Statins cause a significant reduction in the risk of all-cause and cardiovascular mortality in CKD patients who are not requiring dialysis

Navaneethan SD, Pansini F, Perkovic V, Manno C, Pellegrini F, Johnson DW, Craig JC, Strippoli GFM

Published Online:

July 8, 2009

Patients with chronic kidney disease (CKD) are at very high risk of heart disease. Statins have been shown to decrease cholesterol levels and mortality in the general population. The aim of this review was to analyse if a similar effect could be shown in patients with non-dialysis dependent CKD. This review identified 26 completed studies (25,017 patients). Statins decreased all-cause mortality and cardiovascular mortality along with lowering lipid levels to an extent which is similar to that found in the general population. Statins also reduce protein excretion in urine but the impact of this on the risk of needing renal replacement therapy needs to be studied further. Statins were not found to have serious adverse effects in this group of people.

Abstract (click to read)

Background:

Dyslipidaemia occurs frequently in chronic kidney disease (CKD) patients and contributes both to cardiovascular disease and worsening renal function. Statins are widely used in non-dialysis dependent CKD patients (pre-dialysis) even though evidence favouring their use is lacking.

Objectives:

To evaluate the benefits and harms of statins in CKD patients who were not receiving renal replacement therapy.

Search strategy:

We searched MEDLINE, EMBASE, CENTRAL (in The Cochrane Library), and hand-searched reference lists of textbooks, articles and scientific proceedings.

Selection criteria:

Randomised controlled trials (RCTs) and quasi-RCTs comparing statins with placebo, no treatment or other statins in adult pre-dialysis CKD patients.

Data collection and analysis:

Two authors independently assessed study quality and extracted data. Results were expressed as mean difference (MD) for continuous outcomes (lipids, creatinine clearance and proteinuria) and risk ratio (RR) for dichotomous outcomes (all-cause mortality, cardiovascular mortality, fatal and non-fatal cardiovascular events, elevated liver enzymes, rhabdomyolysis and withdrawal rates) with 95% confidence intervals (CI).

Main results:

Twenty six studies (25,017 participants) comparing statins with placebo were identified. Total cholesterol decreased significantly with statins (18 studies, 1677 patients: MD -41.48 mg/dL, 95% CI -49.97 to -33.99). Similarly, LDL cholesterol decreased significantly with statins (16 studies, 1605 patients: MD -42.38 mg/dL, 95% CI -50.71 to -34.05). Statins decreased both the risk of all-cause (21 RCTs, 18,781 patients, RR 0.81, 95% CI 0.74, 0.89) and cardiovascular deaths (20 studies, 18,746 patients: RR 0.80, 95% CI 0.70 to 0.90). Statins decreased 24-hour urinary protein excretion (6 studies, 311 patients: MD -0.73 g/24 h, 95% CI -0.95 to -0.52), but there was no significant improvement in creatinine clearance - a surrogate marker of renal function (11 studies, 548 patients: MD 1.48 mL/min, 95% CI -2.32 to 5.28).The incidence of rhabdomyolysis, elevated liver enzymes and withdrawal rates due to adverse events (well known complications of statins use), were not significantly different between patients receiving statins and placebo.

Authors' conclusions:

Statins significantly reduced the risk of all-cause and cardiovascular mortality in CKD patients who are not receiving renal replacement therapy. They do not impact on the decline in renal function as measured by creatinine clearance, but may reduce protein excretion in urine. Statins appear to be safe in this population. Guidelines recommendations on hyperlipidaemia management in CKD patients could therefore be followed targeting higher proportions of patients receiving a statin, with appropriate monitoring of adverse events.

This record should be cited as:

Navaneethan SD, Pansini F, Perkovic V, Manno C, Pellegrini F, Johnson DW, Craig JC, Strippoli GFM. HMG CoA reductase inhibitors (statins) for people with chronic kidney disease not requiring dialysis. Cochrane Database of Systematic Reviews 2009, Issue 2. Art. No.: CD007784. DOI: 10.1002/14651858.CD007784

Assessed as up to date:

April 2, 2008

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Primary Review Group:

Renal Group

Health topics:

Kidney disease > Chronic kidney disease > Cardiovascular risk management

Cochrane Summaries^beta

Independent high-quality evidence for health care decision making

Statins cause a significant reduction in the risk of all-cause and cardiovascular mortality in CKD patients who are not requiring dialysis

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