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The results of the multicentre Study of Heart And Renal Protection(SHARP): Implications for clinical practice in renal disease



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6th October 2011

Chronic kidney disease (CKD) is associated with an increased risk of cardiovascular disease, but little is known about the prevention of cardiovascular disease in patients with CKD.  Meta-analyses of randomised trials conducted chiefly among patients without CKD have shown that statin therapy reduces the risks of major coronary events (myocardial infarction [MI] or death from coronary heart disease [CHD]), ischaemic strokes, and coronary revascularisations by about one fifth for each 1 mmol/L reduction in LDL cholesterol, while producing little effect on haemorrhagic strokes or vascular causes of death other than coronary heart disease.   Among people with estimated glomerular filtration rate (eGFR) above 60 ml/min/1.73m2, in whom the aetiology of cardiovascular disease is typically atherosclerotic, the proportional effects of statin therapy on vascular events appear to be independent of renal function.  But, when eGFR falls below 30 ml/min/1.73m2, a different cardiovascular pathology emerges, with vascular stiffness and calcification, structural heart disease and sympathetic over activity contributing to an increasing risk of cardiac arrhythmia and heart failure.  A key question, therefore, is whether LDL lowering therapy remains effective as renal impairment progresses.

The SHARP (Study of Heart and Renal Protection) trial aimed to assess the safety and efficacy of reducing LDL cholesterol among more than 9000 patients with CKD. In order to achieve an average reduction in LDL cholesterol of about 1 mmol/L without the use of high statin doses (which are associated with an increased risk of myopathy, especially in patients with impaired renal function), a low dose of a statin (simvastatin 20mg daily) was combined with a cholesterol-absorption inhibitor (ezetimibe 10mg daily), and the biochemical efficacy and tolerability of this regimen was first confirmed in the UK-HARP pilot studies. I present the results and the potential implications on patients with CKD and those on dialysis of the SHARP study.

Dr William Majoni is a Nephrologist and Specialist Physician at the RDH. He trained in Nephrology and General internal Medicine in the West Midlands Deanery of the Royal College of Physicians (UK). He took 2 years out of the specialist training programme for a Clinical Research Fellowship at the University of Oxford’s Clinical Trial Service Unit and Epidemiological studies Unit in Oxford. He was involved in the international multicentre Study of Heart and Renal Protection (SHARP) and sits on the steering committee for the study. His research interests include the epidemiology of renal disease and defining risk factors and their management in CKD. He is currently working with Dr Jaqui Hughes and Dr Louise Maple-Brown of the Menzies in a Renal Research Interest Group (RRIG) to set up various research projects in renal disease