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- Baigent, Colin, et al.
(författare)
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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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Ingår i: The Lancet. - 0140-6736 .- 1474-547X. ; 377:9784, s. 2181-2192
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Tidskriftsartikel (refereegranskat)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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| 3. |
- Kramer, Anneke, et al.
(författare)
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Association between pre-transplant dialysis modality and patient and graft survival after kidney transplantation
- 2012
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Ingår i: Nephrology Dialysis Transplantation. - : Oxford University Press (OUP). - 1460-2385 .- 0931-0509. ; 27:12, s. 4473-4480
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Tidskriftsartikel (refereegranskat)abstract
- Background. Previous studies have found inconsistent associations between pre-transplant dialysis modality and subsequent post-transplant survival. We aimed to examine this relationship using the instrumental variable method and to compare the results with standard Cox regression. Methods. We included 29 088 patients (age > 20 years) from 16 European national or regional renal registries who received a first kidney transplant between 1 January 1999 and 31 December 2008 and were on dialysis before transplantation for a period between 90 days and 10 years. Standard multivariable Cox regression examined the association of individually assigned pre-transplant dialysis modality with post-transplant patient and graft survival. To decrease confounding-by-indication through unmeasured factors, we applied the instrumental variable method that used the case-mix adjusted centre percentage of peritoneal dialysis (PD) as predictor variable. Results. Standard analyses adjusted for age, sex, primary renal disease, donor type, duration of dialysis, year of transplantation and country suggested that PD before transplantation was associated with better patient [hazard ratio, HR (95% CI) = 0.83 (0.76-0.91)] and graft survival (HR (95% CI) 0.90 (0.84-0.96)) when compared with haemodialysis (HD). In contrast, the instrumental variable analysis showed that a 10% increase in the case-mix adjusted centre percentage of patients on PD was neither associated with post-transplant patient survival [HR (95% CI = 1.00 (0.97-1.04)] nor with graft survival [HR (95% CI) = 1.01 (0.98-1.04)]. Conclusions. The instrumental variable method failed to confirm the associations found in standard Cox regression between pre-transplant dialysis modality and patient and graft survival after transplantation. The lack of association in instrumental variable analysis may be due to better control of residual confounding.
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