The effect of statins on urinary albumin excretion and glomerular filtration rate: results from both a randomized clinical trial and an observational cohort study.

BACKGROUND: Statins improve cardiovascular outcome, but less is known on the renal outcome. We, therefore, studied the relationship between the use of statins and urinary albumin excretion (UAE) and glomerular filtration rate (GFR) in two settings: a randomized controlled trial (RCT) and an observational cohort study, in which patients were included to study the impact of an elevated UAE on renal and cardiovascular prognosis. METHODS: We used data from the Prevention of REnal and Vascular ENd-stage Disease Intervention trial (PREVEND-IT) and the PREVEND cohort study. The PREVEND-IT subjects (788 with a UAE 15-300 mg/day) received pravastatin 40 mg/day vs placebo and/or fosinopril 20 mg/day vs placebo in a 2x2 factorial-RCT design. Of the 3440 cohort subjects, 469 used statins during the 4-year follow-up period. Multivariate-regression adjusted for confounding factors and the propensity score was used to estimate the relation between statin use and UAE and GFR. RESULTS: In the RCT, pravastatin did not change UAE or GFR, neither in fosinopril yes/no subgroups. In the observational cohort, statin use was associated with a rise in UAE (+12.1%), compared with statin non-use (+3.6%, P<0.001). This rise was most pronounced in those on statins prior to the first screening [+24.8% (95% CI: 11.9-39.2)], those using statins>3 years [+18.5% (7.3-30.8)] and those with >1 or >2 defined daily doses (+15.7 and +17.3%, respectively). These differences remained significant after adjustment for relevant variables and propensity score. The rise in UAE could not be attributed to a higher dose or a specific statin. GFR fell in 4 years in both statin users and non-users (4.6+/-13.5 and 2.4+/-11.2, respectively). The fall in GFR between groups was not different after adjustment (P=0.11). CONCLUSIONS: We conclude from the RCT data that statins do not lower UAE in subjects selected because of an elevated UAE instead of hyperlipidaemia. In the observational cohort study, the use of statins similarly was not associated with a fall in UAE; UAE instead increased. Statin treatment was not associated with a significant change in GFR in these subjects with only modestly impaired GFR.     

What predicts progression and regression of urinary albumin excretion in the nondiabetic population?

An increase or decrease in urinary albumin excretion (UAE) is associated with, respectively, a higher or lower risk for renal and cardiovascular disease, independent of widely known cardiovascular risk factors. This study aimed to identify factors that are associated with changes in UAE in the nondiabetic population using data of the Prevention of Renal and Vascular End stage Disease (PREVEND) Study, a community-based prospective cohort study. Data of the 6647 nondiabetic participants who completed the first (1997 through 2001) and second (2001 through 2003) screening were used. Change in UAE was categorized as regression (n = 650), stable (n = 5240), or progression (n = 757) on the basis of change in class during follow-up, with classes being a UAE <15, 15 to 30, 30 to 300, and >300 mg/24 h. With the use of stepwise forward multinomial regression analysis changes in BP, fasting glucose concentration, and start of antihypertensive drugs were found to be the most important modifiable variables associated with the risk for progression and regression (P < 0.01 for likelihood ratio test). The odds ratios to develop regression or progression of UAE during follow-up were 0.64 (95% confidence interval [CI] 0.57 to 0.73) and 1.91 (95% CI 1.72 to 2.12), respectively, per 10-mmHg increase in BP during follow-up, 0.89 (95% CI 0.80 to 0.98) and 1.09 (95% CI 1.01 to 1.17), respectively, per 1-mmol/L increase of fasting glucose levels during follow-up, and 1.57 (95% CI 1.21 to 2.06) and 0.70 (95% CI 0.51 to 0.95), respectively, for start of antihypertensive drugs during follow-up. These associations were independent of baseline BP, glucose, body mass index, estimated GFR, and UAE and changes in high-sensitivity C-reactive protein during follow-up. In conclusion, changes in glucose concentration and BP and start of antihypertensive drugs (angiotensin-converting enzyme inhibitors/angiotensin receptor blockers in >50% of cases) are associated with progression and regression of UAE in the nondiabetic population. Although associations do not necessarily suggest causality, it is hypothesized that in the general population, the most important ways to reduce UAE are by lowering glucose concentration and BP (including start of antihypertensive medication), even in normotensive, nondiabetic individuals.     

Cost-effectiveness of screening for albuminuria with subsequent fosinopril treatment to prevent cardiovascular events: A pharmacoeconomic analysis linked to the prevention of renal and vascular endstage disease (PREVEND) study and the prevention of renal and vascular endstage disease intervention trial (PREVEND IT)

OBJECTIVE: This study estimated the cost-effectiveness,from the Dutch health care perspective, of screening for albuminuria in the general Dutch population to prevent cardiovascular events (CVEs) with subsequent angiotensin-converting enzyme inhibitor treatment, using data from the Prevention of REnal and Vascular ENdstage Disease Intervention Trial (PREVEND IT). METHODS: PREVEND IT was a single-center, double-blind, randomized, placebo-controlled trial with a 2 x 2 factorial design within the larger observational Prevention of REnal and Vascular ENdstage Disease (PREVEND) study. The PREVEND IT study was conducted to assess the effects of fosinopril 20 mg and pravastatin 40 mg on CVEs in subjects with specific inclusion criteria: urinary albumin excretion (UAE) rate in the range from 15 to 300 mg/d, blood pressure <160/100 mm Hg, and plasma cholesterol level <8.0 mmol/L. Cost-effectiveness estimates for the Dutch population were expressed in euros (2002; 1 euro = US 1.01 dollars) as net costs per life-year gained (LYG) in the baseline and sensitivity (stochastic) analyses. RESULTS: Data were assessed for 864 subjects, with a mean (SD) follow-up of 46 (7) months. CVEs occurred in 45 (5.2%) subjects. Subjects who received fosinopril had a 40% lower incidence of CVEs than subjects in the placebo group (3.9% vs 6.5%, respectively; P = NS). The cost-effectiveness of screening for albumnuria was determined to be euro 16,700/LYG for the study population. Stochastic analysis indicated that the probability of the cost-effectiveness being below the suggested Dutch threshold of euro 20,000/LYG was 59% in the baseline analysis. The probability of cost-effectiveness below euro 20,000/LYG would increase to 91% if only subjects with UAE >50 mg/d were treated with fosinopril. Limiting the screening to subjects aged >50 years and >60 years also improved cost-effectiveness. CONCLUSIONS: The results of our study suggest that screening the general Dutch population for albuminuria and subsequently treating those found positive with fosinopril may be cost-effective compared with no screening and adopting the Dutch health care perspective. However, confirmation from larger multicenter trials is needed.     

‘Diabetes is a gift from god’ a qualitative study coping with diabetes distress by Indonesian outpatients

Quality of Life Research - More than two-thirds of patients diagnosed with type 2 diabetes mellitus (T2DM) in Indonesia encounter medical-related problems connected to routine self-management of...     

Baseline albuminuria predicts the efficacy of blood pressure-lowering drugs in preventing cardiovascular events

AIMS

Albuminuria has been proven to be associated with cardiovascular (CV) events in specific patient populations, but also in the general population. This study aimed to investigate whether the efficacy of blood pressure-lowering agents in preventing CV events depends on baseline urinary albumin excretion (UAE) and, if so, whether this holds true for blood pressure-lowering agents in general, or is limited to agents that interfere in the renin–angiotensin system.

METHODS

Data were used from a community-based cohort study and pharmacy dispensing records. Included were subjects with hypertension (systolic blood pressure ≥140 and/or diastolic blood pressure ≥90 mmHg), no cardiovascular disease history, and no previous use of blood pressure-lowering agents.

RESULTS

During study follow-up (7.1 ± 1.6 years), 122 CV events were observed in 1185 subjects included. Start of blood pressure-lowering agents vs. non-use was associated with a difference in absolute CV event risk of 0.7%, 6% and 12.6% for all subjects, those with UAE ≥ 15 mg day⁻¹ and ≥30 mg day⁻¹, respectively. Cox regression analysis showed that the relative risk for CV events after start of blood pressure-lowering agents was significantly dependent (P < 0.05) on baseline UAE; with hazard ratios of 0.87 [95% confidence interval (CI) 0.48, 1.60, P = NS], 0.58 (95% CI 0.36, 0.94, P < 0.05) and 0.37 (95% CI 0.20, 0.68, P < 0.05), for subjects with UAE < 15, ≥15 and ≥30 mg day⁻¹, respectively. Results adjusted for covariates were essentially similar. The use of angiotensin converting enzyme inhibitor/angiotensin-II receptor blocker (ACEi/ARB) treatment tended to be associated with a more favourable CV prognosis when compared with non-ACEi/ARB treatment (difference P = 0.06).

CONCLUSIONS

Our results suggest that the efficacy of blood pressure-lowering agents to prevent CV events is dependent on baseline albuminuria. The higher baseline albuminuria, the more absolute as well as relative risk reduction can be achieved. Our data suggest that this may especially be true for ACEi/ARBs. We caution that this is an observational study, and that these conclusions should therefore be regarded as hypothesis generating, rather than hypothesis testing.

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT

• Albuminuria has been proven to be associated with cardiovascular morbidity and mortality.
• Such an association has been found not only in subjects with diabetes and hypertension, but also in the general population.
• It could therefore be expected that especially subjects with higher albuminuria levels may benefit from blood pressure-lowering agents to improve their cardiovascular outcome.

WHAT THIS STUDY ADDS

• This study indicates that the efficacy of blood pressure-lowering agents to prevent cardiovascular events is dependent of the level of albuminuria before start of such treatment.
• The higher baseline albuminuria, the better the relative and absolute risk reduction for cardiovascular events with blood pressure-lowering drugs.
• The data also suggest a possible better cardiovascular protective effect of renin–angiotensin intervening agents compared with other blood pressure-lowering agents.

     

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.     

Adherence of Pharmacoeconomic Studies to National Guidelines in the Netherlands

Objective: This study examines the adherence of Dutch pharmacoeconomic studies to the national guidelines of conducting a pharmacoeconomic evaluation. Methods: Dutch guidelines for pharmacoeconomic research were issued in 1999. All Dutch pharmacoeconomic studies that were published in English during 2000–2002 were selected for our review. Two reviewers examined each study for relevance and compared each study with the nine methodological guidelines selected. Results: It was found that 29 studies satisfied the inclusion criteria. The societal perspective was taken in 13 out of the 29 studies (45%), an adequate time period of analysis was chosen in 21 (72%), effectiveness was explicitly differentiated from efficacy in 17 (59%), an incremental analysis was performed in 23 (79%), costs, benefits and health gains were discounted in 24 (83%), effectiveness was expressed in LYGs or QALYs in 16 (55%), reference prices were used in 8 (28%), subgroup analysis was presented in 13 (45%) and sensitivity analysis was included in 26 (90%). Conclusions: In this review we found that the adherence of studies to some of the Dutch guidelines for pharmacoeconomic studies is fair. However, major improvements are required with respect to the adoption of the societal perspective, presentation of adequate subgroup analyses and application of reference prices.     

合并有肾病的2型糖尿病患者使用血管紧张素Ⅱ拮抗剂的药物经济学分析：对决策的意义

血管紧张素Ⅱ拮抗剂(血管紧张素Ⅱ受体阻滞剂,ARBs)是一类抗高血压药物,一般认为,其在预防心脏和肾脏衰竭方面作用与ACE抑制剂相当。然而,这两类药物干预肾素-血管紧张素系统的不同阶段。临床试验已证明,ARBs相对于传统治疗方法(非ACE抑制剂)在2型糖尿病患者微蛋白尿到大量蛋白尿的进程、明显的肾病和终末肾病方面的益处。在合并有终末肾病的2型糖尿病患者,需要进行透析和(或)移植,这使得有更多的医疗卫生资源被使用。该论文评价了ARB治疗对有晚期肾病的2型糖尿病患者的经济学依据。RENAAL(Reduction of Endpoint in Noninsulin d…     

Corticosteroid-induced osteoporosis prevention: longitudinal practice patterns in The Netherlands 2001–2005

Summary We investigated prevention trends and predictors for osteoporosis prevention in long term corticosteroid users. The use of bisphosphonates increased from 2001 to 2005. Longer duration of corticosteroid use and DMARD use were predictors for receiving prevention. Females appear reasonably well treated; however, men require more attention. Introduction Previous studies have shown that long-term corticosteroid users are undertreated for osteoporosis prevention. Our aim was to identify prevention trends in long-term corticosteroid users from 2001–2005 in The Netherlands and to identify predictors for bisphosphonate prophylaxis. Methods Pharmacy dispensing data were used from 9 community pharmacies. All oral corticosteroid doses were converted to “prednisolone equivalents”. We then identified long-term (≥90 days) corticosteroid episodes, which required bisphosphonate prophylaxis as per 2002 Dutch guidelines; Multivariate logistic regression was used to identify predictors for receiving prevention. Results We identified 615 different corticosteroid patients requiring prophylaxis. From 2001–2005 the use of bisphosphonates increased from 38% to 54% (p = 0.001). In 2005 females were prescribed more bisphosphonates than males (61% vs. 39%; p = 0.002), or any treatment (72% vs. 45%; p < 0.001). Multivariate analysis showed that longer duration of corticosteroid use and disease-modifying anti-rheumatic drug (DMARD) use were independent predictors of bisphosphonate use. Use of respiratory medication was a negative predictor of bisphosphonate use. Conclusion There has been a significant increase in osteoporosis prophylaxis in a population at high risk for osteoporosis/fractures. In particular, females appear reasonably well treated; however, men are still not receiving prevention to the same degree as women.