductions in systolic blood pressure in these patients. CONCLUSION: In patients with ISH unselected for baseline albuminuria, telmisartan 20-80 mg after 6 weeks' treatment afforded significantly greater lowering of UAE than hydrochlorothiazide 12.5 mg, irrespective of the baseline UAE, and despite comparable reductions in systolic blood pressure with both drugs.

Adult↗
PubMed2005

The association between atherosclerotic risk factors and renal function in the general population.

BACKGROUND: Generalized atherosclerosis is increasingly recognized as an important cause of end-stage renal disease (ESRD). We questioned to what extent atherosclerotic risk factors determine renal function in the general population. METHODS: We used baseline data of the Prevention of Renal and Vascular End-Stage Disease (PREVEND) Study. A total of 8592 subjects, aged 28 to 75 years old, visited the outpatient clinic for blood pressure and anthropometric measurements, fasting blood sampling, and delivery of two 24-hour urine collections for creatinine clearance and albuminuria calculations. Design-based multivariate linear regression was used to estimate renal function. RESULTS: In a multivariate model, male gender and body mass index (BMI) were associated with a higher renal function, while increasing diastolic blood pressure, serum triglycerides, use of antihypertensive or lipid-lowering medication were associated with a lower renal function. Age, systolic blood pressure, and plasma glucose showed an inverse U-shaped relationship with renal function. Cholesterol/high-density lipoprotein (HDL) ratio, smoking, and antidiabetic medication did not contribute to explain renal function. The atherosclerotic risk factors were related to renal function independently of albuminuria or C-reactive protein (CRP). Albuminuria and CRP itself were also related to renal function. Following gender and age, BMI, urinary albumin excretion (UAE), and plasma glucose had the strongest relation with renal function. CONCLUSION: We conclude that differences in renal function in the general population are (partly) explained by various atherosclerotic risk factors. Some risk factors are associated with elevated filtration, some with an impaired filtration, and others with both a higher and a lower renal function.

Adult↗
PubMed2005

Irbesartan is projected to be cost and life saving in a Spanish setting for treatment of patients with type 2 diabetes, hypertension, and microalbuminuria.

OBJECTIVES: The purpose of this study was to project the cumulative incidence of end-stage renal disease (ESRD), life expectancy, and costs in a Spanish setting of treating patients with diabetes, hypertension, and microalbuminuria with either standard hypertension treatment alone or standard hypertension treatment plus irbesartan 300 mg daily. METHODS: A peer-reviewed, published Markov model that simulated progression from microalbuminuria to nephropathy, doubling of serum creatinine, ESRD, and all-cause mortality in patients with hypertension, type 2 diabetes, and microalbuminuria was adapted to a Spanish setting. Two strategies were compared: (1) irbesartan versus (2) standard hypertension care with comparable blood pressure control; both began in diabetic hypertensive subjects with microalbuminuria. Cumulative incidence of ESRD, costs, and life expectancy were projected for a hypothetical cohort of 1000 subjects. Future costs and life expectancy were discounted at 3% yearly. A 25-year time horizon and third party payer perspective were used. RESULTS: When compared to standard blood pressure control, irbesartan was projected to reduce the cumulative incidence of ESRD from (mean +/- standard deviation) 24 +/- 1% to 9 +/- 2%, save 11,082 +/- 2,996 euro, and add 1.40 +/- 0.27 life years per treated patient. The superiority of irbesartan over standard care was robust under a wide range of plausible assumptions. CONCLUSION: Treating patients with hypertension, microalbuminuria, and type 2 diabetes with irbesartan was projected to reduce the incidence of ESRD, extend life, and reduce costs.

Albuminuria↗
PubMed2005

A report with consensus statements of the International Society of Nephrology 2004 Consensus Workshop on Prevention of Progression of Renal Disease, Hong Kong, June 29, 2004.

This report summarizes the discussions of the International Society of Nephrology (ISN) 2004 Consensus Workshop on Prevention of Progression of Renal Disease, which was held in Hong Kong on June 29, 2004. Three key areas were discussed during the workshop: (1) screening for chronic kidney disease; (2) evaluation and estimating progression of chronic kidney disease; and (3) measures to prevent the progression of chronic kidney disease. Fifteen consensus statements were made in these three areas, as endorsed by the participants of the workshop. The ISN can make use of and take reference to these statements in formulating its policy for tackling chronic kidney disease, a disease with significant global impact.

Hong Kong↗
PubMed2005

The validity of screening based on spot morning urine samples to detect subjects with microalbuminuria in the general population.

BACKGROUND: No study has yet investigated the validity of prescreening by albumin measurements in a spot morning urine sample to identify in the general population subjects with microalbuminuria. We therefore tested the diagnostic performance of urinary albumin concentration (UAC) and albumin-creatinine ratio (ACR), measured in a spot morning urine sample, in predicting a urinary albumin excretion (UAE) > or =30 mg in subsequent 24-hour urines (microalbuminuria). METHODS: Subjects (2527) participating in the PREVEND study, a representative sample from the general population, collected a spot morning urine sample and, on average, 77 days later, two 24-hour urine collections. RESULTS: The ROC curve of UAC in predicting microalbuminuria has an area-under-the-curve of 0.92 with a discriminator value of 11.2 mg/L. Using this cut-off value for UAC, sensitivity in predicting microalbuminuria is 85.0%, and specificity 85.0%. For ACR these values are, respectively: area-under-the-curve 0.93, discriminator value 9.9 mg/g, sensitivity 87.6%, and specificity 87.5%. Sensitivity for UAC in predicting microalbuminuria does not differ significantly from the sensitivity for ACR, whereas the difference between the specificities of UAC and ACR reaches statistical significance, but is numerically very small. In various subgroups characterized by differences in urinary creatinine excretion, the area-under-the-ROC curve, sensitivity, as well as specificity, do not increase relevantly compared to the results in the overall study population. This holds true for ACR as well as UAC. CONCLUSION: The diagnostic performance of measuring UAC in a spot morning urine sample in predicting microalbuminuria in subsequent 24-hour urine collections is satisfactory, and, moreover, comparable to that of measuring ACR. In order to keep the burden and costs involved in population screening for microalbuminuria as low as possible, we therefore propose prescreening by measuring UAC in a spot morning urine sample. Those subjects with a UAC above a certain predefined level (e.g., 11 mg/L) should be asked to collect timed urine samples.

Adult↗
PubMed2005

Renoprotection with and without blood pressure reduction.

BACKGROUND: AT1-receptor blockade dose dependently lowers blood pressure (BP) and albuminuria. Reduction of BP and albuminuria are independent treatment targets for renoprotection, but whether this requires similar dose titration is unknown. METHODS: We tested this in two studies designed to find the optimal antialbuminuric dose of losartan in type 1 diabetic (DM, N= 50) and nondiabetic renal patients (ND, N= 12). After baseline, treatment followed with losartan 50, 100, and 150 mg/day, each dose for eight (DM) or six weeks (ND). At the end of each period, albuminuria (24-hour samples) and mean arterial pressure (MAP) were measured. Patients were divided into "good" and "poor" BP responders (BP+, BP-) according to BP response above or below group median. RESULTS: Baseline MAP in the BP- groups was 102 (97, 104) mm Hg in DM (median, 95% CI) and 91 (80, 108) mm Hg in ND. The top of the dose response for BP (obtained at losartan 100 mg) in the BP- groups was -2 (-4, 3) mm Hg in DM and -1 (-6, 2) mm Hg in ND, versus -15 (-18, -12) mm Hg and -16 (-26, -18) mm Hg in BP+ groups (both P < 0.05). Albuminuria was reduced dose dependently both in BP- and BP+: with 100 mg, the reduction in albuminuria in DM BP- was -32% (-49, 13) versus -45% (-60, -38) in DM BP+ and -45% (-70,-7) versus -25% (-58, -6) in ND BP- and BP+ (all P > 0.05). Moreover, in patients in whom BP fell below the recommended treatment target of 130/80 mm Hg (13 in DM and 10 in ND), albuminuria was progressively reduced, with further increasing the dose of losartan in most patients. CONCLUSION: Absence of BP response to losartan does not preclude a reduction in albuminuria, and optimal reduction of albuminuria may require titration beyond the predefined BP target.

Adult↗
PubMed2005

Prevention of chronic kidney and vascular disease: toward global health equity--the Bellagio 2004 Declaration.

Chronic kidney disease (CKD) not only reflects target organ injury in systemic vascular disease in the general population and in association with diabetes, hypertension, and smoking, but it is recognized as one of the major risk factors in the pathogenesis and outcome of cardiovascular disease. Recent surveys have revealed that the prevalence of CKD, particularly the hidden mild form (mildly elevated levels of serum creatinine or urinary albumin excretion), is surprisingly high in the general population. In recent years, the global epidemic of type 2 diabetes has led to an alarming increase in the number of patients with CKD. Most patients with CKD (over 50 million individuals worldwide) succumb to cardiovascular events, while each year over 1 million develop end-stage renal failure, which requires costly treatment and in many countries of the world, unaffordable renal replacement therapy by chronic dialysis or renal transplantation. Alarmed by the immense challenge to human morbidity and the economic burden of CKD and ensuing systemic cardiovascular disease, the International Society of Nephrology convened a multidisciplinary group of expert physicians and public health leaders from around the world to develop strategies to delay and avert this bleak future by effective prevention of CKD based on awareness, early detection, and effective treatment.

Cardiovascular Diseases↗
PubMed2005

The kidney, a cardiovascular risk marker, and a new target for therapy.

Both reduced filtration power and increased excretion of albumin in the urine are powerful markers for renal and cardiovascular progressive function loss. These risk markers indicate the risk above and beyond the conventional existing risk markers/factors. The risk is substantial, because both reduced filtration and microalbuminuria are highly prevalent in the general population, matching in prevalence with the most well-known risk factor, hypertension. Therapeutic interventions to preserve renal and cardiovascular function, such as with angiotensin-converting enzyme inhibitors and angiotensin II receptor antagonists, are highly effective, particularly in those patients that have reduced filtration power. In addition, short-term reduction of albuminuria that follows the renin-angiotensin-aldosterone-system intervention appears to be predictive of long-term cardiovascular and renal protection. In conclusion, estimated glomerular filtration rate as well as albumin excretion in the urine are powerful predictors for cardiovascular and renal outcome and should be used as such. Intervention and prevention could be aimed at not only at reducing conventional risk markers, but also at reducing albuminuria.

Albuminuria↗