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- Baigent, Colin, et al.
(author)
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The effects of lowering LDL cholesterol with simvastatin plus ezetimibe in patients with chronic kidney disease (Study of Heart and Renal Protection) : a randomised placebo-controlled trial
- 2011
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In: The Lancet. - 0140-6736 .- 1474-547X. ; 377:9784, s. 2181-2192
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Journal article (peer-reviewed)abstract
- Background Lowering LDL cholesterol with statin regimens reduces the risk of myocardial infarction, ischaemic stroke, and the need for coronary revascularisation in people without kidney disease, but its effects in people with moderate-to-severe kidney disease are uncertain. The SHARP trial aimed to assess the efficacy and safety of the combination of simvastatin plus ezetimibe in such patients. Methods This randomised double-blind trial included 9270 patients with chronic kidney disease (3023 on dialysis and 6247 not) with no known history of myocardial infarction or coronary revascularisation. Patients were randomly assigned to simvastatin 20 mg plus ezetimibe 10 mg daily versus matching placebo. The key prespecified outcome was first major atherosclerotic event (non-fatal myocardial infarction or coronary death, non-haemorrhagic stroke, or any arterial revascularisation procedure). All analyses were by intention to treat. This trial is registered at ClinicalTrials.gov, NCT00125593, and I SRCTN54137607. Findings 4650 patients were assigned to receive simvastatin plus ezetimibe and 4620 to placebo. Allocation to simvastatin plus ezetimibe yielded an average LDL cholesterol difference of 0.85 mmol/L (SE 0.02; with about two-thirds compliance) during a median follow-up of 4.9 years and produced a 17% proportional reduction in major atherosclerotic events (526 [11.3%] simvastatin plus ezetimibe vs 619 [13.4%] placebo; rate ratio [RR] 0.83, 95% CI 0.74-0.94; log-rank p=0.0021). Non-significantly fewer patients allocated to simvastatin plus ezetimibe had a non-fatal myocardial infarction or died from coronary heart disease (213 [4.6%] vs 230 [5.0%]; RR 0.92,95% CI 0.76-1.11; p=0.37) and there were significant reductions in non-haemorrhagic stroke (131 [2.8%] vs 174 [3.8%]; RR 0.75,95% CI 0.60-0.94; p=0.01) and arterial revascularisation procedures (284 [6.1%] vs 352 [7.6%]; RR 0.79, 95% CI 0.68-0.93; p=0.0036). After weighting for subgroup-specific reductions in LDL cholesterol, there was no good evidence that the proportional effects on major atherosclerotic events differed from the summary rate ratio in any subgroup examined, and, in particular, they were similar in patients on dialysis and those who were not. The excess risk of myopathy was only two per 10 000 patients per year of treatment with this combination (9 [0.2%] vs 5 [0.1%]). There was no evidence of excess risks of hepatitis (21 [0.5%] vs 18 [0.4%]), gallstones (106 [2.3%] vs 106 [2.3%]), or cancer (438 [9.4%] vs 439 [9.5%], p=0.89) and there was no significant excess of death from any non-vascular cause (668 [14.4%] vs 612 [13.2%], p=0.13). Interpretation Reduction of LDL cholesterol with simvastatin 20 mg plus ezetimibe 10 mg daily safely reduced the incidence of major atherosclerotic events in a wide range of patients with advanced chronic kidney disease.
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- Mafham, Marion M, et al.
(author)
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Prognostic utility of estimated albumin excretion rate in chronic kidney disease : results from the Study of Heart and Renal Protection
- 2018
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In: Nephrology, Dialysis and Transplantation. - : Oxford University Press. - 0931-0509 .- 1460-2385. ; 33:2, s. 257-264
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Journal article (peer-reviewed)abstract
- Background: Estimated albumin excretion rate (eAER) provides a better estimate of 24-h albuminuria than albumin:creatinine ratio (ACR). However, whether eAER is superior to ACR in predicting end-stage renal disease (ESRD), vascular events (VEs) or death is uncertain.Methods: The prognostic utility of ACR and eAER (estimated from ACR, sex, age and race) to predict mortality, ESRD and VEs was compared using Cox proportional hazards regression among 5552 participants with chronic kidney disease in the Study of Heart and Renal Protection, who were not on dialysis at baseline.Results: During a median follow-up of 4.8 years, 1959 participants developed ESRD, 1204 had a VE and 1130 died (641 from a non-vascular, 369 from a vascular and 120 from an unknown cause). After adjustment for age, sex and eGFR, both ACR and eAER were strongly and similarly associated with ESRD risk. The average relative risk (RR) per 10-fold higher level was 2.70 (95% confidence interval 2.45-2.98) for ACR and 2.67 (2.43-2.94) for eAER. Neither ACR nor eAER provided any additional prognostic information for ESRD risk over and above the other. For VEs, there were modest positive associations between both ACR and eAER and risk [adjusted RR per 10-fold higher level 1.37 (1.22-1.53) for ACR and 1.36 (1.22-1.52) for eAER]. Again, neither measure added prognostic information over and above the other. Similar results were observed when ACR and eAER were related to vascular mortality [RR per 10-fold higher level: 1.64 (1.33-2.03) and 1.62 (1.32-2.00), respectively] or to non-vascular mortality [1.53 (1.31-1.79) and 1.50 (1.29-1.76), respectively].Conclusions: In this study, eAER did not improve risk prediction of ESRD, VEs or mortality.
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