Study Of Heart And Renal Protection Research Articles

Prognostic values of left ventricular mass index in chronic kidney disease patients.

Left ventricular hypertrophy is causally implicated in the high risk of death and heart failure (HF) in chronic kidney disease (CKD) patients. Whether the left ventricular mass index (LVMI) adds meaningful predictive power for mortality and de novo HF to simple risk models has not been tested in the CKD population. We investigated this problem in 1352 CKD patients enrolled in the Chronic Renal Insufficiency Cohort (CRIC). LVMI was measured by echocardiography and the risks for death and HF were estimated by the Study of Heart and Renal Protection (SHARP) score, a well-validated risk score in CKD patients. During a median follow-up of 7.7 years, 326 patients died and 208 had de novo HF. The LVMI and the SHARP score and a cross-validated model for HF (CRIC model) were all significantly (P < 0.001) related to the risk of death and HF. LVMI showed a discriminatory power for death (Harrell's C index 66%) inferior to that of the SHARP score (71%) and the same was true for the risk of HF both in the test (LVMI 72%, CRIC model 79%) and in the validation cohort (LVMI 71%, CRIC model 74%). LVMI increased very little the discriminatory (2-3%) and the risk reclassification power (3.0-4.8%) by the SHARP score and the CRIC model for HF for the same outcomes. In CKD, measurement of LVMI solely for the stratification of risk of death and perhaps for the risk of HF does not provide evident prognostic values in this condition.

Apolipoprotein B, Triglyceride-Rich Lipoproteins, and Risk of Cardiovascular Events in Persons with CKD.

Triglyceride-rich lipoproteins may contribute to the high cardiovascular risk of patients with CKD. This study evaluated associations of apo-B and markers of triglyceride-rich lipoproteins with cardiovascular events in people with CKD. Analyses were conducted in 9270 participants with CKD in the Study of Heart and Renal Protection (SHARP): 6245 not on dialysis (mean eGFR 26.5 ml/min per 1.73 m2), and 3025 on dialysis when recruited. Cox regression methods were used to evaluate associations of lipids with incident atherosclerotic and nonatherosclerotic vascular events, adjusting for demographics and clinical characteristics. Hazard ratios (HRs) were calculated per 1 SD higher level for apo-B, HDL cholesterol, LDL cholesterol, triglyceride-rich lipoprotein cholesterol (i.e., total cholesterol minus LDL cholesterol minus HDL cholesterol), non-HDL cholesterol, log triglyceride, and log ratio of triglyceride to HDL cholesterol. During a median follow-up of 4.9 years (interquartile range, 4.0-5.5 years), 1406 participants experienced at least one atherosclerotic vascular event. In multivariable adjusted models, positive associations with atherosclerotic vascular events were observed for apo-B (HR per 1 SD, 1.19; 95% confidence interval, 1.12 to 1.27), triglycerides (1.06; 1.00 to 1.13), the ratio of triglyceride to HDL cholesterol (1.10; 1.03 to 1.18), and triglyceride-rich lipoprotein cholesterol (1.14; 1.05 to 1.25). By contrast, inverse associations with nonatherosclerotic vascular events were observed for each of these lipid markers: apo-B (HR per 1 SD, 0.92; 0.85 to 0.98), triglycerides (0.86; 0.81 to 0.92), the ratio of triglyceride to HDL cholesterol (0.88; 0.82 to 0.94), and triglyceride-rich lipoprotein cholesterol (0.85; 0.77 to 0.94). Higher apo-B, triglycerides, ratio of triglyceride to HDL cholesterol, and triglyceride-rich lipoprotein cholesterol concentrations were associated with increased risk of atherosclerotic vascular events in CKD. Reducing triglyceride-rich lipoproteins using novel therapeutic agents could potentially lower the risk of atherosclerotic cardiovascular disease risk in the CKD population.

Cost-effectiveness of lipid lowering with statins and ezetimibe in chronic kidney disease

Statin-based treatments reduce cardiovascular disease (CVD) risk in patients with non-dialysis chronic kidney disease (CKD), but it is unclear which regimen is the most cost-effective. We used the Study of Heart and Renal Protection (SHARP) CKD-CVD policy model to evaluate the effect of statins and ezetimibe on quality-adjusted life years (QALYs) and health care costs in the United States (US) and the United Kingdom (UK). Net costs below $100,000/QALY (US) or £20,000/QALY (UK) were considered cost-effective. We investigated statin regimens with or without ezetimibe 10 mg. Treatment effects on cardiovascular risk were estimated per 1-mmol/L reduction in low-density lipoprotein (LDL) cholesterol as reported in the Cholesterol Treatment Trialists’ Collaboration meta-analysis, and reductions in LDL cholesterol were estimated for each statin/ezetimibe regimen. In the US, atorvastatin 40 mg ($0.103/day as of January 2019) increased life expectancy by 0.23 to 0.31 QALYs in non-dialysis patients with stages 3B to 5 CKD, at a net cost of $20,300 to $78,200/QALY. Adding ezetimibe 10 mg ($0.203/day) increased life expectancy by an additional 0.05 to 0.07 QALYs, at a net cost of $43,600 to $91,500/QALY. The cost-effectiveness findings and policy implications in the UK were similar. In summary, in patients with non-dialysis-dependent CKD, the evidence suggests that statin/ezetimibe combination therapy is a cost-effective treatment to reduce the risk of CVD.

Protocol for the Study of Heart and Renal Protection-Extended Review: Additional 5-Year Follow-up of the Australian, New Zealand, and Malaysian SHARP Cohort.

Background:There are limited studies on the effects of statins on outcomes in the moderate chronic kidney disease (CKD) population and their trajectory to end-stage kidney disease.Objective:To examine the long-term effects of lipid-lowering therapy on all-cause mortality, cardiovascular morbidity, CKD progression, and socioeconomic well-being in Australian, New Zealand, and Malaysian SHARP (Study of Heart and Renal Protection) trial participants—a randomized controlled trial of a combination of simvastatin and ezetimibe, compared with placebo, for the reduction of cardiovascular events in moderate to severe CKD.Design:Protocol for an extended prospective observational follow-up.Setting:Australian, New Zealand, and Malaysian participating centers in patients with advanced CKD.Patients:All SHARP trial participants alive at the final study visit.Measurements:Primary outcomes were measured by participant self-report and verified by hospital administrative data. In addition, secondary outcomes were measured using a validated study questionnaire of health-related quality of life, a 56-item economic survey.Methods:Participants were followed up with alternating face-to-face visits and telephone calls on a 6-monthly basis until 5 years following their final SHARP Study visit. In addition, there were 6-monthly follow-up telephone calls in between these visits. Data linkage to health registries in Australia, New Zealand, and Malaysia was also performed.Results:The SHARP-Extended Review (SHARP-ER) cohort comprised 1136 SHARP participants with a median of 4.6 years of follow-up. Compared with all SHARP participants who originally participated in the Australian, New Zealand, and Malaysian regions, the SHARP-ER participants were younger (57.2 [48.3-66.4] vs 60.5 [50.3-70.7] years) with a lower proportion of men (61.5% vs 62.8%). There were a lower proportion of participants with hypertension (83.7% vs 85.0%) and diabetes (20.0% vs 23.5%).Limitations:As a long-term follow-up study, the surviving cohort of SHARP-ER is a selected group of the original study participants, which may limit the generalizability of the findings.Conclusion:The SHARP-ER study will contribute important evidence on the long-term outcomes of cholesterol-lowering therapy in patients with advanced CKD with a total of 10 years of follow-up. Novel analyses of the socioeconomic impact of CKD over time will guide resource allocation.Trial Registration:The SHARP trial was registered at ClinicalTrials.gov NCT00125593 and ISRCTN 54137607.

Lipids, inflammation, and chronic kidney disease: a SHARP perspective

Accumulating evidence indicates that inflammation plays a role in the initiation and progression of chronic kidney disease. In the Study of Heart and Renal Protection (SHARP) trial, higher baseline C-reactive protein and higher baseline low-density lipoprotein cholesterol levels were both associated with a higher risk of cardiovascular events, but higher baseline C-reactive protein levels were also associated with a higher risk of nonvascular events. Simvastatin/ezetimibe reduced cardiovascular events independent of baseline C-reactive protein levels. However, this observation does not exclude inflammation as a causal factor for cardiovascular disease development in chronic kidney disease patients.

Impact of CKD on Household Income

IntroductionThe impact of chronic kidney disease (CKD) on income is unclear. We sought to determine whether CKD severity, serious adverse events, and CKD progression affected household income.MethodsAnalyses were undertaken in a prospective cohort of adults with moderate-to-severe CKD in the Study of Heart and Renal Protection (SHARP), with household income information available at baseline screening and study end. Logistic regressions, adjusted for sociodemographic characteristics, smoking, and prior diseases at baseline, estimated associations during the 5-year follow-up, among (i) baseline CKD severity, (ii) incident nonfatal serious adverse events (vascular or cancer), and (iii) CKD treatment modality (predialysis, dialysis, or transplanted) at study end and the outcome “fall into relative poverty.” This was defined as household income <50% of country median income.ResultsA total of 2914 SHARP participants from 14 countries were included in the main analysis. Of these, 933 (32%) were in relative poverty at screening; of the remaining 1981, 436 (22%) fell into relative poverty by study end. Compared with participants with stage 3 CKD at baseline, the odds of falling into poverty were 51% higher for those with stage 4 (odds ratio [OR]: 1.51; 95% confidence interval [CI]: 1.09–2.10), 66% higher for those with stage 5 (OR: 1.66; 95% CI: 1.11–2.47), and 78% higher for those on dialysis at baseline (OR: 1.78, 95% CI: 1.22–2.60). Participants with kidney transplant at study end had approximately half the risk of those on dialysis or those with CKD stages 3 to 5.ConclusionMore advanced CKD is associated with increased odds of falling into poverty. Kidney transplantation may have a role in reducing this risk.

Lowering LDL cholesterol reduces cardiovascular risk independently of presence of inflammation

Markers of inflammation, including plasma C-reactive protein (CRP), are associated with an increased risk of cardiovascular disease, and it has been suggested that this association is causal. However, the relationship between inflammation and cardiovascular disease has not been extensively studied in patients with chronic kidney disease. To evaluate this, we used data from the Study of Heart and Renal Protection (SHARP) to assess associations between circulating CRP and LDL cholesterol levels and the risk of vascular and non-vascular outcomes. Major vascular events were defined as nonfatal myocardial infarction, cardiac death, stroke or arterial revascularization, with an expanded outcome of vascular events of any type. Higher baseline CRP was associated with an increased risk of major vascular events (hazard ratio per 3x increase 1.28; 95% confidence interval 1.19-1.38). Higher baseline LDL cholesterol was also associated with an increased risk of major vascular events (hazard ratio per 0.6 mmol/L higher LDL cholesterol; 1.14, 1.06-1.22). Higher baseline CRP was associated with an increased risk of a range of non-vascular events (1.16, 1.12-1.21), but there was a weak inverse association between baseline LDL cholesterol and non-vascular events (0.96, 0.92-0.99). The efficacy of lowering LDL cholesterol with simvastatin/ezetimibe on major vascular events, in the randomized comparison, was similar irrespective of CRP concentration at baseline. Thus, decisions to offer statin-based therapy to patients with chronic kidney disease should continue to be guided by their absolute risk of atherosclerotic events. Estimation of such risk may include plasma biomarkers of inflammation, but there is no evidence that the relative beneficial effects of reducing LDL cholesterol depends on plasma CRP concentration.

A policy model of cardiovascular disease in moderate-to-advanced chronic kidney disease

ObjectiveTo present a long-term policy model of cardiovascular disease (CVD) in moderate-to-advanced chronic kidney disease (CKD).MethodsA Markov model with transitions between CKD stages (3B, 4, 5, on dialysis, with kidney...

Effect on non-vascular outcomes of lowering LDL cholesterol in patients with chronic kidney disease: results from the Study of Heart and Renal Protection

BackgroundReducing LDL cholesterol (LDL-C) with statin-based therapy reduces the risk of major atherosclerotic events among patients with chronic kidney disease (CKD), with no evidence of an excess risk of cancer or death from any non-vascular cause. However, non-randomized data have suggested that statin therapy may have effects (both adverse and beneficial) on particular non-vascular conditions that do not cause death.MethodsThe Study of Heart and Renal Protection (SHARP) randomized patients with CKD to simvastatin 20 mg plus ezetimibe 10 mg (simvastatin/ezetimibe) daily versus matching placebo. Participants were followed up at least 6 monthly and all post-randomization serious adverse events (SAEs) were recorded. This supplementary analysis reports the effects of treatment on non-vascular SAEs, overall, by system of disease, by baseline characteristics, and by duration of follow-up.ResultsDuring a median of 4.9 years follow-up, similar numbers of participants in the two groups experienced at least one non-vascular SAE (3551 [76.4%] simvastatin/ezetimibe vs 3537 [76.6%] placebo; risk ratio [RR] 0.99, 95% confidence interval [CI] 0.95–1.04). There was no good evidence of any significant effect of simvastatin/ezetimibe on SAEs attributed to any particular nonvascular disease system (of 43 comparisons, only 3 yielded an uncorrected p value < 0.05, of which the smallest was p = 0.02). The relative risk of any nonvascular SAE did not vary significantly among particular prognostic subgroups or by duration of follow-up.ConclusionsIn the SHARP trial, allocation to simvastatin/ezetimibe combination therapy was not associated with any significant non-vascular hazard.Trials registrationSHARP was retrospectively registered after the first participant was enrolled in 2003 at ISRCTN (ISRCTN54137607 on 31 January 2005: http://www.isrctn.com/ISRCTN54137607) and ClinicalTrials.gov (NCT00125593 on 29 July 2005: https://clinicaltrials.gov/ct2/show/NCT00125593).

Evidence for Reverse Causality in the Association Between Blood Pressure and Cardiovascular Risk in Patients With Chronic Kidney Disease.

URL: http://www.clinicaltrials.gov. Unique identifier: NCT00125593.

Predictors of atherosclerotic events in patients on haemodialysis: post hoc analyses from the AURORA study.

Patients on haemodialysis (HD) are at high risk for cardiovascular events, but heart failure and sudden death are more common than atherosclerotic events. The A Study to Evaluate the Use of Rosuvastatinin in Subjects on Regular Hemodialysis: An Assessment of Survival and Cardiovascular Events (AURORA) trial was designed to assess the effect of rosuvastatin on myocardial infarction and death from any cardiac cause in 2773 HD patients. We studied predictors of the atherosclerotic cardiovascular events in AURORA. We readjudicated all deaths and presumed myocardial infarctions according to the criteria used in the Study of Heart and Renal Protection (SHARP); these were specifically developed to separate atherosclerotic from non-atherosclerotic cardiovascular events. The readjudicated atherosclerotic end point included the first event of the following: non-fatal myocardial infarction, fatal coronary heart disease, non-fatal and fatal non-haemorrhagic stroke, coronary revascularization procedures and death from ischaemic limb disease. Stepwise Cox regression analysis was used to identify the predictors of such events. During a mean follow-up of 3.2 years, 506 patients experienced the new composite atherosclerotic outcome. Age, male sex, prevalent diabetes, prior cardiovascular disease, weekly dialysis duration, baseline albumin [hazard ratio (HR) 0.96; 95% confidence interval (CI) 0.94-0.99 per g/L increase], high-sensitivity C-reactive protein (HR 1.13; 95% CI 1.04-1.22 per mg/L increase) and oxidized low-density lipoprotein (LDL) cholesterol (HR 1.09; 95% CI 1.03-1.17 per 10 U/L increase) were selected as significant predictors in the model. Neither LDL cholesterol nor allocation to placebo/rosuvastatin therapy predicted the outcome. Even with the use of strict criteria for end point definition, non-traditional risk factors, but not lipid disturbances, predicted atherosclerotic events in HD patients.

Use of Causal Diagrams to Inform the Design and Interpretation of Observational Studies: An Example from the Study of Heart and Renal Protection (SHARP).

Observational studies often seek to estimate the causal relevance of an exposure to an outcome of interest. However, many possible biases can arise when estimating such relationships, in particular bias because of confounding. To control for confounding properly, careful consideration of the nature of the assumed relationships between the exposure, the outcome, and other characteristics is required. Causal diagrams provide a simple graphic means of displaying such relationships, describing the assumptions made, and allowing for the identification of a set of characteristics that should be taken into account (i.e., adjusted for) in any analysis. Furthermore, causal diagrams can be used to identify other possible sources of bias (such as selection bias), which if understood from the outset, can inform the planning of appropriate analyses. In this article, we review the basic theory of causal diagrams and describe some of the methods available to identify which characteristics need to be taken into account when estimating the total effect of an exposure on an outcome. In doing so, we review the concept of collider bias and show how it is inappropriate to adjust for characteristics that may be influenced, directly or indirectly, by both the exposure and the outcome of interest. A motivating example is taken from the Study of Heart and Renal Protection, in which the relevance of smoking to progression to ESRD is considered.

Smoking and Adverse Outcomes in Patients With CKD: The Study of Heart and Renal Protection (SHARP).

BackgroundThe absolute and relative importance of smoking to vascular and nonvascular outcomes in people with chronic kidney disease (CKD), as well its relevance to kidney disease progression, is uncertain.Study DesignObservational study.Setting & Participants9,270 participants with CKD enrolled in SHARP.PredictorBaseline smoking status (current, former, and never).OutcomesVascular events, site-specific cancer, ESRD, rate of change in estimated glomerular filtration rate (eGFR), and cause-specific mortality.ResultsAt baseline, 1,243 (13%) participants were current smokers (median consumption, 10 cigarettes/day); 3,272 (35%), former smokers; and 4,755 (51%), never smokers. Median follow-up was 4.9 years. Vascular event rates were 36% higher for current than never smokers (2,317 events; relative risk [RR], 1.36; 95% CI, 1.19-1.55), reflecting increases in both atherosclerotic (RR, 1.49; 95% CI, 1.26-1.76) and nonatherosclerotic (RR, 1.25; 95% CI, 1.05-1.50) events. Cancer was 37% higher among current smokers (632 events; RR, 1.37; 95% CI, 1.07-1.76), with the biggest RRs for lung (RR, 9.31; 95% CI, 4.37-19.83) and upper aerodigestive tract (RR, 4.87; 95% CI, 2.10-11.32) cancers. For 6,245 patients not receiving dialysis at baseline, ESRD incidence did not differ significantly between current and never smokers (2,141 events; RR, 1.02; 95% CI, 0.89-1.17), nor did estimated rate of change in eGFR (current smokers, −1.77 ± 0.14 [SE]; never smokers, −1.70 ± 0.07 mL/min/1.73 m2 per year). All-cause mortality was 48% higher among current smokers (2,257 events; RR, 1.48; 95% CI, 1.30-1.70), with significant increases in vascular (RR, 1.35; 95% CI, 1.07-1.69) and nonvascular (RR, 1.60; 95% CI, 1.34-1.91) causes of death, especially cancer (RR, 2.32; 95% CI, 1.58-3.40) and respiratory (RR, 2.25; 95% CI, 1.51-3.35) mortality.LimitationsSmoking status not assessed during follow-up.ConclusionsIn this study of patients with CKD, smoking significantly increased the risks for vascular and nonvascular morbidity and mortality, but was not associated with kidney disease progression. The associations with vascular and neoplastic disease are in keeping with those observed in the general population and are likely modifiable by cessation.

Considerations in Applying the Results of Randomized Controlled Clinical Trials to the Care of Older Adults With Kidney Disease in the Clinical Setting: The SHARP Trial

The Study of Heart and Renal Protection (SHARP) found that treatment with ezetemibe and low-dose simvastatin reduced the incidence of major atherosclerotic events in patients with kidney disease. Due to the paucity of evidence-based interventions that lower cardiovascular morbidity in this high-risk population, the SHARP trial will likely have a large impact on clinical practice. However, applying the results of clinical trials conducted in select populations to the care of individual patients in real-world settings can be fraught with difficulty. This is especially true when caring for older adults with complex comorbidity and limited life expectancy. These patients are often excluded from clinical trials, frequently have competing health priorities, and may be less likely to benefit and more likely to be harmed by medications. We discuss key considerations in applying the results of the SHARP trial to the care of older adults with CKD in real-world clinical settings using guiding principles set forth by the American Geriatrics Society's Expert Panel on the Care of Older Adults with Multimorbidity. Using this schema, we emphasize the importance of evaluating trial results in the unique context of each patient's goals, values, priorities, and circumstances.

Cost-effectiveness of Simvastatin plus Ezetimibe for Cardiovascular Prevention in CKD: Results of the Study of Heart and Renal Protection (SHARP)

BackgroundSimvastatin, 20 mg, plus ezetimibe, 10 mg, daily (simvastatin plus ezetimibe) reduced major atherosclerotic events in patients with moderate to severe chronic kidney disease (CKD) in the Study of Heart and Renal Protection (SHARP), but its cost-effectiveness is unknown.Study DesignCost-effectiveness of simvastatin plus ezetimibe in SHARP, a randomized controlled trial.Setting & Population9,270 patients with CKD randomly assigned to simvastatin plus ezetimibe versus placebo; participants in categories by 5-year cardiovascular risk (low, <10%; medium, 10%-<20%; or high, ≥20%) and CKD stage (3, 4, 5 not on dialysis, or on dialysis therapy).Model, Perspective, & TimelineAssessment during SHARP follow-up from the UK perspective; long-term projections.InterventionSimvastatin plus ezetimibe (2015 UK £1.19 per day) during 4.9 years’ median follow-up in SHARP; scenario analyses with high-intensity statin regimens (2015 UK £0.05-£1.06 per day).OutcomesAdditional health care costs per major atherosclerotic event avoided and per quality-adjusted life-year (QALY) gained.ResultsIn SHARP, the proportional reductions per 1 mmol/L of low-density lipoprotein (LDL) cholesterol reduction with simvastatin plus ezetimibe in all major atherosclerotic events of 20% (95% CI, 6%-32%) and in the costs of vascular hospital episodes of 17% (95% CI, 4%-28%) were similar across participant categories by cardiovascular risk and CKD stage. The 5-year reduction in major atherosclerotic events per 1,000 participants ranged from 10 in low-risk to 58 in high-risk patients and from 28 in CKD stage 3 to 36 in patients on dialysis therapy. The net cost per major atherosclerotic event avoided with simvastatin plus ezetimibe compared to no LDL-lowering regimen ranged from £157,060 in patients at low risk to £15,230 in those at high risk (£30,500-£39,600 per QALY); and from £47,280 in CKD stage 3 to £28,180 in patients on dialysis therapy (£13,000-£43,300 per QALY). In scenario analyses, generic high-intensity statin regimens were estimated to yield similar benefits at substantially lower cost.LimitationsHigh-intensity statin-alone regimens were not studied in SHARP.ConclusionsSimvastatin plus ezetimibe prevented atherosclerotic events in SHARP, but other less costly statin regimens are likely to be more cost-effective for reducing cardiovascular risk in CKD.

Impact of Educational Attainment on Health Outcomes in Moderate to Severe CKD

BackgroundThe inverse association between educational attainment and mortality is well established, but its relevance to vascular events and renal progression in a population with chronic kidney disease (CKD) is less clear. This study aims to determine the association between highest educational attainment and risk of vascular events, cause-specific mortality, and CKD progression.Study DesignProspective epidemiologic analysis among participants in the Study of Heart and Renal Protection (SHARP), a randomized controlled trial.Setting & Participants9,270 adults with moderate to severe CKD (6,245 not receiving dialysis at baseline) and no history of myocardial infarction or coronary revascularization recruited in Europe, North America, Asia, Australia, and New Zealand.PredictorHighest educational attainment measured at study entry using 6 levels that ranged from “no formal education” to “tertiary education.”OutcomesAny vascular event (any fatal or nonfatal cardiac, cerebrovascular, or peripheral vascular event), cause-specific mortality, and CKD progression during 4.9 years’ median follow-up.ResultsThere was a significant trend (P < 0.001) toward increased vascular risk with decreasing levels of education. Participants with no formal education were at a 46% higher risk of vascular events (relative risk [RR], 1.46; 95% CI, 1.14-1.86) compared with participants with tertiary education. The trend for mortality across education levels was also significant (P < 0.001): all-cause mortality was twice as high among those with no formal education compared with tertiary-educated individuals (RR, 2.05; 95% CI, 1.62-2.58), and significant increases were seen for both vascular (RR, 1.84; 95% CI, 1.21-2.81) and nonvascular (RR, 2.15; 95% CI, 1.60-2.89) deaths. Lifestyle factors and prior disease explain most of the excess mortality risk. Among 6,245 participants not receiving dialysis at baseline, education level was not significantly associated with progression to end-stage renal disease or doubling of creatinine level (P for trend = 0.4).LimitationsNo data for employment or health insurance coverage.ConclusionsLower educational attainment is associated with increased risk of adverse health outcomes in individuals with CKD.

What is the impact of chronic kidney disease stage and cardiovascular disease on the annual cost of hospital care in moderate-to-severe kidney disease?

BackgroundReliable estimates of the impacts of chronic kidney disease (CKD) stage, with and without cardiovascular disease, on hospital costs are needed to inform health policy.MethodsThe Study of Heart and Renal Protection (SHARP) randomized trial prospectively collected information on kidney disease progression, serious adverse events and hospital care use in a cohort of patients with moderate-to-severe CKD. In a secondary analysis of SHARP data, the impact of participants’ CKD stage, non-fatal cardiovascular events and deaths on annual hospital costs (i.e. all hospital admissions, routine dialysis treatments and recorded outpatient/day-case attendances in United Kingdom 2011 prices) were estimated using linear regression.Results7,246 SHARP patients (2,498 on dialysis at baseline) from Europe, North America, and Australasia contributed 28,261 years of data. CKD patients without diabetes or vascular disease incurred annual hospital care costs ranging from £403 (95% confidence interval: 345-462) in CKD stages 1-3B to £525 (449-602) in CKD stage 5 (not on dialysis). Patients in receipt of maintenance dialysis incurred annual hospital costs of £18,986 (18,620-19,352) in the year of initiation and £23,326 (23,231-23,421) annually thereafter. Patients with a functioning kidney transplant incurred £24,602 (24,027-25,178) in hospital care costs in the year of transplantation and £1,148 (978-1,318) annually thereafter. Non-fatal major vascular events increased annual costs in the year of the event by £6,133 (5,608-6,658) for patients on dialysis and by £4,350 (3,819-4,880) for patients not on dialysis, and were associated with increased costs, though to a lesser extent, in subsequent years.ConclusionsRenal replacement therapy and major vascular events are the main contributors to the high hospital care costs in moderate-to-severe CKD. These estimates of hospital costs can be used to inform health policy in moderate-to-severe CKD.Electronic supplementary materialThe online version of this article (doi:10.1186/s12882-015-0054-0) contains supplementary material, which is available to authorized users.

Critical Appraisal of the SHARP Trial: The Results May Be Dull

PurposeThe goal of this commentary was to provide a critical analysis of the SHARP (Study of Heart and Renal Protection) trial. Published in 2011, this study has been used by clinicians to justify the prescribing of statins (3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors) ±ezetimibe in patients with chronic kidney disease. MethodsWe conducted a critical appraisal of the SHARP trial and associated documents (ie, US Food and Drug Administration review, SHARP protocol). We also examined background reviews and studies conducted before the SHARP trial to provide additional context and background. FindingsOur analysis provides clinicians with important criticisms of the SHARP trial, which suggest questionable clinical benefit to lipid-lowering therapy in patients with chronic kidney disease. ImplicationsOur hope is that clinicians limit the broad prescription of statins (±ezetimibe) in all patients with chronic kidney disease (both dialysis and nondialysis) unless there is a valid reason for statin therapy (eg, existing cardiovascular disease).

KHA-CARI commentary on the KDIGO Clinical Practice Guideline for Lipid Management in Chronic Kidney Disease.

Due to the markedly accelerated risks of cardiovascular disease for people who have chronic kidney disease (CKD), lipid-lowering treatment represents a potentially effective intervention to reduce cardiovascular events, including death from cardiovascular disease. However, existing randomized trials have been inconsistent about whether statin therapy is beneficial for all patients with CKD, particularly those who are treated with dialysis, while data for recipients of a kidney transplant and children with CKD are sparse. Given the extensive trial data that have become available over recent years and in particular, information from the Study of Heart and Renal Protection (SHARP) trial of simvastatin/ezetimibe which involved more than 9000 adults with advanced kidney disease, lipid management is a highly relevant guideline for development by the Kidney Disease Improving Global Outcomes (KDIGO) group. The KDIGO ‘Clinical Practice Guideline for Lipid Management in Chronic Kidney Disease’ was published in November 2013 and makes 13 recommendations. In this commentary, we consider the recommendations made in the KDIGO guideline with particular reference to the New Zealand and Australian context. Overall, the KDIGO guideline recommendations are suitable for Australasian clinical practice.

The effect of lowering LDL cholesterol on vascular access patency: post hoc analysis of the Study of Heart and Renal Protection.

Reducing LDL cholesterol (LDL-C) with statin-based therapy reduces the risk of major atherosclerotic events among patients with CKD, including dialysis patients, but the effect of lowering LDL-C on vascular access patency is unclear. The Study of Heart and Renal Protection (SHARP) randomized patients with CKD to 20 mg simvastatin plus 10 mg ezetimibe daily versus matching placebo. This study aimed to explore the effects of treatment on vascular access occlusive events, defined as any access revision procedure, access thrombosis, removal of an old dialysis access, or formation of new permanent dialysis access. Among 2353 SHARP participants who had functioning vascular access at randomization, allocation to simvastatin plus ezetimibe resulted in a 13% proportional reduction in vascular access occlusive events (355 [29.7%] for simvastatin/ezetimibe versus 388 [33.5%] for placebo; risk ratio [RR], 0.87; 95% confidence interval [95% CI], 0.75 to 1.00; P=0.05). There was no evidence that the effects of treatment differed for any of the separate components of this outcome. To test the hypothesis raised by SHARP, comparable analyses were performed using the AURORA (A Study to Evaluate the Use of Rosuvastatin in Subjects on Regular Hemodialysis: An Assessment of Survival and Cardiovascular Events) trial cohort. AURORA did not provide independent confirmation (vascular access occlusive events: 352 [28.9%] for rosuvastatin versus 337 [27.6%] for placebo; RR, 1.06, 95% CI, 0.91 to 1.23; P=0.44). After combining the two trials, the overall effect of reducing LDL-C with a statin-based regimen on vascular access occlusive events was not statistically significant (707 [29.3%] with any LDL-C-lowering therapy versus 725 [30.5%] with placebo; RR, 0.95, 95% CI, 0.85 to 1.05; P=0.29). Exploratory analyses from SHARP suggest that lowering LDL-C with statin-based therapy may improve vascular access patency, but there was no evidence of benefit in AURORA. Taken together, the available evidence suggests that any benefits of lowering LDL-C on vascular access patency are likely to be modest.