Lipid lowering in patients with chronic kidney disease: a SHARP turn in the wrong direction?

The question whether lipid-lowering treatment is associated with a decrease in cardiovascular morbidity and mortality in patients with chronic kidney disease has been disputed for a while, with recent trials in patients on haemodialysis failing to show benefit. Recently, the long-awaited results of the SHARP (Study of Heart And Renal Protection) trial were published. This randomized trial compared the effects of either simvastatin 20 mg plus ezetimibe 10 mg daily or placebo on the occurrence of a first major vascular event in 9720 patients with chronic kidney disease. There was a 17% relative risk reduction but no benefit on survival. We address our concerns regarding the conclusions drawn from this trial. The trial has a major design flaw by comparing the effects of two different lipid-lowering drugs with placebo. Although the SHARP trial showed that lipid lowering may be beneficial for patients with chronic kidney disease, the clinically as well as economically important question remains unanswered as to whether it was statin therapy and/or ezetimibe that mediated this effect. A great opportunity to investigate superiority, equipoise, or potential inferiority of ezetimibe compared to statins was missed.

Prevention of diabetes and reduction in major cardiovascular events in studies of subjects with prediabetes: meta-analysis of randomised controlled clinical trials

Background: Impaired glucose tolerance (IGT) and impaired fasting glucose (IFG) are pre-diabetic states, treatment of which may prevent or delay the onset of overt diabetes and thus potentially reduce major cardiovascular (CV) events. We therefore sought to determine whether interventions (including diet, exercise and pharmacological therapy), altered all-cause and cardiovascular related mortality in such subjects. Methods: We performed a meta-analysis of prospective, randomised controlled trials (RCTs) that were identified in the medical literature and databases. Trials were eligible for inclusion if they reported all-cause mortality rates (at a minimum), recruited approximately 100 patients and had a minimum follow-up of one year. Interventions were divided into pharmacological and non-pharmacological. Results: Ten RCTs that enrolled 23,152 patients met the above entry criteria. Trials ran for an average of 3.75 years. Diabetes was delayed or prevented by these interventions vs control (risk ratio 0.83, 95%CI 0.80–0.86). Non-drug approaches ( n = 3495) were superior to drug-based approaches ( n = 20,872) in diabetes prevention (0.52, 0.46–0.58 vs 0.70, 0.58–0.85, P < 0.05). There was no difference in risk of all-cause mortality in the intervention versus control group (0.96, 0.84–1.10) and no difference in CV death (1.04, 0.61–1.78). There was a non-significant trend towards reduction in fatal and non-fatal myocardial infarction (0.59, 0.23–1.50). Fatal and non-fatal stroke was borderline reduced (0.76, 0.58–0.99) with intervention versus control. Conclusions: Despite interventions being mostly successful in retarding progression to overt diabetes, this did not result in reductions in all-cause or cardiovascular mortality, or myocardial infarction, with the possible exception of stroke.