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.............................................................................................. Recommendations for lipid-lowering therapy in patients with HF and valvular diseases are shown below.

9.8 Chronic kidney disease

CKD is defined as abnormalities of kidney structure or function, present for >3 months, with implications for health. CKD is classified on the basis of the cause, GFR category, and category of albuminuria.488 In the adult population, decreasing GFR is associated with increased CVD risk, independent of other CV risk factors.489492 There is an increased risk of both atherosclerotic vascular disease and structural heart disease.492 Patients with CKD and established CVD have a much higher mortality rate compared with patients with CVD and normal renal function.493 Therefore, patients with CKD are considered to be at high (stage 3 CKD) or very-high risk (stage 45 CKD or on dialysis) of CVD, and there is no need to use risk estimation models in these patients.

9.8.1 Lipoprotein profile in chronic kidney disease In the initial stages of CKD, TG levels are specifically elevated and HDL-C levels are lowered. LDL subclasses display a shift to an excess of small dense LDL particles. Studies suggest that the kidney has a role in Lp(a) catabolism and that Lp(a) levels are increased in association with kidney disease. Such acquired abnormalities can be reversed by kidney transplantation or remission of nephrosis.

9.8.2 Evidence for risk reduction through statin-based therapy in patients with chronic kidney disease In the Die Deutsche Diabetes Dialyse Studie (4D) trial, which involved 1200 patients with diabetes on haemodialysis, atorvastatin had no significant effect on risk of CVD.220 Similar results were obtained in the AURORA (A study to evaluate the Use of Rosuvastatin in subjects On Regular haemodialysis: an Assessment of survival and cardiovascular events) trial, which involved 2776 patients on haemodialysis.221 In the SHARP study,222 simvastatin and ezetimibe combination therapy reduced the risk for major atherosclerotic events (coronary death, MI, non-haemorrhagic stroke, or any revascularization) compared with placebo in persons with CKD stage 3A5. The trial did not have sufficient power to separately assess the effects on the primary outcome in dialysis and non-dialysis patients. Although statin-based therapy is clearly effective in mild-to-moderate CKD, a major controversy that remained after the publication of the 4D, AURORA, and SHARP studies was whether statin therapy is effective in more advanced CKD, particularly dialysis patients. By combining data from the three CKD trials with other trials in the existing database, the CTT investigators found that, even after adjusting for the smaller LDL-C reductions achieved among patients with more advanced CKD and for differences in outcome definitions between dialysis trials, there was a trend towards smaller relative reductions per mmol/L reduction in LDL-C in major atherosclerotic events as estimated GFR (eGFR) declines (with little evidence of benefit among dialysis patients).214 This diminution in relative risk reduction as GFR declines implies that, at least in non-dialysis patients, more intensive LDL-lowering regimens are required to achieve the same benefit.

9.8.3 Safety of lipid management in patients with chronic kidney disease Safety issues and dose adjustments are important in advanced stages of CKD (stages 35), as adverse events are commonly dose-related and due to increased blood concentrations of compounds. Although it has been suggested that preference should be given to regimens and doses that have been shown to be beneficial in RCTs conducted specifically in such patients,494 the CTT meta-analysis makes clear that the goal—as in patients without CKD—should be to achieve the largest possible absolute reduction in LDL-C safely. Although there were no specific safety concerns raised by the 4D, AURORA, or SHARP trials, statins metabolized via CYP3A4 may result in adverse effects due to drugdrug interactions and caution is required. Based on the evidence for lipid management in patients with CKD, the Kidney Disease: Improving Global Outcomes (KDIGO) organization has developed an updated clinical practice guideline for lipid management in CKD.494 In line with this, but with a focus on those patients at high or very-high risk for developing CVD, recommendations are summarized below.

Recommendations for the treatment of dyslipidaemias in chronic heart failure or valvular heart diseases

Recommendations Classa Levelb

Initiation of lipid-lowering therapy is not recommended in patients with HF in the absence of other indications for their use.466,470 III A Initiation of lipid-lowering treatment in patients with aortic valvular stenosis without CAD to slow progression of aortic valve stenosis in the absence of other indications for their use is not recommended.266,479481 III A

CAD = coronary artery disease; HF = heart failure. aClass of recommendation. bLevel of evidence.

Recommendations for lipid management in patients with moderate-to-severe (Kidney Disease Outcomes Quality Initiative stages 35) chronic kidney disease

Recommendations Classa Levelb

It is recommended that patients with Kidney Disease Outcomes Quality Initiative stage 35c CKD are considered to be at high or very-high risk of ASCVD.489493 I A The use of statins or statin/ezetimibe combination is recommended in patients with non-dialysis-dependent stage 35 CKD.214,222,495,496 I A In patients already on statins, ezetimibe, or a statin/ezetimibe combination at the time of dialysis initiation, continuation of these drugs should be considered, particularly in patients with ASCVD. IIa C In patients with dialysis-dependent CKD who are free of ASCVD, commencement of statin therapy is not recommended.220,221 III A

ASCVD = atherosclerotic cardiovascular disease; CKD = chronic kidney disease; eGFR = estimated glomerular filtration rate. aClass of recommendation. bLevel of evidence. cDefined as eGFR < 60ml/min/1.73m2 on two measurements more than 3 months apart. Downloaded from academic.oup.com/eurheartj/article/41/1/111/5556353 by guest on 07 October 2026