Table 4.

Completed large studies on lipid modification in patients with CKDa

StudyDrugDesignPatient CharacteristicsNo. of PatientsFollow-UpHR (95% CI) of Outcomes
Randomized trials
    4D (12)Atorvastatin 20 mg/dRandomized, double-blind, placebo-controlled, investigator-initiatedType 2 diabetes on HD <2 yr with LDL cholesterol 80 to 190 mg/dl and TG <1000 mg/dl12554 yr0.92 (0.77 to 1.10) for primary end point (cardiac death, stroke, or nonfatal MI); 0.82 (0.68 to 0.99) for secondary end point (total death, all cardiac or cerebrovascular events)
    CARE (11)Pravastatin 40 mg/dPost hoc subgroup analysis of investigator-initiated, randomized, double-blind, placebo-controlled trialPrevious MI with TC <240 mg/dl; subgroup analysis of patients with CrCl ≤75 ml/min but plasma creatinine <1.5 times upper limit of normal171159 mo0.72 (0.55 to 0.95) for primary end point (coronary death or nonfatal MI); 0.72 (0.59 to 0.88) for major coronary events; 0.81 (0.61 to 1.08) for total death; 0.62 (0.39 to 1.00) for stroke
    PPP (10)Pravastatin 40 mg/dPost hoc subgroup analysis of pooled data from three randomized, double-blind, placebo-controlled trials (WOSCOPS, CARE, and LIPID)CKD stage 3; WOSCOPS studied primary prevention of high-risk patients with high TC; CARE and LIPID studied secondary prevention with average TC44915 yr0.77 (0.68 to 0.86) for primary end point (MI, coronary death, or coronary revascularization); 0.79 (0.71 to 0.88) for extended end point (primary end point or stroke); 0.86 (0.74 to 1.00) for total death
    VA-HIT (9)Gemfibrozil 1200 mg/dPost hoc subgroup analysis of randomized, double-blind, placebo-controlled trialEstablished coronary disease with HDL cholesterol ≤40 mg/dl, LDL cholesterol ≤140 mg/dl, and TG ≤300 mg/dl; subgroup analysis of patients with CrCl ≤75 ml/min but plasma creatinine <2.0 mg/dl10465.3 yr0.73 (0.56 to 0.96) for primary end point (coronary death or nonfatal MI); 0.74 (0.58 to 0.95) for coronary death, nonfatal MI, or stroke; 0.85 (0.66 to 1.10) for coronary revascularization; 1.03 (0.78 to 1.35) for total death
    HPS (7)Simvastatin 40 mg/dPrespecified subgroup analysis of randomized, double-blind, placebo-controlled trialCoronary or other occlusive arterial disease or diabetes; plasma creatinine 110 to 200 μmol/L for women and 130 to 200 μmol/L for men13295 yr0.78 (significantly different) for first major vascular event (including coronary events, stroke, and revascularization)
    LIPS (8)Fluvastatin 40 mg twice dailyPost hoc subgroup analysis of randomized, placebo-controlled trialAfter first successful percutaneous coronary intervention; CrCl <56 ml/min but plasma creatinine <1.8 mg/dl3103.8 yr15% experienced cardiac death, MI, or re-intervention unrelated to restenosis versus 29% in placebo group (P = 0.004)
    ASCOT-LLA (6)Atorvastatin 10 mg/dPrespecified subgroup analysis of randomized, double-blind, placebo-controlled trialHypertension with three additional CVD risk factors, TC <250 mg/dl and plasma creatinine <200 μmol/L65173.3 yr0.61 (0.44 to 0.84) for primary end point (nonfatal MI or fatal CHD)
    Holdaas et al. (5)FluvastatinPost hoc subgroup analysis of pooled data from 30 randomized, double-blind trialsCrCl <50 ml/min15636 wk to 6 yr0.83 (0.63 to 1.09) for cardiac death, nonfatal MI, or coronary interventions; 0.59 (0.40 to 0.87) for cardiac death or MI; 0.78 (0.57 to 1.06) for total death; 0.87 (0.60 to 1.26) for noncardiac death
    Ferramosca et al. (4)SevelamerRandomized trial comparing sevelamer or calcium acetatePrevalent HD1081 yrCoronary artery score progressed significantly in calcium-treated patients but not in sevelamer-treated patients
Observational studies
    USRDS (107)Statins, fibratesRetrospective analysis of existing databaseAll PD patients and 20% random sample of all HD patients in United States3716 (statin = 362; fibrate = 78)1996 to mid-1998Statin: 0.68 (0.53 to 0.86) for total death; 0.63 (0.44 to 0.91) for CVD deathfibrate: 1.29 (0.85 to 1.95) for total death; 1.41 (0.79 to 2.51) for CVD death
    DOPPS (140)StatinsRetrospective analysis of existing databasePrevalent HD7365 (statins = 11.8%)Through mid-20010.69 (0.60 to 0.79) for total death; 0.78 (0.62 to 0.98) for cardiac events; 0.77 (0.61 to 0.97) for cardiac death; 0.56 (0.46 to 0.69) for noncardiac death
    Winkelmayer et al. (141)StatinsRetrospective analysis of existing databasePost-MI dialysis patients aged ≥65 yr494 (statin = 96)1 yr0.97 (0.65 to 1.45) for total death
    GENDIAN (142)StatinsProspectivePrevalent HD with type 2 diabetes irrespective of lipid levels445 (statin = 122)4 yr0.58 (0.34 to 0.99) for total death
  • a CHD, coronary heart disease; CI, confidence interval; CrCl, creatinine clearance; CVD, cardiovascular disease; HD, hemodialysis; HR, hazard ratio; PD, peritoneal dialysis; 4D, Die Deutsche Diabetes-Dialyse Study; CARE, Cholesterol and Recurrent Events Trial; PPP, Pravastatin Pooling Project; VA-HIT, Veterans Affairs HDL Intervention Trial; HPS, Heart Projection Study; LIPS, Lescol Intervention Prevention Study; ASCOT-LLA, Anglo-Scandinavian Cardiac Outcomes Trial: Lipid-Lowering; USRDS, United States Renal Data System; DOPPS, Dialysis Outcomes and Practice Patterns Study; GENDIAN, Genetic and Clinical Predictors of Morbidity, Mortality, and Diabetic Nephropathy with ESRD Renal Disease in Diabetes Mellitus Type 2.